? BRAINs Bundle Regular of AMSA-Indonesia National Competition
Indonesian Medical Students’ Training and Competition (IMSTC) 2015 26 February - 1 March 2015
Our society needs more heroes who are scientists, researchers, and engineers. We need to celebrate and reward the people who cure diseases, expand our understanding of humanity and work to improve people’s live.
Mark Zuckerberg
BRAINs
Bundle Regular of AMSA-Indonesia National Competition
Indonesian Medical Students’ Training and Competition (IMSTC) 2015 Edition
Steven Philip Surya Editor in Chief Dea Firstianty Hendrawan Tifani Sutrisno Pinka Nurashri Hasbi Alicia Sandjaja Kevin Sastra Dhinata Nurul Fadhilah Auliya Ananda Editor(s)
Jevonda Edria Bamitha Emiliana Kartika Cover Design
Contents Scientific Paper Video Scientific Poster Public Poster Photography
? Scientific Paper
LITERATURE REVIEW Adult Care Centers (ACCs) as a Solution to Maintain and/or Improve the Physical Function (Activities of Daily Living and Instrumental Activities of Daily Living)of the Elderly in Indonesia Gerry Wino1, Fidia Tania1, Steven Philip Surya1 1
Faculty of Medicine, Atma Jaya Catholic University of Indonesia (AMSA-UAJ) Abstract
As the life expectancy rises, Indonesia is facing the problem of increasing number of elderly people. The status quo is either taking care of the elderly at home or admitting them into nursing homes. Home cares services fail in maintaining the physical function (IADL/ADL) which corresponds to the quality of life. The idea of nursing homes is still considered as a taboo by the general population and is financially costly. Adult Day Centers (ADCs) is seen as an alternative to counter the problems and help sustain the physical function of the elderly, thus their quality of life. The study is a literature review of various journals retrieved from Google Scholar with keywords of
“IADL”, “ADL”, “physical function”, “home care
service”, “day care center” and “elderly people”. ADCs provide the physical and social requirements needed in order to maintain the physical function (IADL/ADL) and quality of life of an elderly. It eliminates the stress of caregivers, decreased service time and minimizes the risk of falling, all three are found in home care services. Furthermore, ADCs encourages caregivers-recipients relationship. Elderly people who attend ADCs are found to have higher score of IADL/ADL compared to their peers in home care. ADCs is an alternative which the Government needs to provide in order to maintain the quality of life of the increasing elderly population through sustaining physical function. Keywords: IADL, ADL, elderly people, Adult Day Center, physical function
Introduction Indonesia is considered to be a developing
Aging is defined by Merriam Webster as
country. As the nation is still developing,
“Gradual change in an organism that leads
so are the people. Along with the success
to increased risk of weakness, disease, and
of the government in increasing the GDP
death. There is a decline in biological
income of the population, building better
functions and in ability to adapt to
education and providing better access to
metabolic stress. Overall effects of aging
health care, the people’s quality of life also
include reduced immunity, loss of muscle
increases. As the people’s quality of life
strength, decline in memory and other
increases, so is the life expectancy. Life
aspects of cognition, and loss of colour in
expectancy is one of the indicators to
the hair and elasticity in the skin.” (“Aging
measure how successful a Government is
- Definition and More from the Free
in providing health care programs. The
Merriam-Webster
higher the life expectancy of the elderly in
n.d.)Anelderly person is someone who has
a country, the better the quality of life it
reached 60 years of age, as described by
provides and the more successful the
both the World Health Organization
Government is. Hence, a developing
(WHO) and Badan Kependudukan dan
country is going to deal with the increasing
Keluarga Berencana Nasional or BKKBN
life expectancy which results in more
(National
elderly people.
Planning Agency). By the time they reach
According to KomnasLansia (National
the age of an elderly people, their body
Commission for the Elderly), the number
would have gone through a lot of wear and
of elderly people in Indonesia is expected
tear process that is consistent with the
to reach 28.8 million people (11.34% of
theory of aging. This would then create the
the population). (“Komisi Nasional Lanjut
problem of decline in physical conditions
Usia - Komnas Lansia - Lampu Kuning
caused simply by the inability of the body
Ledakan
n.d.)Life
to regenerate or create needed parts that is
expectancy rises from 64.5 in 2000 to 67.4
injured or by diseases and infection. As a
in 2010 and is predicted to reach 71.1 by
result, elderly people are at risk of having
2020. (“Artikel | BKKBN,” n.d.)This
physical inability. Another factor would be
poses problems towards the Government,
the risk of falling, which is very common
the population and mostly to the care of
in elderly people. In addition, mental and
elderly people.
cognition decline (such as Parkinson’s,
Kaum
Renta,”
Demographic
Dictionary,”
and
Family
Dementia and Alzheimer) might take part
doctors and nurses to cope with the
in the declining physical function in
medical conditions of the patients. In
elderly people.
addition, ADCs provide the much needed
Since the population of elderly people is ever growing, the Government has to come up with a solution on how to care for the elderly in order to provide a good quality of life despite all the problems that they are having. Nowadays, there is a debate on how
the
younger
socialization
among
elderly people. They can get along with their peers in various activities designed to sustain their physical function. (Schmitt, Sands, Weiss, Dowling, & Covinsky, 2010) Since the function status of the elderly is
Government should care for the elderly
one of the important factors in determining
people. Some elderly people are taken care
the quality of life, it is essential to be able
by their family (spouse and/or children)
to measure the degree to which they are
while others are admitted into nursing
capable of functioning. The Activities of
homes. Another alternative is to provide
Daily Living (ADL) and Instrumental
Adult Day Centers (ADCs), which is quite
Activities of Daily Living (IADL) are
popular in developed Western countries.
developed to measure the functional status
Adult Day Centers is accepted and
of a person. ADL is first developed by
integrated components of a community-
Katz to assess the rehabilitation potential
based system of service for the elderly.
of
Established nearly 50 years ago, Adult
consists of questions regarding the ability
Day Service (ADCs) centers provide
to do basic activities such as walking,
outpatient support services to help older
bathing,
adults with functional limitations remain in
brushing teeth and eating. IADL was first
the community and reduce caregiver
developed by Lawton and Brody to
burden. The purpose of ADC is to
facilitate
maintain or even improve the functional
professional and patient regarding the
status of the care recipients though health
patient’s potential to support his own
services and social interactions adjusted to
independent lifestyle, among others are
the individual functional level. ADCs
cooking, driving, using the telephone or
provide
perspectives:
computer, shopping, keep track of finances
physical, social and psychological. ADCs
and managing medications. When an
employ medical professionals such as
elderly person scores high in their
in
three
and
for
the
care
people
opportunity
hospitalized
getting
geriatric
dressed,
communication
patients.
It
toileting,
between
IADL/ADL scale, they are considered to
intervention
in
form
of
medication,
be high functioning elderly who are still
lifestyle intervention and race specific
capable of doing the activities. This is
researches. From the search, we found at
directly proportional with their quality of
least 20 publications that are relevant to
life. Hence, the physical functional status
our study. Then, we integrated the
of an elderly affects the quality of life, and
materials from various publications which
vice versa.
is relevant to our study.
The purpose of this study is to compare and determine which care is most the most efficient and effective model and to give
Results
suggestions on future planning towards the
From the study, we can conclude that the
care of elderly people. The objective is to
elderly people who live in Adult Day
provide information of ADCs and why it is
Centers (ADCs) are found to have better
better compared to home care services. In
quality of life compared to those living
addition,
the
under home care. The explanation lies on
correlation between physical function
the concept of the ADCs which focuses on
(IADL/ADL) and quality of life.
community
this
study
provides
based
living.
Orientation,
Memory and Concentration scale (OMC) Methods
is
The method used is literature study of
IADL/ADL scores. High score in OMC in
international
correlated
journals
to
find
the
directly
proportional
with
the
high
with score
the in
differences of physical function score
IADL/ADL. The high score of OMC in
(IADL/ADL) between elderly population
sample elderly population is provided in
living in ADC and at home.
Table 1. In Table 2, the IADL scale of sample elderly population living in a
Search engine used is Google Scholar with
community shows perfect score (5 out of
the keywords: “IADL”, “ADL”, “physical
5) in terms of housekeeping ability and
function”, “home care service”, “day care
transportation usage. Following with good
center” and “elderly people”. The time
or near perfect score (4 out of 5) are
range of publication of these journals is 20
activities such as telephone usage, meal
years span from 1994 to 2014. From the
preparation and shopping. The elderly
search,
scholarly
score average (3 out of 5) in activities such
publications. The exclusion criteria are
as laundry, medication taking and financial
we
found
4,150
handling. (Cromwell, Eagar, & Poulos,
function of the elderly declines. This can
2003) In contrast, the elderly people who
be seen in the low IADL/ADL score found
receive home care have lower IADL/ADL
in those elders.
score compared to the elderly in ADCs.
Furthermore, the capacity of informal caregivers in providing medical assistance, social
interactions
and
psychological
assessment is doubtable. This is because We have identified three major problems
most of them are not equipped with the
that cause the low IADL/ADL score in
knowledge on how to deal with elderly
home care elders: decreased number of
patients. Simply put, most of them are not
service time, lack of opportunity to
trained professionals in dealing with the
socialize and the risk of falling. In home
various yet important needs of the care
care, there are two known category of
recipients. The quantity of time spend in
caregivers: formal and informal. Formal
taking care of the elderly does not
caregivers are professionals (doctors or
necessarily mean better outcome for
nurses) who are hired to take care of the
studies have shown how quality far
elderly in form of home visitation.
outweigh the quantity of time spend in
Informal caregivers consist mainly of the
elderly
family of the care recipient. Family plays
providing formal care and equipments to
the most important role in home care
improve the medical condition, the elderly
service since the amount of time they
population living under home care is still
spend far surpass that of formal caregivers.
vulnerable
The problem with informal caregivers is the huge tendency to be overload and develop stress. Compared to the caregivers in ADCs, informal caregivers have higher
care.
Despite
to
the
developing
effort
in
medical
conditions, diseases and infection. This is because
the
varieties
of
equipments
available are considered low or incomplete compared to the ones provided in ADCs.
degree of depression. This condition
From social perspective, elderly people
causes decrease in the quantity of service
who live at home tend to have low social
time. As mentioned above on how the
life compared to their peers who stay in a
informal caregivers play a huge part in
community. An explanation would be that
home care service, the impact caused is
since the informal caregivers are family
considered to be major. As the result of
who are much younger (mostly children or
unmet amount of service time, the physical
even grandchildren of the elderly), there is
a
generation
gap
that
restricts
may not be carried out due to the lack of
communication between the caregiver and
knowledge on how to properly do it.
the recipient. The reason why elderly
Hence, elderly people at home have higher
people who participate in ADC do not
prevalence of falling in the toilet.
have this problem is because they are gathered based on age. Their peers are of the
same
age
or
have
slight
age
differences. Since they grow up in the same era, there are more things they can relate to. Psychologically, the more things they have in common, the stronger bond they form. Generation gap is minimized or even
diminished.
Furthermore,
the
presence of peers provides motivation for the elderly people since they feel accepted in the group. (Morris, Sherwood, & Morris, 1996)
In addition, elderly people living at home have a high prevalence towards bad lifestyle which includes, but are not limited to smoking, alcohol consumption, fast
food
consumption
and
obesity,
inadequate intake of fruits and vegetables and physical inactivity. As seen in Figure 1, there are 12.4% smokes, 65% are obese and
and
5.3%
consumes
alcohol.
Approximately 40.5% consumes fast food and 83.1% have less vegetables and fruits diet. The prevalence of physical inability in the group is 48.5%. As a result of
The high risk of falling is a risk factor of
unhealthy lifestyle, 25.2% of the sample
physical inability in adults. It is considered
suffers from severe limitation and 15.7%
to be the reason of most physical inactivity
suffer some limitation. This limitation
of elderly people. Most falling incident
contributes to the physical function which
occurs in the toilet. The elderly receiving
can be seen in the IADL/ADL score. There
home care services have higher is of
are also other risk factors that decrease the
falling compared to their peers in ADCs.
physical function as seen in Figure 2.
This is due to the purpose of ADCs is to
(Kim, Sagar, Adams, & Whellan, 2009)
provide care for elderly people that they are adjusting to their needs in building the
Discussion
Furthermore,
ADCs
hire
The purpose ADCs is to increase the
workers
who
are
quality of life of both the elderly people
professionals in toilet management. Proper
and the caregivers. The quality of life
toilet cleaning procedure is conducted in
consists of physical function (IADL/ADL),
order to minimize the risk of falling. In
physical health, social networking or
home care, the correct toilet management
relationship and adequate health care
facilities. maintenance
service. A rise in the quality of life of the
the programs provided by ADCs have
caregivers
services
small or even no contribution towards the
towards the elderly people. A better care
health status and physical function of the
contributes to a better physical function
aged population. However, the programs
and can be seen in the high scores of
then did not focus on the social programs.
IADL/ADL.
To note, there are currently three models
results
in
better
In a study, health status and physical function status are shown to be the most important factors in the quality of life. The better the health status and physical function of a person, the better their quality of life is. Social networking and relationship
are
made
interactions,
social
up
support,
of and
social life
satisfaction. The living environment also contributes to the quality of life. It is
of ADCs: social model, specialized model and medical model. Social model is a model of ADC where they provide social services, nutrition and assistance in doing ADL. Furthermore, a study conducted in 2003 proves that social model, now provided by the ADCs, affects the physical function and health status. Home care services do not have social programs such as that of the ADCs. (Schmitt et al., 2010)
important to provide an environment with
ADCs focus on both the recipients and the
no barrier, as the limitation of activity
caregivers. It is important to pay attention
caused by this restrictions result in low
to the caregivers since the condition of the
physical activity. Hence, this will also
caregivers will affect the quality of life and
affect the quality of life. On the other
the physical function of the patients. In
hand, the degree of stress of the caregivers
ADC,
contributes to the quality of life of the
depression and overload due to the less
recipients.
are
time spent in redirecting their relative and
contributory to each other and have effect
assisting with activities of daily living as
towards the quality of life. The quality of
well as a decrease in role overload and the
life determines the physical function.
reduction in care-related stressors and an
All
these
factors
The key concept of ADC is to provide a community where the elderly people are
the
caregivers
have
lower
increase in caregivers’ ability to tolerate stress. (Schmitt et al., 2010)
respected and supported as a well being, as
In an interview carried out during a study,
well
their
the elderly people population pointed out
autonomy through a comprehensive model
that social networking and relationship are
program. In 1985, a study concluded that
important, especially in the form of
as
providing
them
with
supports. The elderly people are happy to
highly correlated with the functional status
have social contact and some of them
(IADL/ADL).
expressed their intention of not being a burden to their family, who are informal home caregivers. In that sense, ADCs provide the much needed opportunities to socialize with other people and alleviate the burden of the recipient’s family. This means that ADCs suits the need and intention of the elderly people found in the interview. In the same interview, the caregivers pointed out how they can also socialize with other caregivers. In addition to peer-to-peer communication, the ADCs act
as
media
for
patient-caregiver
interactions. An elderly person can discuss new topics and recent issues with their caregivers. As proven in how they embrace
physical
contact
(such
as
hugging) and emotional relationship, the increasing of quality of life and physical function (IADL/ADL).
The various activities that the elderly can participate in ADCs are important in training and maintaining their physical function. The activities involve outdoor activities, which main purpose is to sustain the physical function of the elderly. In comparison, home cares only provide activities restricted to indoor activities, which main purpose are not to sustain the IADL/ADL of the patients. Many elderly people acknowledge the significance of physical activity to have a healthy life. However, they dislike the idea of doing so. In a home care service, the ignorance of physical activities is not resisted enough, that the elderly can skip doing it. There is simply no other motivation to do so. However, the “challenge” of their peers, who are active physically active will ignite a friendly competition between aged
From the perspective of safety and
people. It is the nature of human
security, ADCs are safer compared to
competitiveness that drives the elderly
home care. One of the reasons is that they
who at first dislike physical activities to
employ
These
proof that they can also do physical
maintenance workers take better care of
activities that their peers can do. This will
the toilet rather than in home care. As a
help maintain or even increase the
result of better toilet maintenance, the risk
IADL/ADL of the elderly people. (Schmitt
of elderly people in ADCs’ falling in the
et al., 2010)
maintenance
workers.
toilet is lower than that of the patients of home care. Prevalence in risk of falling is
The
employees
of
ADC
are
also
professional in doing their job since they are paid. This will guarantee the warm
service given to the recipients. This
time.
condition creates a comfortable living
information and medical conditions that
environment for the elderly as well as
are important in assessing the IADL/ADL
keeping their autonomy intact. Elderly
of the elderly. A suggestion is to have an
people tend to stay in ADCs for the reason
integrated information sharing system
of
living
between both the caregivers in the ADC
environment and that because they enjoy
and the informal caregivers at home. The
their stay. This will result in better quality
synchronization
of life and hence, better physical function
medical conditions will provide a better
(IADL/ADL).(Molzahn,
field of examination to which a caregiver
their
independence,
good
Gallagher,
&
McNulty, 2009)
provides
of
a
breach
information
of
and
can weigh on before giving a certain
The living environment of the elderly is also very important. It is proven that elderly who spend their time in ADCs perceived lessened impact of physical and emotional
This
impairments
functioning
in
the
admission
in
ADCs.
on
year
everyday after
A
their
possible
treatment or designing various programs that suits the an elderly people individual needs. (Molzahn, Gallagher, & McNulty, 2009) The suggestion for the Government is build and/or ease the authorization of ADCs
construction
in
Indonesia.
explanation would be the various approach
Furthermore, the society can play a role in
of the ADCs suited to the needs of the
helping to change the stigma and build a
recipients. The personalized social and
good paradigm of ADCs. ADCs are now
physical environment makes the recipients
very popular in the Western countries
able to comfortably meet the demands of
because of the perception on how the
the environment. On the other hand,
elderly are not neglected and are actually
elderly people living at home experiences
living a better quality of life. In addition,
more problems in everyday functioning
we
because they are living in an environment
professionals to promote the importance of
where their competence cannot meet the
elderly care and ADCs to the general
demand of the environment. (Schmitt et
population. This can be achieved through
al., 2010)
seminars.
Since the elderly people spend only a few hours a day in the ADC, the caregivers cannot watch the elderly people all the
advise
the
For
primary
specialist
health
doctors,
care
we
suggest that they advise their patients to attend ADCs. Medical students can also take part in the caring of the elderly
through work or visitation to ADCs.
elderly in a nursing home is a taboo among
Another thing is the Government through
Indonesians. Most Indonesians still believe
the collaboration of Ministry of Research
that caring of the elderly is their
and Higher Education and Ministry of
responsibility and by sending elderly
Health
people
can
Gerontology
provide programs
Geriatrics for
and
graduate
programs. The current curriculum of
to
nursing
homes,
they
are
mistakenly thought to neglect the old people.
medical school integrates geriatrics and gerontology. However, higher education of the subject is rarely available. Conclusion
A third alternative is to provide Adult Day Center (ADC), which is asserted to provide solutions to problems posed by the
Life expectancy is one of the major
previous two alternatives. A unit to
indicators of the success of health care
measure the physical function is the
programs of the Government. Indonesia as
IADL/ADL score. Both are standardized
a developing country is facing the ever
and widely acknowledged in determining
increasing life expectancy. However, the
the capability of elderly people in carrying
rise of life expectancy causes a boom in
out simple basic activities and their
the number of elderly population. The
physical function.
classic problem that can be found in elderly people is the decline of physical function of the elderly. This is a burden of the productive population in a country.
Since the ADCs serves as a day care center for elderly people, the role of families at home are is effectively diminished but simply decreased. Firstly, ADCs rebutted
The current response to the problem is by
the idea of neglecting the elderly since the
taking care of the elderly at home or at
elderly only spend a certain amount of
nursing home. However, both options do
time in the ADCs. They will still stay with
not solve the main goal which is to
their families at home. Financially, ADCs
preserve or even improve the quality of
does not cost as much as the nursing
life of the elderly through maintenance of
homes. Lastly, ADCs provide a systematic
physical function. At home, the physical
and effective control of the elderly
function of the elderly is keeps on
people’s physical function and help sustain
declining. On the other hand, nursing
them through the various activities offered.
homes are costly and the idea of putting an
Further studies of the first two arguments
are advised. This study focuses on the
bad lifestyle such as smoking, alcohol
latter argument.
consumption,
The reason why this study excludes nursing home is that because the idea of nursing home is not widely accepted by the population. In order to prove the hypothesis, we did a literature review of international journals. The search engine we use is Google Scholar with inclusion and exclusion criteria mentioned earlier in the methods. From the literature review, the
Orientation,
Memory
and
Concentration scale (OMC) of the elderly admitted ADCs are high. The OMC is directly proportional to the IADL/ADL scale. Thus, the elderly population in ADCs has high IADL/ADL score. The score
for
housekeeping
ability
and
transportation usage is perfect. The elderly are
considered
good
in
using
the
telephone, preparing meals and shopping. They score an average in medication taking, laundry and financial handling. The
elderly
at
home
have
lower
IADL/ADL score than their peers in ADCs
vegetables
and
fruits
inadequate diet. The ADCs main concern is the quality of life of the elderly, where one of them is the physical function (IADL/ADL). References 1. Aging - Definition and More from the Free Merriam-Webster Dictionary. (n.d.). Retrieved December 19, 2014, from http://www.merriamwebster.com/dictionary/aging 2. Artikel | BKKBN. (n.d.). Retrieved December 19, 2014, from http://www.bkkbn.go.id/ViewArtikel.as px?ArtikelID=111 3. Cromwell, D. A., Eagar, K., & Poulos, R. G. (2003). The performance of instrumental activities of daily living scale in screening for cognitive impairment in elderly community residents. Journal of Clinical Epidemiology, 56(2), 131–7. doi:http://dx.doi.org/10.1016/S08954356(02)00599-1
because of the decreased number of
4. Kim, D. H., Sagar, U. N., Adams, S., &
service time, lack to opportunity to
Whellan, D. J. (2009). Lifestyle Risk
socialize and that they are at risk of falling.
Factors and Utilization of Preventive
The concept of home care service is
Services in Disabled Elderly Adults in
patient-centered. On the other hand, ADC
the Community. Journal of Community
uses both patient-centered and caregiver-
Health, 34(5), 440–8.
centered approach. In addition, the elderly
doi:http://dx.doi.org/10.1007/s10900-
living at home have the tendency towards
009-9166-4
5. Komisi Nasional Lanjut Usia - Komnas Lansia - Lampu Kuning Ledakan Kaum Renta. (n.d.). Retrieved December 19, 2014, from http://www.komnaslansia.go.id/module s.php?name=News&file=article&sid=2 6 6. Molzahn, A. E., Gallagher, E., & McNulty, V. (2009). Quality of life associated with adult day centers. Journal of Gerontological Nursing, 35(8), 37–46. doi:10.3928/0098913420090706-02 7. Morris, S. A., Sherwood, S., & Morris, J. N. (1996). A dynamic model for explaining changes in use of IADL/ADL care in the community. Journal of Health and Social Behavior, 37(1), 91–103. 8. Schmitt, E. M., Sands, L. P., Weiss, S., Dowling, G., & Covinsky, K. (2010). Adult Day Health Center Participation and Health-Related Quality of Life. The Gerontologist, 50(4), 531–540. doi:10.1093/geront/gnp172
Tables and figures
Table 1. The OMC score in the study shows high score of the elderly.
Table 2.The IADL table of the study shows high score of the elderly. The elderly score “perfect” in housekeeping and use of transportation, “good” in telephone usage, meal preparation and shopping, and “average” in medication taking, laundry and financial handling.
Figure 1.Prevalence of lifestyle risk factors by the degree of disability
Figure 2. Utilization of screening and preventive health services by the degree of disability.
LITERATURE REVIEW Robotics Exoskeleton for Physical Rehabilitation in Disabled Post- Stroke Geriatric Patient Sallie Naomi1, Cindy Kahono1 1
Faculty of Medicine, Atma Jaya Catholic University of Indonesia (AMSA-UAJ) Abstract
Stroke is an age related-disease. As the number of geriatric population and their life expectancy increase, therefore the stroke probability will also increases. From the current method of health care, the mortality number caused by stroke might decrease but the patient disability post-stroke still occurred. To obtain optimum recovery, intensive, and focus rehabilitation is needed. Due to this fact, the 21st century has currently offered robotics exoskeleton as a new method of rehabilitation for disabled post stroke patient that can fulfill the current needs in health care.The objectives of the study are to find the effectiveness and safety of robotic exoskeleton rehabilitation in post stroke geriatric patient. The study was conducted by systematic review, obtaining a total of 25 literatures (journals). Journals were selected from Proquest and EBSCO from year 2009-2014. Inclusion of the journals was the one conducting a research about geriatric, post-stroke, rehabilitation post-stroke and robotic exoskeleton.From the literature collected, we could see the study of robotic exoskeleton to be used as a physical rehabilitation in upper limb and lower limb (incl. ankle), programming method of robotic exoskeleton as a prove that it can be used to do physical rehabilitation, and the safety test of this product on disabled post stroke geriatric patient.The study conducted showing result that robotic exoskeleton in physical rehabilitation is acceptable to be used as a rehabilitation property (algorithms program success), cause a significant motoric improvement in patients (improvement in Jerk, strength, velocity, and motoric assessment chart), and also safely (no adverse effect occurred) used.
Robotic
exoskeleton is more effective as a rehabilitation method compared to the current conventional rehabilitation method and it is also safe to be used as a rehabilitation property in disabled poststroke geriatric patients. Keywords: geriatric, robotic exoskeleton, post-stroke, physical rehabilitation
Introduction
follows(BĂŠjot et al., 2010; Jak et al., 2009;
Every year, 15 millions people worldwide
Vieira, Freund-Heritage, & Costa, 2011):
suffered from stroke and up until this year
o
Ischemic
strokes
from
(2014) the number of stroke patients keep
lipohyalinosisof
increasing
cases/year).
arteries or lacunar infarct
Stroke itself is an age related disease (80%
(LACI) defined as a stroke
of the patients are >65h years old), because
presenting
its incidence typically increases within age
classical lacunar syndromes
and aging of the population, or commonly
and confirmed by a small
named as geriatric stroke. Due to this record,
(<15
the prevalence of stroke in the future is
subcortical infarct on brain
likely to increase by the increment of aging
CT scan or MRI
(Âą800.000
new
mm
small
one
in
of
the
diameter)
population. WHO through the global burden
o Ischemic stroke from cardiac
of stroke campaign stated that one in six
embolism (CE) due to either
person worldwide will experience stroke in
atrial
their lifetime. (Carod-artal, Ferreira Coral,
diagnosed on EKG or Holter
Trizotto, & Menezes Moreira, 2009; Eijk et
EKG
al., 2010; Lee, Weng, Wu, & Wu, 2010)
fibrillation
o Spontaneous
(AF)
intra-cerebral
hemorrhage = SIH
Stroke
o Subarachnoid hemorrhage =
Stroke is a condition of a sudden death of
SAH
brain cells in a localized area due to
Stroke often results in impaired motor
inadequate blood flow. Its risk factors are
control and persistent weakness, which also
hypertension,
called the leading cause to chronic disability
diabetes
hypercholesterolemia,
alcohol
mellitus, intake,
(e.g.:
walking
and
balance
function).
history of transient ischemic attack, previous
Disabilities that might occur are, persistent
myocardial infarction, hypertensive, smoker,
lower limb (LL) and/or upper limb (UL)
obese, and peripheral vascular disease.The
weakness from hemiparesis that often results
classification of stroke subtype used since
in functional motor deficits. Hemiparesis
1985 in the Dijon Stroke Registry is as
(HP)
gait,
compounded
with
balance
deficits, limits mobility and increases fall
risk, with nearly 70 percent suffering fall-
The current management for disabled post
related injuries in the first year post-
stroke geriatric patient is through veteran
stroke(Adey-Wakeling & Crotty, 2013).
health
While UL impairments limit the patient’s
method),
activity in daily living and may lead to
occupational therapists, physical therapists,
permanent disability. The impairments are
kinesiotherapists, recreation therapists, and
typically characterized by weakness of
speech and language pathologists (Cifu,
specific muscles, lack of mobility between
2010). Nowadays, there are several method
structures at the shoulder girdle, incorrect
conducted to rehab disabled post-stroke
timing of components within a movement
patients
pattern and loss of interjoint coordination.
rehabilitation. But, the result from this type
This disability could further affect the
of rehab is that 35% of stroke patients
skeletal muscle fiber composition (type II
admitted that they couldn’t be dicharge to
decrease), muscle atrophy, loss of skeletal
independent living situation, because there’s
muscle cross sectional area, that will lead to
no sign of health increment. (Eijk et al.,
decrease in function and mobility(Sions,
2010).
Tyrell, Knarr, Jancosko, & Binder-Macleod, 2012). Other than disability, depression might also occur post-stroke, that is mainly caused by patient disability to afford activity of daily living and also a decrease in life quality. Depression itself could slow down the recovery rate of the patient, as until now the management for this post-symptoms are treated using anti depressant (medication), because the placebo doesn’t seem to generate positive effect (Mikami et al., 2011). Current Management
administration consist
such
as
(conventional
of
physiatrists,
nursing
homes
The prove that stroke health care has been improved can be seen through the mortality rates that have been decreasing although a large number of patients still remain disabled regardless of the time that has elapsed post-stroke. 12% of the patients with stroke are independent in basic activities of daily living (ADL)while around 25–74% of patients have to rely on human assistance for basic ADLs like feeding, self-care, and mobility.(Veerbeek et al., 2014) Current Problem and Advanced Problem Management
Current problem arised related to geriatric
Ways to solve this problem is to find
stroke from the patient and health care
effective and reliable ways to restore motor
perspective is that, most of geriatric stroke
control, promote faster and greater recovery
patient do not do not participate in intensive
that may help or even relieve the disability
rehabilitation programs. This is probably
caused by stroke. There is evolving evidence
caused by the current rehab method that is
that patients canregain motoric function for
not effective enough to encourage patient to
extended periods after their onset because
follows an intensive rehab program (Saleem,
the plasticity of the cerebral cortex enables
Khalid, & Qidwai, 2009). Second, geriatric
areas of the brain to be reassigned the
stroke patients are greatly underrepresented
control tasks.This could be attained by
in outcome studies and the successfulness of
interdisciplinary
their rehabilitation are still unknown (few
physical therapy which is primarily aimed at
clinical research about geriatric, including
restoring and maintaining ADLs, usually
the efficiacy of exoskeleton as post stroke
starting within the first days and often
treatment). Third, impairment also lead to
continuing into the chronic phase post-
significant limitations in performing basic
stroke.The 21st century technology which is
activities of daily living, which negatively
robotics exoskeleton are surely a reliable
affect these individuals ability to participate
and promising to use as a modern rehab
in community life. Fourth, due to the
treatment through motor learning. A robotic
increase in health care cost and a big amount
exoskeleton is a robot designed so that it can
of money needed to treat stroke, length of
be worn in human body with parts and joints
stay and quality of the treatment becomes an
similar to human body. Motor learning (ML)
important matter to patient (Sommerfeld et
principles that are now widely accepted as a
al., 2011). Fifth, the current conventional
modern basis for effective rehabilitation.
rehabilitation
(manual-therapist
Compared with a human therapist, robots
assisted) increases the falling probability
allow for massed repetitive practice of
(either due to patient condition or inadequate
affected limbs and can provide therapists
facility) in therapy that could lead to a
with a variety of practice conditions that can
worsen patient condition (Campbell &
be tailored to the needs of individual
Matthews, 2010; Nanda, Dey, Gulstrand,
patients. With rehabilitation goals focus on
Cudnik, & Haller, 2011; Vieira et al., 2011).
mobility, as mobility is strongly correlated
method
stroke
rehabilitation
is
with independence. In fact, besides using
rehabilitation,
robotics exoskeleton for rehab, it also can be
exoskeleton rehab in the outcome of
used as a neural prostheses (series of devices
disabled geriatric patient. The results from
that can substitute a motor, sensory or
the literature search were firstly reviewed by
cognitive modality that might have been
reading the titles and abstracts by two
damaged as a result of an injury or a
independent reviewers. The relevant studies
disease).(Jung, Jang, Riener, & Park, 2012;
were further checked by reading the full
Ommaya et al., 2013; Roy, Forrester, &
texts and assessed for inclusion.
Macko, 2011; Veerbeek et al., 2014)
and
(2)
the
effect
of
The review team was recruited from the
The objectives of this study areto know the
AMSA-UAJ. Citations were included if they
effectiveness of robotic exoskeleton in
met criteria listed above resulting in a
disabled post stroke geriatric patient and to
preliminary set of 25 potentially relevant
know the safety of the robotic exoskeleton
publications. The full text articles were
use in rehabilitation post-stroke program.
electronically distributed to the review team along to be summarized. Two reviewers
Methods A
systematic
extracted information independently related literature
search
was
to
study
design,
study
population,
conducted with databases in Proquestand
interventions, outcome measures, methods,
EBSCO for articles published between 2009
results, and conclusions for each article.
until 2014. We used the following terms in
Results were compared and reevaluated in
the search field: Stroke AND [Geriatric],
group sessions until consensus was obtained
Stroke AND [Risk Factors], Exoskeleton
between reviewers. The final analysis
AND [Geriatric] AND [Stroke}. The search
included 25 articles, which met the criteria
results were downloaded into a personal
for the present review.
database. The results from Proquest and EBSCO were then combined, and duplicate publications were eliminated.
The primary outcome used in this systematic review
was
the
motoric
improvement
(speed, Jerk, strength, time, number of task
The inclusion criteria used in this systematic
completed
review were the following: (1) study
assessment chart. The data were extracted
representing
from
geriatric,
stroke,
and
the
during included
rehab)
and
studies;
motoric
the
main
information included first authorâ&#x20AC;&#x2122;s name,
Verifying the robotics exoskeleton will be
publication year, methods of treatments,
completed with several steps, mentioned
number of patients, and overall assessment.
below:
Result
1) The subject wearing the exoskeleton starts standing.
Robotics Exoskeleton Design The design and program of the robotic exoskeleton are vital to enhance and optimize the quality and efficiency of the robotic exoskeleton. Several things that are
2)
The
subject
moves
the
crutches
simultaneously so that the tips of the crutches are located in the marked position on the ground.
important to consider in building the robotic
3) The subject maintains his standing
exoskeleton are the algorithms programming
posture by distributing his weight to his
and similarities to the human anatomy.
crutches and feet.
Algorithms programming are essential for the
functional
and
movement
system,
position and force sensor of the robotics
4) In order to start walking, the subject moves his mass center to the opposite legs.
exoskeleton, also as a proof that this
5) The robot detects this movement and
exoskeleton are applicable to be used as a
starts walking.
rehabilitation method.
6) The subject repeats steps 2 to 5.
The algorithms and design are tested with LL
robotics
exoskeleton
through
this
(figure 1, figure 2)
procedures (Jung, Jang, Riener, & Park,
Algorithms
2012):
Exoskeleton(Jung et al., 2012)
1) Verifying robotics exoskeleton with a
(table 1)
non-handicapped person.
Upper
Test
Limb
on
(UL)
LL
Robotics
Rehabilitations
2) Verifying a walking intent detection
Program (Frisoli et al., 2012; Grimaldi &
algorithm with a paraplegic patient.
Manto, 2013; Milot et al., 2013) The UL rehabilitation study program is conducted with twenty subjects (53-67 years
old) with mild to moderate chronic stroke.
ranges of motion are used for this study in
Each subject is assigned to a multijoint
both multi/single-joint training.
functional and single joint training three sessions per week, for four weeks. The primary outcome measure was assisted using Box and Block Test (BBT). Secondary outcome assessment will use the FuglMeyer Arm Motor Scale (FMA), Wolf Motor Function Test (WMFT), Motor Activity Log (MAL), and quantitative measures of strength and speed of reaching. The assessment was takenbefore and after training period with a 3-month follow-up evaluation session.
The
single
joint
trainingconsisted
of
movementsat each of the four joints (shoulder, elbow, forearm and wrist—one at a time), with 10x repetitive and will be repeated for 6 times over the 60-minute training session. While the multi joint robotic training consisted of 40 minutes of computerized games simulating functional activities (catching a baseball, driving a motor cycle, shooting targets, dropping marbles down a pegged board, playing air hockey, making an omelet, dunking a
Subjects were randomized to receive either
basketball, and tracking a moving target
multijoint functional robotic training or
(pursuit rotor game)) and 20 minutes of the
single joint robotic training first and training
single joint robotic training. The games
was conducted 3X/week for 60 minutes per
required the coordination of multiple joints
session. After four weeks of training, and a
of the affected upper limb, including hand
week break, the subjects switched to the
grasp.
other training program. A trained physical therapist supervised each training session.A pressure powered arm robotic exoskeleton named
“Biomimetic
Neurorehabilitation
of
Orthosis the
for
the
Elbow
and
Shoulder (BONES)”that allows movement at the shoulder (flexion/extension, horizontal abduction/adduction,
external/internal
rotation), and elbow (flexion/extension), allowing the arm to move through normal
Other
assessment
of
the
kinesiology
performance (movement time, smoothness of motion) was analyzed in relation to the changes in the EMG pattern of muscle. The signals will be able to detect medical abnormalities, recruitment
activation
order
or
to
level,
or
analyze
the
biomechanics of human movement. EMG signals were acquired from four muscle groups, involved in elbow flexion/extension,
triceps brachii (TB) and biceps brachii (BB),
(visuomotor tasks). While the whole LL
and in shoulder extension/flexion, anterior
rehab program uses gait rehabilitation robot
deltoid (AD) and posterior deltoid (PD). The
named “LOPES”, by doing a walking task
activity
on a treadmill with gradually decreased
was
obtained
using
standard
Ag/AgCl bipolar surface electrodes (10 mm diameter). Electrodes were positioned over the border of the distal third of the muscle halfway between the innervations zone and the distal tendon parallel to the muscle fibers according to SENIAM guidelines.
Anklebot Training Result(Roy et al., 2011) (figure 5) Safety, Feasibility, and Reward Test on Robotic
(figure 3) Upperlimb Training using BONES(Milot et al., 2013)
Exoskeleton
Rehabilitation
(Goodman et al., 2014; Nilsson et al., 2014) The
(table 2) Lower
robot assistance.
safety
and
feasibility
test
were
conducted with subjects (median age:56) Limb
(LL)
Rehabilitations
with time from stroke 35 days after onset.
Program (Koopman, Asseldonk, & Kooij,
Training using robotic exoskeleton, assisted
2013; Roy et al., 2011)
by therapist, devices used to support gait
The ankle rehabilitations program included 7 participants (Age: 63.7±10.5)with chronic stroke with complete left/right hemiparesis and 7 non-disabled volunteers as control. The program uses anklebotfor an hour, for a total of 560 movement repetitions in dorsiflexion/plantar flexion. Task difficulty was adjusted to ankle range of motion, with robotic assistance decreased incrementally across training. Anklebot is interfaced with computer games "played" by moving the ankle in DF/PF and INV/EV ROMs
training
after
stroke
include
treadmill
training with or without body weight support (BWS). The robotic exoskeleton system comprises two subsystems for (cybernic) voluntary control (CVC) and (cybernic) autonomous control (CAC). Both modes activation is depend on the user’s intention. The CAC mode utilizes voluntary weight shift to initiate gait cycles and then provides predefined movements. While gait in the CVC mode continuously use input from voluntarily activated gait muscles to provide
support by the exoskeleton. The mode
leg and foot joint); moderate discomfort of
activation is done by the recordings of the
tight straps and the feeling of being trapped
bioelectrical signals that generated during
(n = 1), discomfort from shoulder straps (n =
muscle activation. Surface electrodes are
2); sense of the suit being heavy over the
placed over lower extremity extensor and
lower back (n = 1); temporary skin
flexor
are
irritation/redness from electrodes (n = 2;
incorporated in the control algorithm. It is
disappeared after finishing HAL training);
also equipped with a sensing system to
moderate pain in the groin after a HAL
receive input from potentiometers that are
training session (n = 1) (related to chafing
mounted on each joint and used as angular
from the harness); chafed feet due to wrong
sensors to measure the joint angles, from
shoe size (n = 1) (manage by change of
force-pressure sensors in the shoes and from
shoes); slight risk of stumbling due to
a gyro sensor and an acceleration sensor, to
impaired weight shifting occurred from time
determine the robot posture.
to time (support by two therapists was
torecord
the
signals
that
For the reward mechanism, it works by dividing subjects into 2 groups, high reward and low reward. The high-rewards group receives
monetary
reward
for
every
increment, encouragement, and daily score. The low-reward group receives none of the above. The assessment was done using anklebots
and
visuomotor
tasks
(gate
passage) and by comparing the change of increment in both groups.
needed). One patient reported pain in the paretic arm during training. (table 3) Discussion The
robotics
exoskeleton
works
by
recognizing the user intent belonging to human-robot interaction. It is a method for the exoskeleton by using its sensor system to recognize the instructions of the user from the userâ&#x20AC;&#x2122;s behaviors, neural signals, or thoughts.User intent recognitionis divided
No serious adverse events occurred. Minor
into two aspects: correct behaviors and
and temporary side effects comprised pain
correct time. Due to difference behaviors of
due to pressure from the cuff over the knee
walking in disabled patient, a different
(n = 1; managed by changing the height of
approach is used. The robotis able to assist
the cuff) and over the malleolus (n = 1;
paraplegic patients in walking with new
managed by changing the angle of the lower
approaches. To detect a userâ&#x20AC;&#x2122;s intent, forces
in each foot are measured by Floor Reaction
on the ground, this condition
Force (FRF) sensors. Second, to estimate the
is verified as true.
robotic exoskeleton posture high-resolution
•
Foot On: When each foot of
encoders are attached to each active joint.
the robot is on the ground,
After the algorithms has been developed, it
this condition is true.
is important to determine the behavior
•
Mass Center Shift Detection:
corresponding to each algorithm program
This
that had been associated with the user intent.
detection
start walking after moving their mass center shift detection (=True) and it corresponds to the concept of the walking intent detection algorithm by developing a similar walking method for paraplegic patients. Analysis of normal walking is conducted, whereas there
result
is
the
of
the
movement of a user’s mass
Based on the algorithms test result (Table 1), we can see that the robotics exoskeleton
condition
center. The same results occurred to the second experiment with the paraplegic patient. This data then suggests the effectiveness of the advanced algorithm. The paraplegic patient commented that the robot reacted quickly and precisely to his intent.
are 2 states: stance and swing, that occur
From the study above, we could tell that
simultaneously and three behaviors: first
robotic
step walking, continuous step walking, and
rehabilitation for hemiplegic or paraplegic
final step walking. Using these unit-walking
patients. So, these patients could become
behaviors, we can defined the states which
independently mobile again using a robotic
described the condition of the robot,
exoskeleton and enhancing the quality of life
described as below:
of the disabled patient.
•
•
exoskeleton
can
be
used
as
Crutch on: condition denotes
Training with the robotic exoskeleton from
whether or not the weight of
(Table
the user is distributed to the
improvements in the BBT, FMA, WMFT,
crutches.
MAL, shoulder and elbow strength, and
Crutch Off-On: When the
reaching speed and these improvements
user
crutches,
were persistent at the 3-month follow-up. A
moves forward, and pushes
significant decrease in the time to complete
raises
the
2)
resulted
in
significant
the task givencan be seen at the assist 3
the study (Assessment 4).It can be said that
column. For the strength assessment, a
UL robotic training had a significant and
meaningful increase in maximal voluntary
positive impact on the use and quality of
concentric strength was noted for the
movement of the trained upper limb as self-
shoulder adductors, shoulder internal and
reported by subjects during their ADL
external rotators, elbow flexors, forearm
performance. This study further supports the
supinatorand wrist extensors.
use of high-intensity and repetitive robotic
Evaluating the patient satisfaction, when asked if they enjoyed training on the robot, all subjects rated 5/5. When asked if they noticed any improvement in the motion of their affected limb, 44% of them rated 4/5 and 38% 5/5. More subjects rated 5/5 (41%) when asked if the gains obtained after the robotic training translated to improvement of daily activities.One of the subjects said â&#x20AC;&#x153;My left [affected] arm can now help me to wipe and wash my face, before BONES I could barely use my hand [affected] but now I can flip pancakes for my daughters and grandsons.â&#x20AC;? 6% of the subjects wrote that
exoskeleton training not only to reduce motor impairment but also to enhance motor function
post-stroke.
Second,
robotic
training likewise produced positive effects in
movement
execution,
other
than
decreased execution time, it also improved movement smoothness and increased active joint ranges of motion.Smoothness of a movement is an outcome of studied and coordinative
process
of
neuromuscular
system. The observed reduction of the movement irregularity indicates a better motor
control,
a
more
appropriate
recruitment of agonists and antagonists.
they preferred the single joint robotic
In LL rehab programs, the strategies used
training over multijoint functional robotic
also vital to enhance short-term skill
training, 19% multi- joint functional robotic
acquisition or retention, such asdeveloping a
training over single joint robotic training and
modular impedance-controlled ankle robot
75% rated both trainings equally.
(anklebot)
The results shows that BONES training is effective to improving the motoric of the affected upper limb, and that the gains were maintained after 3 months of completion of
to
deliver
task-specific
locomotors training aimed at improving paretic ankle contributions to walking and balance function after stroke.The anklebot allows effective training of the LL motor skill that is essential to restore the motor
function and implies achieving a level of
From the safety side, it could be stated that
performance in a given task. The anklebot
the robotic exoskeleton program did not
has two degree-of-freedom (DOF) and
cause any adverse events regarding to the
capable of actuating the ankle joint in
patient health. The problems occurred was
dorsiflexion-plantar flexion (DF/PF) as well
minor and technical due to incompatible
as inversion-eversion (INV/EV) ranges of
size. But the problem didnâ&#x20AC;&#x2122;t affect the
motion (ROMs). Active participation from
patient safety and problems could be solved
the patient is also important to facilitate the
by adjusting size and pressure afterwards. It
recovery process, where robotic devices
can also be stated from the data (Table 3)
control the interaction forces by using
that reward given to patient in post-stroke
impedance or admittance control algorithms.
rehabilitation program produce greater but
They guide the leg by applying force rather
not significant increment than patient in low
than imposing a trajectory.
reward group. So, encouragement and daily
The increased motoric function (figure 5) indicatesshort term motor adaptation in these variables. In contrast, the nondisabled group did not significantly improve in any of the motor control variables at the end of training. Importantly, the performance gains in all motor control metrics made by both groups at the end of training were retained at 48 hours as evidenced by the lack of statistically significant differences between the two time points, indicating short term motor learning. Although the use of anklebot are effective to increase LL motor
evaluation is quite an essentiall matter to support patient health . Conclusion It can be concluded that using robotic exoskeleton is more effective than the conventional usual care in hospital or nursing homes. The robotic exoskeleton rehab program effects are also significant if compared to the pre treatment. From the study, it can be said that robotic skeleton is also more safe and reliable than the current rehab method.
function, this rehab program can take weeks
For the further research, we would like to
to months, and proficiency can diminish
see the effect of robotic exoskeleton as a
over time in the absence of continued
neural prostheses in permanent disabled
practice.
geriatrics that might be possible using
cortical neural signal that will be translated
5.
by the device to produce movement.
Rehabilitation Services in the Veterans
X.
(2010).
Geriatric
64–73.
1. Adey-Wakeling, Z., & Crotty, M. (2013). Upper limb rehabilitation following stroke: current evidence and future perspectives. Health,
9(6),
629–647.
doi:10.2217/ahe.13.67
Osseby, G.-V., Durier, J., Manckoundia, P., … Giroud, M. (2010). Stroke in the Very Old: Incidence, Risk Factors, Clinical Outcomes
and
Access
to
Resources – A 22-Year Population-Based Study. Cerebrovascular Diseases, 29(2), 111–121. doi:10.1159/000262306
Voncken, F. L., Geurts, A. C., & Koopmans, R. T. (2010). Geriatric rehabilitation of stroke patients in nursing homes: a study
(2010). An Integrative Review of Factors Associated With Falls During Post-Stroke Journal
of
BMC
Geriatrics,
10(1),
15.
doi:10.1186/1471-2318-10-15 7. Frisoli, A., Procopio, C., Chisari, C., Creatini, I., Bonfiglio, L., Bergamasco, M., … Carboncini, M. C. (2012). Positive effects of robotic exoskeleton training of upper limb reaching movements after stroke. Journal
of
NeuroEngineering
and
Rehabilitation, 9(1), 36. doi:10.1186/1743-
3. Campbell, G. B., & Matthews, J. T.
Rehabilitation.
6. Eijk, M. S., Buijck, B. I., Zuidema, S. U.,
protocol.
2. Béjot, Y., Rouaud, O., Jacquin, A.,
Features,
D.
Health Administration. Generations, 34(2),
Reference
Aging
Cifu,
Nursing
Scholarship, 42(4), 395–404.
0003-9-36 8. Goodman, R. N., Rietschel, J. C., Roy, A., Jung, B. C., Diaz, J., Macko, R. F., & Forrester, L. W. (2014). Increased reward in ankle robotics training enhances motor
4. Carod-artal, F. J., Ferreira Coral, L.,
control and cortical efficiency in stroke.
Trizotto, D. S., & Menezes Moreira, C.
Journal of Rehabilitation Research and
(2009). Poststroke Depression: Prevalence
Development, 51(2), 213–27.
and
Determinants
in
Brazilian
Stroke
Patients. Cerebrovascular Diseases, 28(2), 157–65.
9. Grimaldi, G., & Manto, M. (2013). Functional impacts of exoskeleton-based rehabilitation in chronic stroke: multi-joint versus single-joint robotic training. Journal
of NeuroEngineering and Rehabilitation,
based study. Neurology India, 58(6), 863.
10(1), 113. doi:10.1186/1743-0003-10-113
doi:10.4103/0028-3886.73747
10. Jak, A. J., Urban, S., McCAULEY, A.,
14. Mikami, K., Jorge, R. E., Adams, H. P.,
Bangen, K. J., Delano-Wood, L., Corey-
Davis, P. H., Leira, E. C., Jang, M., &
Bloom, J., & Bondi, M. W. (2009). Profile
Robinson,
of hippocampal volumes and stroke risk
Antidepressants on the Course of Disability
varies by neuropsychological definition of
Following Stroke. The American Journal of
mild cognitive impairment. Journal of the
Geriatric Psychiatry, 19(12), 1007–15.
International Neuropsychological Society, 15(06),
890–897.
doi:10.1017/S1355617709090638
R.
G.
(2011).
Effect
of
15. Milot, M.-H., Spencer, S. J., Chan, V., Allington, J. P., Klein, J., Chou, C., … Reinkensmeyer, D. J. (2013). A crossover
11. Jung, J., Jang, I., Riener, R., & Park, H.
pilot
(2012). Walking intent detection algorithm
outcomes of two different types of robotic
for paraplegic patients using a robotic
movement
exoskeleton walking assistant with crutches.
survivors
International
BONES. Journal of NeuroEngineering and
Journal
of
Control,
study
evaluating training
using
the
in
the
functional
chronic arm
exoskeleton
Automation and Systems, 10(5), 954–962.
Rehabilitation,
doi:10.1007/s12555-012-0512-4
doi:10.1186/1743-0003-10-112
12. Koopman, B., Asseldonk, E. H. van, &
16. Nanda, S., Dey, T., Gulstrand, R. E.,
Kooij, H. van der. (2013). Selective control
Cudnik, D., & Haller, H. S. (2011). Fall
of gait subtasks in robotic gait training: foot
Risk Assessment in Geriatric-Psychiatric
clearance support in stroke survivors with a
Inpatients to Lower Events (FRAGILE).
powered
of
Journal of Gerontological Nursing, 37(2),
Rehabilitation,
22–30. doi:10.3928/00989134-20100730-01
exoskeleton.
NeuroEngineering
and
Journal
10(1), 3. doi:10.1186/1743-0003-10-3
10(1),
stroke
112.
17. Nilsson, A., Vreede, K. S., Häglund, V.,
13. Lee, J.-D., Weng, H.-H., Wu, C.-Y., &
Kawamoto, H., Sankai, Y., & Borg, J.
Wu, H.-M. (2010). Stroke risk factors and
(2014). Gait training early after stroke with a
subtypes in different age groups: A hospital-
new exoskeleton – the hybrid assistive limb: a study of safety and feasibility. Journal of
NeuroEngineering
and
Rehabilitation,
11(1), 92. doi:10.1186/1743-0003-11-92
Jönsson, A.-L., Murray, V., Wessari, T.,
18. Ommaya, A. K., Adams, K. M., Allman, R. M., Collins, E. G., Cooper, R. A., Dixon, C. E., … Wittenberg, G. F. (2013). Opportunities in rehabilitation research. Journal of Rehabilitation Research and Development, 50(6), vii–xxxii.
(2011).
Short-term
ankle
motor
performance with ankle robotics training in chronic hemiparetic stroke. Journal of Rehabilitation Research and Development, 48(4), 417–29. 20. Saleem, T., Khalid, U., & Qidwai, W. (2009). Geriatric patients’ expectations of their physicians: findings from a tertiary care hospital in Pakistan. BMC Health Services
Research,
9(1),
Holmqvist, L. W., & von Arbin, M. (2011). Rivermead Mobility Index Can Be Used to Predict Length of Stay for Elderly Persons, 5 Days After Stroke Onset. Journal of Geriatric Physical Therapy, 34(2), 64–71. 23. Veerbeek, J. M., van Wegen, E., van
19. Roy, A., Forrester, L. W., & Macko, R. F.
22. Sommerfeld, D. K., Johansson, H.,
Peppen, R., van der Wees, P. J., Hendriks, E., Rietberg, M., & Kwakkel, G. (2014). What Is the Evidence for Physical Therapy Poststroke? A Systematic Review and MetaAnalysis.
PLoS
ONE,
9(2),
e87987.
doi:10.1371/journal.pone.0087987 24. Vieira, E. R., Freund-Heritage, R., & Costa, B. R. da. (2011). Risk factors for geriatric patient falls in rehabilitation hospital settings: a systematic review. Clinical Rehabilitation, 25(9), 788–799. doi:10.1177/0269215511400639
205.
doi:10.1186/1472-6963-9-205 21. Sions, J. M., Tyrell, C. M., Knarr, B. A., Jancosko, A., & Binder-Macleod, S. A. (2012). Age- and Stroke-Related Skeletal Muscle Changes: A Review for the Geriatric Clinician. Journal of Geriatric Physical Therapy, 35(3), 155–61.
Table and figure
25. 3rd international congress on neurology and epidemiology. abu dhabi, UAE, november 21-23, 2013: Abstracts. (2013). Neuroepidemiology, 41(3-4), 223-316. doi:http://dx.doi.org/10.1159/000356326
Figure 1. Lower Limb exoskeleton
Figure 2. Pad of lower limb exoskeleton
Figure 3. Upper limb exoskeleton (a); multijoint training (b);singlejoint training (c)
Figure 4. Safety and feasibility test
Figure 5.
*) Jerk = Rate of change of acceleration ! indicates smoothness of a movement
\
Table 1. Algorithms Program Result on LL Robotics Exoskeleton with both non and disabled patient
Table 2. Assessment scores at pre-training (assest 1), after 8th week training (assest 3), and at 3 month follow up (assest 4)
Table 3. Motor behavior result between low reward and high reward group pre and post treatment
LITERATURE REVIEW Genistein in Tempeh as Potential Substance in Preventing Neovascularization in AgeRelated Macular Dengeneration Ayudhea Tannika1, Budiman Atmaja1, Giovanni Reynaldo1, Sri Handawati Wijaya1 1
Faculty of Medicin, Kristen Krida Wacana University (AMSA-Ukrida) Abstract
Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in persons over the age of 50. Indonesia has the highest prevalence of AMD compared with other countries in South-east Asia. Unfortunately, current AMD management methods offered requires a lot of funds. A side from that several problems were noticed during the clinical development of angiogenesis inhibitors. Recent studies have come up with the idea that the progression of AMD is associated with the angiogenic trait of retinal micro vascular. There are many researches that have been done on substances that may inhibit VEGF. These substances are known as Anti Vascular Endothelium Growth Factors (AVEGF). The objective of our paper is to suggest the prevention of AMD by using an AVEGF subtance genistein, which is also one of the compositions in tempeh. This study is conducted by several major steps such as searching the worldwide websites, journals and articles associated to AMD pathogenesis, what kind of substances take place in the progression of the disease, reviewing the potential substances in inhibiting the pathogenesis process, and reviewing tempeh with all the substances in it which has effects on certain process in AMD neovascularisation.The natural history of AMD is progressive destruction of the macula and thereby impairs central vision. In the retina, angiogenesis is an important component of normal physiological events and is also involved in pathological processes. It has been suggested that hypoxia is the primary stimulus for ocular neovascularization and hypoxia-induced angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Antiangiogenic drugs are used to reduce neovascularization in wet type AMD. Recent reports indicates that genistein, a naturally occurring isoflavonoid, exhibits strong antiangiogenic activity. Genistein significantly inhibits hypoxia-elicited bFGF and VEGF protein expression in a concentration-dependent manner.
Genistein suppresses the activation of bFGF receptor and adversely manipulate the expression of bFGF protein in RPE cells through autocrine way; this proves the hypothesis that genistein has an important application in the treatment of retinal and subretinal neovascularization. Keywords: Age-Related Macular Degeneration (AMD), neovascularization, genistein, tempeh
Introduction
with patientsâ&#x20AC;&#x2122; mobility and productivity, but
The improvement of Indonesian health care
also raises socio-economic effects in family,
system has increased the life expectancy in
relatives, and environment.
elderly. On the other side, the prevalence of degenerative
disease
in
Indonesia
Although AMD is not curable, in some cases
(atherosclerosis, diabetes mellitus, dementia,
severe vision loss can be controlled and
blindness and many more) has increased as
respond
1
to
laser
treatment
medications.
and
anti-
well. Visual impairment is one of the most
angiogenic
feared disabilities. Our ability to receive
several problems were noticed during the
information from the environment depends
clinical
on out ability to see. Loss of sight affects
inhibitors. In some patients, treatment with
activities of daily living and reduces the
an angiogenesis inhibitor results in an initial
quality of life furthermore. The major causes
response in the form of pericyte-poor leaky
of visual impairment are age-related; it
microvessels,
causes damage to the retina and optic nerve.
progression (acquired resistance). Secondly,
These causes include AMD, glaucoma, and
in contrast to initial expectations, signi!cant
diabetic retinopathy.2
clinical toxicities are observed during anti-
development
of
followed
Unfortunately, angiogenesis
by
tumor
angiogenic treatment.4 Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in
Recent studies have come up with the idea
persons over the age of 50 and it is second to
that the progression of AMD is associated
diabetes as the leading cause of blindness in
with the angiogenic trait of retinal micro
the 45 to 64 year-old age group.3 Indonesia
vascular. There are many researches that
has
AMD
have been done on substances that may
compared with other countries in South-east
inhibit VEGF. These substances are known
Asia. This fact is associated with the
as Anti Vascular Endothelium Growth
degenerative factors and with nutrition
Factors (AVEGF). The objective of our
problem. Blindness does not only interfere
paper is to suggest the prevention of AMD
the
highest
prevalence
of
by using an AVEGF subtance genistein,
people aged 50 years and older. It
which is also one of the compositions in
progressively destroys the macula and
tempeh. Genistein suppresses upregulation
thereby impairs central vision. AMD can be
of
factor
classified as either 'early stage AMD' or 'late
expression which can slow the progression
stage AMDâ&#x20AC;&#x2122;, depending on the stage of
of AMD.5,6
disease progression and characteristics of
vascular
endothelial
growth
the disease within the eye.7 In the early Methods
stages of AMD, typically pale spots
The objective of this study is to provide a
consisting of lipid and protein deposits from
platform for medical students to exchange
the retinal pigment epithelium (RPE), that
knowledge regarding AMD and to introduce
are termed drusen, accumulate as deposits
fellow medical students and people about
within Bruchâ&#x20AC;&#x2122;s membrane and beneath the
potential substance in Indonesian traditional
RPE. A second sign is the presence of subtle
food in slowing the progression of the
RPE changes (either increased or decreased
disease.
pigmentation or both). People with early stage AMD, which poses a future risk to
The method used for this paper is literature
vision, either have drusen at least 125
review. This study is conducted by several
microns in diameter present in the central
major steps such as searching the worldwide
retina, or have RPE abnormalities, or both
websites, journals and articles associated to
signs. (Figure 1)
AMD pathogenesis, reviewing what kind of
drusen that are smaller (i.e., 63 to <125
substances take place in the progression of
microns in diameter) is classified as very
the disease, looking for the potential
early AMD.1,3,7
The presence of only
substances in inhibiting the pathogenesis process, and reviewing tempeh with all the
Progressive changes in Bruch's membrane
substances in it which has effects on certain
and the RPE (e.g., fading drusen and
process in AMD neovascularisation.
pigmentary abnormalities) may lead to the development of abnormal blood vessels
Results
growing
Age-Related Macular Degeneration (AMD)
capillary bed, leading to neovascular AMD
is an eye disease that usually develops in
in
a
from
the
process
existing termed
choroidal choroidal
neovascularisation (CNV). In this process,
capacity for near visual tasks. This is
these new vessels leak or bleed into the
because the centre of the fovea usually or
underlying retinal layers, damaging the
eventually becomes affected by the loss of
retina, including the central macula region
retinal cells, thereby deteriorating central
leading to detachment of either the RPE or
vision and also because in many cases,
sensory retina by blood and fluid, and
geographic atrophy surrounds the central
subsequently leading to scarring (fibrosis)
macula before finally spreading to involve
and eventual atrophy, mostly with severe
it.9 (Figure 3)
vision loss or blindness. (Figure 1)1,7,8 Visual Impairment Neovascular AMD is characterized by the
Visual impairment can be broadly defined as
appearance of central visual blurring or
a limitation in one or more functions of the
distortion (metamorphopsia), with straight
eye or visual system, most commonly
lines appearing crooked or wavy with or
impairment of visual acuity (sharpness or
without
Color
clarity of vision), visual fields (the ability to
perception can also be affected. When
detect objects to either side, or above or
neovascular AMD occurs in only one eye,
below the direction of vision) and color
often no symptoms may be reported by the
vision.
blank
areas
(scotoma).
person due to compensation by the brain using the non!affected eye. (Figure 2) 1,8
In general, people with no AMD or with early stage AMD will continue to maintain normal vision and therefore the cost of
Geographic atrophy, the alternate form of
AMD to the person and society is relatively
late AMD, is characterized by light!sensitive
low. However, people with signs of early
cells in the macula slowly breaking down
stage AMD have a much greater risk of
(located directly above the RPE) and
developing late stage AMD. If and when this
becoming atrophic with complete loss of the
occurs, the impact of AMD on visual acuity
RPE and of adjacent choroidal elements
will become pronounced. Late stage AMD is
with marked choroidal thinning. Geographic
often first characterized by mild visual
atrophy may exist with relatively good
impairment for a short period but as the
distance vision but a substantially decreased
disease progresses within this stage, vision
loss may increase and can eventually lead to
undertaken. Some that believed to be the
blindness.6
predispose factors of AMD are genes associated with the complement cascade,
Risk and Protective Factors
Chromosome 10q locus, other major genetic
By eliminating or reducing modifiable risk
loci, gene-environment interactions, and
factors, (smoking, alcohol, high body mass
pharmacogenetic relationships.10
index suboptimal diet), the likelihood of
Several medical conditions have revealed
developing AMD may be reduced or its age
statistically significant associations with the
of onset delayed, along with the risk of
development of AMD. Three of these,
developing
obesity, hypertension, and high cholesterol
many
other
debilitating
conditions that share these risk factors, such
levels,
are
as cardiovascular disease. The potential role
cardiovascular
of diet and vitamin supplements stems from
disease itself (and prior history of stroke)
the hypothesis that oxidative stress is one
has been identified as a contributor to the
pathogenesis mechanism by which AMD
development of AMD, although findings
develops, and that diet high in antioxidant
have not been entirely consistent. Medical
micronutrients can protect against this
conditions that contribute in developing
oxidative stress.9
AMD
are
hypertension,
also
risk
disease.
overweight high
factors
for
Cardiovascular
and
cholesterol
obesity, level,
AMD also results from the interaction of
cardiovascular disease, and chronic kidney
genetic predisposition and environmental
disease.10
factors. The relationship between the risk of developing AMD and genetics is well
Ocular Factor has been suspected as one of
established from family and twin studies.
the potential factor that will increase the
For example, heritability of up to 70% has
incidences.
been
2007;
behind this association has been that shorter
Fajnkuchen and Cohen 2008). These are
hyperopic eyes have higher scleral rigidity
further
general,
which impairs the choroidal circulation. The
although some significant relationships have
influence of iris color on AMD has been
been found, there are inconsistencies in
widely investigated. In The Beaver Dam
findings and further research needs to be
Eye Study (BDES), no relationship was
estimated discussed
(Scholl below.
et
al In
The
postulated
mechanism
found between iris pigmentation and the
to halt the growth of blood vessels into the
incidence and progression and incidence and
central retina, is effective in a small
progression of AMD at five years. However,
proportion of patients with wet AMD.
at the 10!year follow!up, people with brown
Clinicians observe that abnormal blood
eyes were significantly more likely to
vessel growth reoccurs after either laser or
develop soft indistinct drusen compared to
PDT. Clearly additional therapeutic options
people with blue eyes, and were less likely
are needed to address this problem and to
to develop increased retinal pigment and
restore the lost function. Considering the
10
known effects of oxidative stress on RPE
RPE depigmentation.
cell health and function, an obvious AMD current management
therapeutic approach for the maintenance of
The management of AMD aims to minimize
RPE
visual loss and disability in order to
supplementation with antioxidants.12
cell
function
is
nutritional
maintain independence, rather than actually treating the pathology of the disease.11
Antiangiogenic
Current therapies either target RPE or CNV.
neovascularization
The wet, form of macular degeneration
degeneration. A substance in the body called
affects 15% of those diagnosed with AMD,
VEGF is responsible for the growth of new
but accounts for ~80% of the visual
blood vessels. There are some drugs can be
complications leading to blindness.12 There
used for wet AMD: Macugen (pegaptanib
are some medications that can be use: laser
sodium), Lucentis (ranibizumab), EGF Trap-
coagulation therapy, photodynamic therapy
Eye
(PDT), transpupillary thermotherapy (TTT),
Endostatin, Pazopanib. Based on a study that
antiangiogenic
tested some antiangiogenic drugs represent
drugs
,
radiation,
and
surgery.11,12
(Eylea),
drugs
are
stopping
in
wet
macular
Avastin
(bevacizumab),
the mechanism and side effect of the drugs.12
Conventional
laser-photocoagulation
surgery to remove CNV is indicated in only
Macugen is a VEGF antagonist. The side
10 - 20% of patients with wet AMD. After
effects of macugen are: ocular discomfort,
laser surgery, patients report diminished
eye pain, reduced visual acuity, visual
visual acuity. Likewise, PDT, which is used
disturbance, corneal edema, blurred vision
and
dizziness.11,13
Ranibizumab
a
retinopathy, glaucoma or refractive error.
monoclonal antibody fragment (Fab) derived
Other direct cost includes nursing home care
from the same parent mouse antibody as
due to visual impairment, government
bevacizumab (Avastin). Ranibizumab binds
programs for people who are visual impaired
to and inhibits a number of subtypes of
and guide dogs. Lost productivity is defined
vascular
A
as the cost of lower labor force participation
(VEGF-A). The most common side effects
and lower wages among people who are
in
conjunctiva
visually impaired or blind compared to those
hemorrhage, eye pain, vitreous floaters,
in the same age group who have normal
increased
vision.14
endothelial
clinical
trials intraocular
growth were
is
factor
pressure,
and
intraocular inflammation. VEGF trap-eye works by blocking VEGF activities has
The Annual excess monetary impact to
become a mainstay therapy for treating eye
individuals with visual impairment and
diseases that have angiogenesis at their
blindness, caregivers and other healthcare
etiological core.
11
payers is calculated at $5,48 billion (medical care expenditures spend $5,12 billion and
Monetary difficulties that can arise from
informal care costs spend $0,36 billion). On
the disease
top of the $5,48 billion is an annual health
AMD can cause huge financial loss which
utility loss of approximately $10,5 billion.
can impact the patient and the government.
Medical care expenditures reflect costs
This financial loss is divided into direct
associated with events such as outpatient
medical costs, other direct costs, and lost
doctor
productivity cost. Estimated annual financial
hospital stay, dental visits, home care and
burden to U.S. economy due to adult vision
also medical supplies and prescription drugs.
problem such as AMD, cataract, diabetic
Informal care costs refer to the value of time
retinopathy, and glaucoma is $35,4 billion.14
related to unpaid care provided by friends
visits,
emergency
room
visits,
and family members. Health utility is a Direct medical cost refer to outpatient
useful measure for evaluating quality of life
services, inpatient services, prescription
in chronic medical conditions where there is
drugs, vitamins and other medications used
little or no impact on mortality in the short
by people with AMD, cataract, diabetic
term. It enables health-related quality of life
(e.g., distress, depression, mobility, social
confusion with the referral process; and
limitations) to be quantified and transformed
problems
into quality-adjusted life years (QALYs)
rehabilitation services.8
using
transport
to
access
gained or lost. QALYs are used in costeffectiveness analyses. For the 3,7 million
Based on the informations regarding the side
people who are visually impaired or blind,
effects of current anti-angiogenic agents,
the loss in QALYs is calculated at over
monetary difficulties in treating the disease,
209,200. In the U.S., a regularly used value
and barriers to rehabilitation access for
14
for QALYs is $50,000.
AMD patients, we suggest involving a management with natural food resource. In
The following data above is just the
this case, tempeh is used as the suggested
description of huge financial excess in adult
angiogenic inhibitor because it consists of
vision problem, including AMD. This data
genistein, a substance which is able to
can be the prediction for Indonesia, although
inhibit neovascularization in late AMD
the prevalence is less than the U.S.
14
pathogenesis.
Rehabilitation services difficulties
Tempeh is a fermented soybean product that
It has been estimated that 90% of people
undergoes a sequence of soaking, cooking,
with vision impairment have useful residual
inoculation,
vision that could benefit from rehabilitation
originated in the Java regions of Indonesia.
services. The barriers to access low vision
Tempeh is a popular food among all socio-
rehabilitation are: lack of awareness of
economic groups throughout the country of
services offered among those with visual
Indonesia. One serving of tempeh (83 grams
impairment and referring professionals;
= " cup) contains 15,7 grams of protein.
some people did not recognize or accept that
(Figure 5)15,16
and
fermentation.
Tempeh
they had vision loss that would warrant specialized services; misconceptions that
Discussion
rehabilitation services are only for those
In the retina, angiogenesis is an important
with severe vision loss, which is heightened
component of normal physiological events
by
and
rehabilitation
service
organizations
directing publicity to people who are blind;
is
also
involved
in
pathological
processes. It has been suggested that
hypoxia is the primary stimulus for ocular
activated.
neovascularization and hypoxia induced
cellular
angiogenic factors such as basic fibroblast
expression of the fibroblast growth factor
growth factor (bFGF), vascular endothelial
receptor have been suggested to play a role
growth factor, epidermal growth factor,
in
transforming growth factor beta, could play
proliferation by short-term hypoxia, such as
an important role in the development of
that resulting from retinal blood vessel
choroidal and retinal neovascularization.10
occlusion. Endothelial response can run the
Recent reports indicated that genistein, a
gamut from increased cell proliferation and
naturally occurring isoflavonoid exhibits
synthesis of IL-10, and upregulation of
strong antiangiogenic activity. Recently, it
TGFB to increases in glucose transporter,
has been reported that genistein could inhibit
intracellular
ocular neovascularization in vivo.6,10 The
membrane-associated proteins, enthelin-1,
study conducted by Shan, et.al. was
and platelet aggregating factor. The origin of
undertaken to investigate the possible
the endothelial cells can affect the manner in
mechanism of inhibition of genistein on
which they respond to hypoxia. In this
choroidal and retinal neovascularization by
regard, hypoxia-induced phosphotyrosine
observing the time course changes of bFGF
has been shown to be markedly blocked by
protein expression induced by hypoxia and
the
the effects of genistein on hypoxia induced
herbimycin-A
bFGF protein expression in human retinal
dihydroxycinnamate, but not by the protein
pigment epithelial (RPE) cells.10
tyrosine kinase inhibitor genistein.6,10
Tyrosine-phosphorylated proteins, vascular
In other words, VEGF, bFGF, and tyrosine
endothelial
kinase
growth
factor,
and
basic
the
Tyrosine proteins
and
activation
protein
phosphorylation
of
calcium,
tyrosine
feature
and
changes
in
endothelial
of the
cell
prostaglandins,
kinase
inhibitors
methyl
prominently
in
2,5-
retinal
fibroblast growth factor increase after
neovascularization diseases. Each of them
occlusion
vessel,
augment proliferation of endothelial cell,
especially within the occluded blood vessel.
especially under hypoxia.15 Targeting of
In addition, two signal proteins in tyrosine
angiogenesis is a major therapeutic avenue.
kinase pathways, namely phospholipase C#
A large variety of new agents are under
and mitogen-activated protein kinase, are
development in order to inhibit the process
of
a
retinal
blood
of
neovascularization
Unfortunately,
in
current
AMD. therapeutic
glycosides in soybeans and most soy foods consumed
in
the
Western
countries.
management on inhibiting angiogenesis
Glycoside ISF cannot be absorbed unless
process
hydrolyzed and converted to the bioactive
of
AMD
still
has
several
disadvantages for the patients: high-cost
forms,
genistein
and
daidzein,
both
treatment, invasive (some therapeutic agent
aglycones, by intestinal microflora or in
has to be injected in vitreous humor), and
vitro fermentation. Most traditional Asian
causing unwanted side effects.10
soy foods contain high levels of aglycone ISF that are more bioavailable and active
Due to the increased incidence of the
than the glycoside ISF.16
unwanted side effects from the antiangiogenesis drugs, AMD patients started to
ISF are structurally similar to mammalian
seek other options which are able to slow the
estradiol
disease process. During the last 10 years,
and " isoforms of estrogen receptor (ER).
much research has been conducted on the
However, their binding affinity to ER" is
potential benefits of soy-based foods in
"20 times higher than that to ER!, and their
preventing chronic diseases such as cancer
efficacies of activating the binding of
and osteoporosis. These studies often focus
ER" to estrogen response elements (ERE) of
on specific substances called isoflavones,
target genes are 500â&#x20AC;&#x201C;850 times higher than
which are found in relatively high amounts
that of activating the binding of ER! to
in soybeans. Isoflavone
5
and
can
bind
to
both !
ERE. (ISF)
are
major
soy
ER! and ER" share little or no homology
phytoestrogens present in soy foods and
between their ligand-binding and N-terminal
require washing in alcohol for removal. Soy
transactivation domains. This feature may
foods and soy-based infant formulas are rich
contribute to their opposite effects on
sources of ISF and contain "1â&#x20AC;&#x201C;4.2 mg
regulating
ISF/g, whereas soy ISF supplements contain
physiological
up to 500 mg ISF/g. Genistin, daidzin, and
estrogenic
glycitein are the main soy ISF. Both genistin
proliferation of human breast cancer cells
and daidzin are conjugated to sugars as
through
gene
expression
functions.
For
compounds binding
to
ER! but
and
example, stimulate suppress
proliferation
via
ER" .
Therefore,
the
selective receptor binding may confer on
used ARPE-19 as retinal pigment epithelial cells culture. (Figure 7, Figure 8) 10,18
ISF the ability to regulate physiological functions in a different way from estrogen.16
The result of the study was the increase of
(Figure 6)
bFGF protein expression due to worsen hypoxia; and the genistein significantly
Recent findings suggest the maximum
inhibited hypoxia-elicited bFGF protein
health benefits of genistein are evident when
expression in a concentration-dependent
it is made available in its nonglucoside form.
manner.
A review of the literature shows that a high level of genistein is present in tempeh.
Conclusions 1. Age-related
Genistein
has
fungistatic, and
been
found
antioxidative,
diuretic
Degeneration
have
(AMD) is the leading cause of severe
antimutagenic,
vision loss in persons over age 50 and it
vitro
is second only to diabetes as the leading
antioxidative properties of isoflavones are
cause of blindness in the 45 to 64 year-
influenced by the number of hydroxyl
old age group. Indonesia has the highest
groups present on the molecules; the
prevalence of AMD compared with
addition of a glucose molecule to the
other countries in South-east Asia.
aglycone
properties.
decreased
The
to
Macular
the
property of those isoflavones.
in
antioxidative 18
2. Main process in AMD pathogenesis is the neovascularization in retinal layer, which
involves
some
chemical
In a study conducted by Jie Shan-Jun, et.al
substances like VEGF, bFGF, and
in 2004, the writer investigated the possible
tyrosin kinase. The more active the
mechanism of inhibition of genistein on
process, the worse the results will
choroidal and retinal neovascularization by
become.
observing the time course changes of bFGF
3. Several problems have been noticed
protein expression induced by hypoxia and
during the clinical development of
the effects of genistein on hypoxia-induced
angiogenesis
bFGF protein expression in human retinal
preclinical
pigment epithelial (RPE) cells. The author
resistance to angiogenesis inhibitors
inhibitors. and
clinical
In
both settings,
occurs. In some patients, treatment with
2. Zhang, K., Zhang, L., Weinreb, R.
an angiogenesis inhibitor results in an
N.
initial response, followed by tumor
discovery:
progression (acquired resistance). In
mechanisms for retinal diseases and
other patients, intrinsic resistance is
glaucoma. Nature Reviews, 11, 541.
being observed. In contrast to initial expectations,
signi!cant
clinical
(2012).
novel
angiogenic treatment.
Optometric
serves
as
tyrosine
kinase
receptor
targets
and
(2010). Care of the patient with agerelated
kinase (TK) inhibitor and bFGF receptor
drug
3. American Optometric Association.
toxicities are observed during anti4. Genistein in tempeh serves as tyrosine-
Ophtalmic
macular
degeneration.
Clinical
Practice
Guideline, 8. 4. Gotink, K. J., Verheul, H. M. W. (2010).
Anti-angiogenic
tyrosine
(RTK), so it might be safe to conclude
kinase inhibitors: what is their
that genistein suppressed the activation
mechanism of action? Angiogenesis,
of
13, 2, 6-7. doi: 10.1007/s10456-009-
bFGF
receptor
and
adversely
manipulate the expression of bFGF
9160-6
protein in RPE cells through autocrine
5. Garlock, L. A. (2000). The effect of
way; prove the hypothesis that genistein
various acidic solutions on the
have an important application in the
concentration of genistein in tempeh,
treatment of retinal and subretinal
5,18-9.
neovascularization.
6. Nakajima, N., et. al. (2005). Analysis of isoflavone content in tempeh, a
References
fermented soybean, and preparation
1. Erry. (2012). ARMD (Age-related macular
degeneration).
Penelitian
dan
Sistem
Kebijakan
Badan
&
Pusat
Pengembangan
Penelitian
Kesehatan, dan
of
a
new
isoflavone-enriched
tempeh. Journal of Bioscience and Bioengineering, 100, 685. 7. Cook, H. L., Patel, P. J., Tufail, A. (2008).
Age-related
Kesehatan,
degeneration:
Departemen Kesehatan RI: CDK, 39,
management.
431,4-5.
Bulletin, 85, 128,134.
Pengembangan
diagnosis British
macular and Medical
8. Macular Degeneration Foundation.
14. Prevent Blindness America. (2007).
(2011). Eyes on the future: a clear
The economic impact of vision
outlook
problems, 4-6.
on
age-related
macular
degeneration.
Deloitte
Access
Economics, 21-24.
15. Kumar,
A.
S.,
Kavimani,
S.,
Jayaveera, K. N. Current research
9. Paul, M., Julie, H., Robert, C.
and
clinical
management
of
(2011). Eyes in the future: a clear
angiogenesis. International Journal
outlook
on
age-related
macular
of Experimental Pharmacology, 2, 2-
report.
Macular
4.
degeneration
Degeneration Foundation, 20-7, 5275.
16. Chao, W. X. (2008). Health effects on soy protein and isoflavones in
10. Shan, J. J., Yuan, Z. L., Wang, B.
humans. The Journal of Nutrition,
(2004). Effect of genistein on basic
138, 2.
fibroblast growth factor expression
17. Kiriakidis,
induced by hypoxia in ARPE-19
tempeh
cells.
isoflavones
International
Journal
of
Ophtalmology, 4, 1-3.
et.al.
(fermented
angiogenesis
11. Porte, C. (2012). Pathogenesis and
(2004).
chorioallantoic
inhibit in
Novel
soyabean) in
the
membrane
vivo chicken assay.
management of age-related macular
British Journal of Nutririon, 93, 318.
degeneration. Scottish Universities
18. Haron, H., et.al. (2009). Daidzein
Medical Journal, 1, 11-12. 12. Sharma, Anand,
N.
K.,
Prabhakar,
A.
(2009).
and genistein contents in tempeh and S.,
selected soy products. Journal of
Age-related
Agricultural and Food Chemistry,
macular degeneration â&#x20AC;&#x201C; advances and trends. Annuals of Neurosciences, 16, 3-5. 13. Kamajian, A. T. (2011). In the pipeline: 10 approaches that may puh back amd, 40-42.
115, 1353-5. 19. De Juan, E. (1999). Use of protein tyrosine kinase pathway inhibitor in the treatment of retinal ischemia or ocular inflammation, 1-2.
Tables and figures
Figure 1 An eye with advanced geographic atrophy (dry AMD) in fundus photograph7
Figure 2 An eye with neovascular age-related macular degeneration in fundus photograph7
Figure 3 Classification of age-related macular degeneration7
Figure 4 Appearance in AMD patients1
Figure 5 Daidzein (white bar) and genistein (black bar) content in selected soy products16
Figure 6 Chemical structures of genistein in soy foods17
Figure 7 bFGF protein expression after hypoxia in ARPE-19 cells10
Figure 8 Effect of genistein on bFGF protein expression after hypoxia in ARPE-19 cells10
LITERATURE REVIEW Correlation between Parkinson’s Disease and Depression in Elderly Patients Andrey Setiawan1, Andreas Billy Dharmala1, Elisabeth Martha1, Eifraimdio Paisthalozie1 1
Faculty of Medicine, Kristen Krida Wacana University (AMSA-Ukrida) Abstract
Parkinson’s disease (PD) is one of the neurodegenerative condition which tends to affect patient in his/her late days. Parkinson’s disease mostly present with motoric and non-motoric abnormalities. Depression is a phase of condition more than just sadness or a low-mood, but it is considered as a serious illness that can cause severe effects on both physical and mental health. Symptoms of classic depression and depression which happened in PD’s patient are sometimes very hard to be differed, and it is important to analyze each of the depressive symptoms to obtain information whether the patient may have depression before he/she suffer from Parkinson or he/she experienced those depressive symptoms after the Parkinson’s worsen the patient’s life. To know the scientific fact about the exact correlation between Parkinson’s disease and depression. We are gathering information related to the topics we want to discuss, in journals and textbook, analyzing it and combining all of the information contained in the journals. There are several hypotheses to explain the relation between depression and Parkinson’s disease. The link between Parkinson’s disease and depression is complex. Effectively caring for the patient with Parkinson’s disease requires careful monitoring of drug treatment, emphasis on teaching selfreliance, and generous psychological support. Keywords : Parkinson’s, neurodegenerative, depression
Introduction
affected millions of humans. It is considered
Parkinson’s disease (PD) is one of the
as a common neurodegenerative disease
neurodegenerative condition which tends to
with a lifetime incidence of 2.5% and a
affect patient in his/her late days. Patient
prevalence of at least 2% in individuals over
with Parkinson’s disease mostly present
70 years of age. This disease afflicts
with motoric and non-motoric abnormalities,
primarily the dopaminergic neurons, which
although motoric function impairment tend
have their cell bodies located in the
to be more disrupted than non-motoric
substantia nigra pars compacta. The loss of
abnormalities but there’s always a small
these cells progressively will lead to a
chance that someone having Parkinson in an
decrease in striatal dopamine levels, which
atypical form, which may be challenging for
in turn will affect the decrease in striatal
the clinicians to make the early diagnosis.
output to the thalamus and the result is
As we all have known before, the main
motoric function abnormalities, such as
clinical manifestation of Parkinson’s has
bradykinesia and rigidity. Basal ganglia
been grouped into a common term, which is
plays an important role in producing rigidity
called T.R.A.P. The term itself is an
in PD’s patient.
abbreviation of Tremor at rest, Rigidity,
greatly disrupt many daily tasks ad activities
Akinesia (or Bradykinesia), and Postural
such as walking, talking, writing, eating, and
Instability. In addition, flexed posture and
etc., which may cause the patient to be more
freezing (motor blocks) have been included
dependable to their caregivers.
Symptoms of PD often
among classic features of Parkinsonism, with PD as the most common form. A wide
Depression is a phase of condition more
range of ‘non-motor’ symptoms are also
than just sadness or a low-mood, but it is
common in patient with PD, such as
considered as a serious illness that can cause
sleeping’s problems, fatigue, pain, slowness
severe effects on both physical and mental
of thinking, memory problems, constipation
health. People living life along with
and urinary incontinence. Other than that,
depression have a trouble in functioning
various degrees of cognitive, autonomic and
normally in his/her daily life, oftentimes
psychiatric abnormalities may also be
patients are unable to find pleasures in any
present, besides having the cardinal features
of their activities. Common behaviors,
of Parkinson’s disease. Worldwide, PD has
feelings and thoughts include sadness,
moodiness,
increased
irritability
and
frustration, feeling worthless, slowing down
symptoms of Parkinson and the depression itself.
of thoughts or actions and withdrawing from close family and friends as the result of great
Methods
disappointment toward people around the
We are gathering information related to the
patient.
Patients with PD are at risk for
topics we want to discuss, in journals and
having
depression
co-morbid
textbook, analyzing it and combining all of
condition. Prolonged depression in PD’s
the information contained in the journals to
patient may alter patient’s mental status as
show the correlation of Parkinson’s disease
time goes by, if it is left untreated or
and depression. Shortly, we are studying
detected
scientific literature to reach our objectives,
later.
as
the
Symptoms
of
classic
depression and depression which happened
as we have mentioned above.
in PD’s patient are sometimes very hard to be differed, and it is important to analyze
Results
each of the depressive symptoms to obtain
Several
information whether the patient may have
pathophysiological
depression
higher prevalence of depression in PD
before
he/she
suffer
from
hypotheses
none
of
try
to
provide
explanation which
for
have
a the
Parkinson or he/she experienced those
patients,
been
depressive symptoms after the Parkinson’s
empirically tested. The most well-known are
worsen the patient’s life.
the “serotonergic” and the “dopaminergic” hypotheses. The serotonergic hypothesis
The main objective of this paper is to obtain
was formulated by Mayeux et al in 1984 and
scientific fact about the exact correlation
is based on the finding that serotonergic
between Parkinson’s disease and depression,
activity in the cerebrospinal fluid and the
not only based on the correlation from
brains of PD patients is lowered. As
pathological view but also how patient with
serotonin has the ability to inhibit striatal
PD could generate depression in his/her life.
dopamine release, reduction of serotonergic
The side objectives of this paper are to
activity is seen as a functional mechanism
determine the best management which
compensating for the reduced availability in
proven have a benefit to minimize the
the striatum. At the same time, it is known that a reduced serotonergic tone is a risk
factor for depression. This may explain the
psychomotor
higher prevalence of depression in PD and
noradrenergic activity with anhedonia, and
the fact that depression may occur even
reduced
before the diagnosis. It also explains the
depressive
exacerbation of extrapyramidal symptoms
insomnia. For several reasons, this approach
that may occur during treatment with a
is probably too simplistic. It may be
selective
assumed that not the regional absolute
serotonin
reuptake
inhibitor
(SSRI). (Leentjens A.F.G., 2004)
serotonergic
dopaminergic
reduced
activity
symptoms,
with
anxiety,
and
activity of one neurotransmitter but the balance
The
retardation,
different
neurotransmitter
also
activities is responsible for the production of
described in 1984, considers degeneration of
symptoms. The hypothesis also fails to
the mesolimbic and mesocortical structures
explain why some patients do have and
of the dopaminergic system as the cause of
others do not have depressive complaints in
depression.
spite
These
hypothesis,
of
pathways
play
an
important role in the so-called self-reward
of
similar
pathophysiological
abnormalities. (Leentjens A.F.G., 2004)
systems. Compromising these structures would increase the risk of depression. This
Furthermore,
hypothesis
higher
personality, and coping strategies also play a
prevalence of depression in PD and the
role in the complex interaction of biological
mood-elevating effects of some of the
and
dopamine
“vulnerability model” is thus a more
also
explains
agonists.
the
(Leentjens
A.F.G.,
2004)
psychosocial
psychological
appealing
factors,
factors.
hypothesis
to
The explain
interindividual differences. In the past few Other
researchers
have
followed
an
years,
the
influence of
deep
brain
the
subthalamic
approach along the lines of “functional
stimulation
psychopathology” and hypothesized a more
nucleus (STN) on mood has shed a new light
direct link between depressive symptoms
on depressive symptoms in PD, but also on
and altered neurotransmitter activities, rather
mood regulation in general. It has been
than propose a higher vulnerability. In both
demonstrated that STN DBS may lead to
depression and PD, lowered dopaminergic
improved mood, sometimes progressing to
activity in the frontal lobe is associated with
(DBS)
of
pathological laughter or mania. (Leentjens
about the future. In most cases, the co-
A.F.G., 2004)
existence of the conditions is thought to be a combination of biological changes in the
Unintentional stimulation of the substantia
brain
caused
by
Parkinson’s
disease,
nigra, or deeper subthalamic structures,may
together with trying to adjust to major life
produce acute depression, with delusions
changes. (Beyondblue, 2011)
and even suicidality. These findings imply a role for the basal ganglia in mood regulation
Discussion
that has to be explored. It will be a challenge
Named for James Parkinson, the English
to extend existing neuroanatomic hypotheses
physician who wrote the first accurate
of the pathophysiology of depression, such
description
as the model of dysfunctional limbiccortical
Parkinson’s disease (also known as shaking
pathways proposed by Mayberg, with this
palsy)
newly discovered role of the basal ganglia.
progressive muscle rigidity, akinesia and
(Leentjens A.F.G., 2004)
involuntary
of
the
disease
characteristically tremor.
in
1817,
produces
Deterioration
is
a
progressive process. Death may result from The link between Parkinson’s disease and
complications, such as aspiration pneumonia
depression is complex. Unlike several
or some other infection.
hypotheses mentioned before explaining about how can we see PD and depression on their pathophysiology point-of-view, there are more to explore as those hypothesis cannot answer all questions asked. One of them is being diagnosed with Parkinson’s disease can also trigger depression and anxiety. Adapting to the disease involves many adjustments to a person’s life and can dramatically
affect
how
the
person
functions. Changes to a person’s social life, work pattern and financial situation may cause stress and sadness, along with worry
Parkinson’s pathophysiology Parkinson’s
disease
is
a
degenerative
process which involving the dopaminergic neurons in substantia nigra (the area of the basal ganglia that produces and stores the neurotransmitter dopamine). This area plays an important role in the extrapyramidal system,
which
controls
posture
and
coordination of voluntary motor movements. Normally, stimulation of the basal ganglia results in refined motor movement because acetylcholine (excitatory) and dopamine (inhibitory)
release
are
balanced.
Degeneration of the dopaminergic neurons
as a state of profound sadness. It is also
and loss of available dopamine leads to an
variously known as melancholia, ‘the blues’
excess of excitatory acetylcholine at the
or living with/having ‘the black dog’.
synapse and consequent rigidity, tremors,
Depression can develop across the lifespan –
and bradykinesia. Other non-dopaminergic
from childhood to old age. The degree or
neurons
possibly
intensity of the condition also varies greatly
contributing to depression and the other non-
from person to person, manifesting as a
motor disease.
may
be
affected,
symptoms
associated
Also,
the
basal
to
the
interconnected potentially
affecting
with
this
mild, moderate, or severe (major) disorder.
ganglia
are
Depression is now considered one of the
hypothalamus,
most important causes of non-fatal disease
and
burden worldwide, a burden considered to
endocrine function as well. Current research
be greater than that of having arthritis,
on the pathogenesis of Parkinson’s disease
asthma, diabetes or angina. In part, the
focuses on damage to the substantia nigra
greater burden is believed to be accounted
from oxidative stress. Oxidative stress is
for by relatively poorer clinical management
believed to diminish brain iron content,
compared to these other conditions. Indeed,
impair
inhibit
it is highly likely that people with these
antioxidant and protective systems, reduce
other chronic diseases will have comorbid
glutathione secretion and damage lipids,
depression.
mitochondrial
autonomic
function,
proteins, and deoxyribonucleic acid. Brain cells are less capable of repairing oxidative
A long held view on the pathophysiology of
damage than any other tissues. (McCann
depression is that there is a chemical
J.A.S., Moreau D., Robinson J.M.,2011)
imbalance in the brain associated with decreases in the synaptic levels of the
Depression’s pathophysiology
biogenic amine neurotransmitters, serotonin
On the other hand, depression is one kind of
(or
affective disorders, the other end is mania.
noradrenaline
Some people experience only one of these
controlling mood. This is referred to as the
states, while others cycle from one state to
biogenic
the other. The later condition is referred to
Serotonin is considered to be more closely
bipolar disorder. Depression is characterized
associated with the control of mood than
5-hydroxytryptamine, (NA)
amine
in
theory
5-HT) the of
and
pathways depression.
noradrenaline. However, noradrenaline is
certain neuronal growth factors, such as
more strongly implicated in motor activity,
brain-derived neurotrophic factor (BDNF),
which also changes in this condition.
may
Another
depression,
biogenic
amine
transmitter,
be
deficient. the
In
chronic
hypothalamic
severe hormone
dopamine (DA) may also be involved in the
corticotropin-releasing factor is elevated,
pathophysiology, but its specific role in the
which in turn induces cortisol secretion from
dysfunction remains relatively less clear. In
the adrenal gland. Changes in the levels of
support of this view, antidepressant drug
these hormones correlate with a decrease in
treatment that raise the synaptic levels of
the size of the hippocampus, which is
serotonin and/or noradrenaline in the brain
involved in the formation of long-term
can induce clinical improvement in patients
memories and contributes to the control of
with
emotion. (Hales M., Bullock S., 2013)
depressive
illness.
This
theory,
however does not reflect the full picture of the pathophysiological processes underlying
How to deal with Parkinsonâ&#x20AC;&#x2122;s disease
depression. Acute elevations of synaptic
There is no cure for PD and no medication
transmitter levels are not sufficient to
that slows or stops the progression for now.
improve mood, as it takes two to six weeks
Therefore the treatment is aimed to suppress
of therapy before clinical benefits are
or reduce the symptoms of the least amount
observed.
of adverse effects from the drugs. It includes
Therefore,
long-term
antidepressant drug treatment is required for
non-pharmacologic,
pharmacologic,
and
the relief of depression. Further to this,
when indicated, surgical methods. Non-
drugs that antagonize central serotonin
pharmacologic interventions offer group
receptors do not induce depression. This has
support, education, daily exercise, and
led to a change in the pathophysiological
adequate nutrition. (Porth, C.M., Gaspard,
perspective in more recent years. It is now
K.J., Noble K.A., 2007)
argued that the way the brain is wired changes in depressive illness. There is
Pharmacologic
treatment
evidence that connections between neurons,
determined by the severity of symptoms.
connections between each brain region and
Anti-Parkinson drugs act by increasing the
the size of brain regions change in
functional
depression. In depression, the availability of
dopaminergic system, or by reducing the
ability
of
the
usually
is
underactive
excessive influence of excitatory cholinergic neurons. Drugs that improve the function of
Bromocriptine, pramipexole, and ropinirole
the dopaminergic system include those that
are dopamine agonists that act directly to
increase
(levodopa),
stimulate dopamine receptors. These are
stimulate dopamine receptors (dopamine
synthetic compounds that mimic the action
receptor agonists), or retard the breakdown
of dopamine at the dopamine receptor (the
of
oxidase
message receiver) in the striatum. These
inhibitors). Dopamine does not cross the
agents are not as powerful as levodopa and
blood-brain barrier. Levodopa does cross the
are usually used in addition to levodopa for
blood-brain barrier, but only in small
patients who experience end-of-dose failure
amounts due to its high metabolism outside
using
the brain. However, when levodopa (a
dopamine agonist that is supplied in a
decarboxylase
in
transdermal system. The dopamine agonists
combination with carbidopa, the peripheral
can be used as initial or adjunctive therapy
metabolism of levodopa is reduced, plasma
in Parkinson disease and can be given in
levels of levodopa are increased and its half-
combination
life is longer, more levodopa is available for
(Porth, C.M., et.al., 2007;Golbe, L.I., Mark,
entry into the brain, and a smaller dose is
M.H., Sage, J.I., 2010)
dopamine
dopamine
levels
(monoamine
inhibitor)
is
given
levodopa
alone. Rotigotine
with
is
a
carbidopa/levodopa.
needed. A later adverse effect of levodopa treatment
is
the
so-called
on–off
Apomorphine is another dopamine agonist
phenomenon, in which frequent, abrupt, and
that can be given intravenously. Rotigotine
unpredictable
motor
is only approved by the U.S. Food and Drug
performance occur during the day. These
Administration (FDA) for initial treatment
fluctuations include “on” periods without
of Parkinson disease, whereas apomorphine
dyskinesia, “on” periods with dyskinesia,
is used as a rescue medication in patients
and periods of bradykinesia (the “off”
experiencing
response). Some fluctuations reflect the
delayed
timing of drug administration, in which case
thought to augment release of dopamine
the “on” response coincides with peak drug
from the remaining intact dopaminergic
levels and the “off” response with low drug
terminals in the nigrostriatal pathway of
levels. (Porth, C.M., et.al., 2007)
persons with Parkinson disease. It has
fluctuations
in
“on”
sudden
“off”
periods.
periods
or
Amantadine
is
anticholinergic activity, may help release
and
dopamine, and may even have an effect on
2007)
hallucinations. (Porth,
C.M.,
et.al.,
excitatory neurotransmitters in the basal ganglia. It is used to treat persons with mild
All the major surgical procedures performed
symptoms but no disability. Selegiline and
to relieve symptoms of PD are done
rasagiline are monoamine oxidase type B
stereotactically. This means that the target
inhibitors
metabolic
cells in the brain, which have been selected
breakdown of dopamine. Selegiline and
either for destruction or stimulation, are
rasagiline may be used as adjunctive
reached with the aid of a computerized
treatment to reduce mild onâ&#x20AC;&#x201C;off fluctuations
guidance system through a small hole in the
in the responsiveness of persons who are
skull.
receiving levodopa. (Porth, C.M., et.al.,
appropriately-chosen target and the cells in
2007; Golbe, L.I.,et.al., 2010)
the targeted nucleus (group of cells) are then
that
inhibit
the
A
needle
is
guided
to
the
either destroyed or stimulated electrically. Because dopamine transmission is disrupted
Virtually all procedures done at the present
in
a
time are stimulations, more commonly
preponderance of cholinergic activity which
known as deep brain stimulation, rather than
may be treated with anticholinergic drugs.
ablation or destruction of cells. Stimulation
Anticholinergic drugs (e.g., trihexyphenidyl,
parameters can be adjusted for maximum
benztropine) are thought to restore a
benefit after surgery while the destructive
â&#x20AC;&#x153;balanceâ&#x20AC;? between reduced dopamine and
procedure, once done, cannot be changed
uninhibited cholinergic neurons in the
afterwards to enhance benefit. The three
striatum. They are more useful in alleviating
chief targets of both destructive and
tremor and rigidity than bradykinesia. The
stimulation therapies are the thalamus, the
anticholinergic drugs lessen the tremors and
internal globus pallidus, and the subthalamic
rigidity and afford some improvement of
nucleus. (Golbe, L.I., et.al., 2010)
Parkinson
disease,
there
is
function. However, their potency seems to decrease over time, and increasing the
How to deal with Depression
dosage merely increases side effects such as
Treatment of depression in PD is important
blurred vision, dry mouth, bowel and
because depression has a negative influence
bladder problems, cognitive dysfunction,
on cognitive performance, activities of daily
living, and perceived quality of life in PD
placebo-responses of up to 80%, with no
patients. In principle, the same guidelines
significant difference in response between
for the treatment of depression apply for PD
the
patients as for somatically healthy patients.
(Leentjens A.F.G., 2004)
active
and
placebo
conditions.
In case of mild depression, the treatment of choice is supportive psychotherapy, which
A double-blind, placebo-controlled study of
addresses problems with accepting the
nortriptyline that followed a crossover
diagnosis,
the
design also reported a high placebo-
emotional consequences for the patient and
response. The place of other antidepressants,
the partner of having to deal with the
such as the reversible monoamine-oxidase-A
diagnosis. Furthermore, it may stimulate the
(MAO-A) inhibitors, also remains uncertain
patient to do physical exercise and engage in
due to lack of evidence. Apart from the
social activities. In case of more severe
SSRIs, the APA treatment guideline advises
depression, pharmacological treatment is
bupropion, a dopamine reuptake inhibitor, as
warranted.
support,
a first-choice treatment of depression in PD.
counselling and psychotherapy are also
Although this seems a plausible choice from
helpful,
is
a theoretical point of view, there is no
recommended. Individualized psychosocial
evidence for its efficacy in PD, apart from
counselling and structured physical therapy
one open study and a case report. Moreover,
may help patients to identify their problems
bupropion may precipitate a dopaminergic
and concerns and to formulate appropriate
psychosis in PD. (Leentjens A.F.G., 2004)
coping
strategies,
Psychosocial but
further
and
research
coping strategies. (Leentjens A.F.G., 2004; Ferreri F., Agbokou C., Gauthier S., 2006)
Looking at the limited number of studies, and their largely negative results, it is not
However, the efficacy of antidepressant
surprising that 2 systematic reviews have
treatment of depression in PD has never
concluded that there is insufficient evidence
been convincingly established. The only 2
for the efficacy and safety of SSRIs and
published
randomized
tricyclic antidepressants (TCAs) in the
placebo-controlled studies of the efficacy of
treatment of depression in PD, with the
SSRIs, one with citalopram and one with
exception
sertraline, were characterized by very high
nortriptyline. (Leentjens A.F.G., 2004)
double-blind,
of
a
possible
efficacy
of
hypertonia,
myoclonia,
autonomic
There are case reports and case series
symptoms, hyperthermia, and hallucinosis.
describing
and
In extreme cases, this may lead to death. In
interactions of SSRIs. SSRIs may have a
this respect, SSRIs appear to be safer than
negative influence on motor symptoms. The
TCAs. (Leentjens A.F.G., 2004)
potential
side
effects
incidence of this side effect is unknown, but clinically it is not presumed very important.
Having addressed these issues, the question
Practice guidelines favor treatment with an
remains how to deal with depressed PD
SSRI over treatment with TCA because the
patients in clinical practice. Even in the
risk of impairment of motor function is
absence of scientific evidence for the
considered less a problem than the potential
specific
negative
and
antidepressant treatment, clinical evidence
perception because of the anticholinergic
shows that the patient may still benefit from
properties of TCAs. All drug treatments
antidepressant
were generally well tolerated. Common side
absence of better options, a trial-treatment
effects for the SSRIs group included nausea,
with an antidepressant is useful. Both the
fatigue/asthenia and diarrhea, for the TCAs
APA and the American Academy of
group dry mouth, somnolence, constipation
Neurology (AAN) favor treatment with an
and orthostatic hypotension. Nortriptyline
SSRI over treatment with a TCA. (Leentjens
could increase the P–R interval, QRS
A.F.G., 2004)
influence
on
cognition
therapeutic
activity
treatment.
Thus,
of
in
the
duration, and Q–Tc interval and had been associated
with
cardiac
arrhythmias.
The antidepressant dose should be low
(Leentjens A.F.G., 2004; Liu J., Dong J.,
initially
and
Wang L., Su Y., Yan P., Sun S., 2013)
monitoring the dose, the physician should examine
increased
vital
signs,
gradually.
For
symptoms
of
with
the
and
drug
SSRIs and TCAs may give rise to a
depression,
“serotonergic syndrome” when used in
antidepressant,
conjunction with selegiline, an irreversible
interactions. Patients should be followed
MAO-B inhibitor used in the treatment of
closely (e.g., weekly or biweekly) until their
motor symptoms of PD. Such a serotonergic
neuropsychiatric condition is stable. Major
syndrome
risk factors for side effects include advanced
is
characterized
by
tremor,
compliance side
effects
age, high medication doses, prolonged duration of antiparkinsonian treatment and
Conclusion
polypharmacy. (Ferreri F.et.al., 2006)
Effectively caring for the patient with Parkinson’s
disease
requires
careful
Electroconvulsive therapy (ECT) remains an
monitoring of drug treatment, emphasis on
option for the treatment of depression in PD.
teaching
A number of case reports and case series
psychological support.
describe beneficial effects on depression in PD, without negative side effects, and often even temporary improvement of motor symptoms. (Leentjens A.F.G., 2004)
self-reliance,
and
generous
Here are some of the nursing considerations toward patient with PD (McCann J.A.S., et.al., 2011) : 1. Monitor drug treatment and adjust
The first step in the successful management
dosage, if necessary, to minimize
of depression in Parkinson’s disease is to
adverse effects
optimize dopaminergic therapy for improved
2. If the patient has surgery, watch for
motor symptoms. Furthermore, levodopa,
signs of haemorrhage and increased
dopamine
are
intracranial pressure by frequently
believed to have mild antidepressant effects
checking level of consciousness and
and have been studied as antidepressants. In
vital signs
clinical practice, the decision to initiate
3. Encourage
agonists
and
selegiline
independence.
The
antidepressant therapy is based on many
patient with excessive tremor may
factors, including clinical findings, the
achieve partial control of his body by
probability
symptoms
sitting on a chair and using its arm to
worsening without therapy and the patient’s
steady himself. Advise the patient to
likely acceptance. When in doubt, a
change position slowly and dangle
psychiatric consult is recommended. Close
his legs before getting out of bed.
communication
Remember that fatigue may cause
of
depressive
between
the
physician
treating the Parkinson’s disease and the
him to depend more on others
mental health team is especially important
4. Help the patient overcome problems
for the patient’s care. (Ferreri F., et.al.,
related to eating and elimination. For
2006)
example, if he has difficulty eating,
offer
supplementary
or
small
frequent meals to increase caloric
References 1. Beyondblue: the national depression
intake. Help establish a regular
initiative
bowel routine by encouraging him to
Parkinson’s disease, depression and
drink at least 2 L of liquids daily and
anxiety: fact sheet 32. Australia:
eat high-fibre foods. He may need an
Beyond Blue Ltd.
elevated toilet seat to assist him from a standing to a sitting position.
(Australia).
2. Ferreri F., Agbokou C., Gauthier S. (2006).
5. Give the patient and his family
(2011).
Recognition
management
of
and
neuropsychiatric
emotional support. Teach them about
complications in Parkinson’s disease.
the disease, its progressive stages,
Canadian
and adverse drug effects. Show the
Journal, 175(12), 1545-1552.
family how to prevent pressure
Medical
Association
3. Golbe, L.I., Mark, M.H., Sage, J.I.
ulcers and contractures by proper
(2010).
positioning. Inform them of the
Handbook.
dietary
Disease Association, Inc. 21-25.
restrictions
levodopa
Parkinson’s
Disease
American
Parkinson
imposes, and explain household
4. Hales M, Bullock S. Principles of
safety measures to prevent accidents.
pathophysiology. Australia: Pearson;
Help the patient and his family
2013.p.315-6
express their feelings and frustration
5. Leentjens,
A.F.G.
(2004).
about the progressively debilitating
Depression in Parkinson’s disease:
effects of the disease. Establish long-
conceptual
and short-term treatment goals and
challenges : J Geriatr Psychiatry
be aware of the patient’s need for
Neurol, 17, 120-126.
intellectual
stimulation
issues
and
clinical
and
6. Liu J., Dong J., Wang L., Su Y., Yan
diversion. Refer the patient and his
P., Sun S. (2013). Comparative
family to the National Parkinson
efficacy
Foundation or the United Parkinson
antidepressants
Foundation for more information.
disease: a network meta-analysis.
and
acceptability in
PloS ONE, 8(10), 1-9.
of
Parkinson’s
7. McCann JAS, Moreau D, Robinson JM.
Professional
pathophysiology. States
of
3rd
America:
guide ed.
to
United
Lippincott
Williams & Wilkins; 2011.p.299301.
8. Porth, C.M., Gaspard, K.J., Noble K.A.
(2007).
Essentials
pathophysiology.
of 3thed.
Philadelphia : Lippincott Williams and Wilkins, 1044-1045
LITERATURE REVIEW Weight Bearing Exercises to Reduce the Risk of Fracture in Elderly Patient with Osteoporosis El-nissi1, Kezia Joselyn1, Stefina Gunawan1 1
Faculty of Medicine, Kristen Krida Wacana University (AMSA-Ukrida) Abstract
Osteoporosis is defined as a skeletal disease, characterized by low bone mass and microarchitectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture. Osteoporosis is considered to be primary type I (postmenopausal), type II (senile or age related), or secondary which has underlying etiology. It has been estimated that there are already over 200 million osteoporotic people in the world today: one in three women and one in eight men. Normally, bone is remodeled continuously by osteoclasts for resorption and osteoblasts for formation of new bone. Osteoporosis type II happens because of an imbalance between resorption and formation processes of bone in which the resorption exceeds formation. Diagnosis of osteoporosis is done by assessment of bone mineral density (BMD) through a Dual-Energy X-ray Absorptiometry (DEXA) scan while the risk of fracture can be assesed by Fracture Risk Assessment Tool (FRAX). Osteoporosis leads to risk of falls and fractures. In elderly patient, falls often lead to fractures that can have numerous effects of function and quality of life. Weight-bearing exercises such as jogging, walking, stair climbing, dancing, and soccer force bones and muscles to work against gravity. Spesific weight-bearing exercises in three key fracture sites (wrist, hip, and spine) have shown tremendous improvement of boneâ&#x20AC;&#x2122;s resistance and consequently reduce the risk of fracture.! Keywords : elderly, fracture, osteoporosis, weight-bearing exercises
Introduction
deterioration of bone tissue, with consequent
With age, musculoskeletal tissues become
increase in bone fragility and susceptibility
less well adapted for their functions. Thus,
to fracture.1 Moreover, the disease defined
bones become fragile and body composition
as the state of having bone mineral density
changes with the tendency to central fat
(BMD) greater than 2,5 SD below peak
redistribution. These age-related changes
adult bone mass, whether or not the fragility
and processes translate to alterations in bone
has occurred. This disease is a quiet,
properties and muscle power and strength
insidious condition which only manifests
leading to reduced physical performances,
itself in later period of life in the form of
disability, increased risk of fall-related
low impact fracture in certain parts of body,
injury, and the worst case leads to
such as hip and spine.4
mortality.1 Nowadays, one of big public health problems especially for elderly
Osteoporosis is considered to be primary or
people is osteoporosis. Osteoporosis is now
secondary.
also identified as one of 10 most important
idiopathic in etiology contrast to secondary
conditions affecting the entire human race,
which has underlying etiology. Primary
along with other such as cardio-vascular
osteoporosis,
disorders, hypertension, stroke, and diabetes
osteoporosis, occur in 95% of osteoporosis
mellitus and it is important to take into
cases. There are two main clinical types of
consideration that each of these diseases is
primary osteoporosis: (a) postmenopausal
itself a risk factor for osteoporosis.2
and
(b)
Primary
also
osteoporosis
called
senile
or
Postmenopausal
is
involutional
age
related.
osteoporosis
is
The term of ‘osteoporosis’ means ‘porous
characterized by accelerated bone loss,
bone’ and initially implied a histologic
mainly occur in tubular bones, caused by
diagnosis, and later refined to mean bone
factors
that was normally mineralized, but reduced
osteoporosis is characterized by slowly
in quantity.3 Based on World Health
progressive bone loss, mainly cortical, and is
related
to
menopause.
Senile
Organization (WHO), Osteoporosis defined
caused by factors related to aging.5 Though
as a skeletal disease, characterized by low
secondary osteoporosis only compromise
bone
about 5% of all osteoporosis cases, but are
mass
and
micro-architectural
responsible
for
about
20%
of
all
osteoporotic fractures. Some of the most
estimated that there are already over 200
common causes of secondary osteoporosis
million osteoporotic people in the world
are
today: one in three women and one in eight
hypogonadism,
medications,
hyperthyroidism, vitamin D deficiency,
men.
primary hyperparathyroidism, solid organ
significant consequence of osteoporosis.
transplantation,
Three main typical sites of osteoporotic
and
idiopathic
hypercalciuria.6
Fracture of a bone is the most
fracture are hip, spine, and wrist. 70% cases of fracture that occur in US patients aged
Because
osteoporosis
is
so
common,
physicians of almost every specialty will see
over
45
years,
are
attributable
to
2
osteoporosis.
patients with osteoporosis in their practices, though most of them may go unrecognized
Pathophysiology
and
of
Osteoporosis is the reduction in skeletal
osteoporosis patient suffer multiple fracture
mass because of an imbalance between bone
as the result of their osteoporosis. Many of
resorption and bone formation leads to risk
these patients will experience fractures as a
of falls and fractures.7,8 There are two most
result
Later
important factors for osteoporosis: loss of
osteoporotic patient will need to deal with
gonadal function and aging. Normally, bone
the adverse outcomes that can happen,
is remodeled continuously by osteoclasts
including death, disability, and a reduced
which resorb the old bone, and osteoblasts
quality of life. Solution to reduce the risk of
which build a formation of new bone to
fracture is considered important to prevent
renew
untreated.
of
their
There
are
many
osteoporosis.
multiple fractures that can lead to mortality.
4
the
It is estimated that 44 million people suffer from osteoporosis in the US alone, as do equally high percentage of the population in many countries spread from the Americas, Asia, and Europe. Furthermore, it has been
and
maintain
its
anatomical and structural integrity. In normal
Epidemiology
skeleton
conditions,
bone
remodeling
proceeds in cycles in which osteoclasts attached to bone and thereafter remove the bone
by
acidification
and
proteolytic
digestion. Shortly after the osteoclasts have left the resorption site, osteoblasts invade the area and begin to form new bone by
secreting osteoid, create mineralized bone.
osteoporosis
in
elderly
age.
Third,
After bone formation has stopped, lining
insufficiency of vitamin D may be increase
cells cover the surface of the bone.
the risk of osteoporosis. Fourth, estrogen deficiency disrupts the activation of new
The pathogenesis of osteoporosis is one or combinations of increases in bone resorbing factors, loss of inhibitors of resorption, increases in inhibitors of formation, loss of stimulators of bone formation, with the other critical factor: peak bone mass.9 Peak bone mass is the amount of bone mineral at the end of the growth, shows the peak skeletal mass and density.10 The greater the amount of bone achieved during the peak period, the lower the chance that a person will develop osteoporosis later in life.8 The pathogenesis of osteoporosis may be seen in eight ways. First,
increased
remodeling
sites
recruitment creates
a
of
bone
reversible
reduction in bone tissue, but also results in permanent loss of tissue and makes the
bone remodeling sites and exaggeration of the imbalance between bone formation and resorption. Fifth, bone mass are stimulated by physical activity and the best time to stimulate the bone mass is during growth and before the age of puberty. Sixth, various genetic
and
acquired
diseases
may
contribute to bone loss, from multiple factors such nutrition, reduced physical activity, and factors that affect rates of bone remodeling. Next, a large number of medications may effect on the skeleton such as glucocorticoids and thyroid hormone. Last, cigarette consumption effects bone mass because the toxin in cigarette affects the
osteoblast
metabolism.
or
modifying
estrogen
8
skeletal structure disrupted. If the osteoclasts penetrate trabeculae, they leave no space for
There
are
new bone formation to occur, thus rapid
osteoporosis: primary osteoporosis (type I
bone loss occurs and impairs the cancellous
and type II) and secondary osteoporosis.
connectivity. In cortical bone, increased
Osteoporosis related to aging has been
activation of remodeling creates more
classified as primary osteoporosis type II,
porous bone, leads to the decrease of bone
namely senile osteoporosis, affects cortical
strength. Second, inadequate calcium intake
and
during growth may impair the peak bone
primary osteoporosis type I, which affects
mass and leads to increased risk of
mostly trabecular bone, is related to
trabecular
two
bone.
classifications
Meanwhile,
of
the
menopause and is termed as postmenopausal
cause of bone loss in elderly is the
osteoporosis. The other causes such as
differentiation of cells of the osteoclastic
corticosteroid use or endocrinopathy are
lineage may be increased with age, therefore
classified as secondary osteoporosis. Both
maintaining high rates of bone resorption.8
types can increase the risk of fracture in cancellous bone, such as osteoporotic vertebral compression, distal radius, or intertrochanteric hip fractures. On the other hand, patients with type II disease may be at greater risk of fractures through cortical bone, such as the femoral neck, pelvis, proximal humerus, and proximal tibia.11
Progressive dietary calcium is probably the cause of type 2 disease.11 Appetite becomes suppressed along with aging which leads to lower intake of foods that rich in calcium. This
factor
contributes
to
states
of
malnutrition in elderly people. Bone mass is positively affected by mechanical loads, explaining why progressive inactivity may
Primary osteoporosis type 2 has different
contribute to osteoporosis. Mostly, people
characteristics from primary osteoporosis
become less active along with aging which
type 1.7,11 Bone loss in elderly happens
potentiate progressive bone loss. The pain of
because
and
an osteoporotic compression fracture causes
formation processes of bone which the
more inactivity, which this inactivity can
resorption exceeds the formation. The
lead to further bone loss, more fractures, and
amount of bone formed during each
more pain and inactivity, make this process
remodeling
a vicious cycle.11
of
imbalance
cycle
resorption
decreases
with
age
because of the reduction of the osteoblast supply and increased osteoclasts activity.7,11 Osteoporosis in elderly may be caused by
Clinical Manifestations
the decrease of the bone marrow cellular
Osteoporosis leads to fractures that can have
activity. Research shows that in elderly
tremendous effect of function and quality of
mice, there is a dramatic decrease in the
life. There are many sides of osteoporosis
numbers of fibroblast and osteoblast formed
related fractures but hip fractures and
in marrow cultures, making a conclusion
vertebral fractures are the most common and
that there is an impairment of marrow ability
disabling.12
to produce osteoblast precursors. The other
the other cause besides osteoporosis must be Hip fractures can be devastating and require surgical intervention for proper healing. Half
considered if a solitary vertebral fracture is found above the 7th vertebra.13
of the patients can lose their ability to walk independently and over half of same people will need assistants in their basic daily life activities. Furthermore, up to one-third of people who suffer an osteoporotic hip fracture will be dead within a year.12
Diagnosis Bone mineral density (BMD) is the major criteria for the diagnosis and monitoring of osteoporosis.
WHO
(1994)
defines
osteoporosis based on the bone mineral density, which is reported in a form of a T-
Vertebral fractures appear on radiographs as
score. The T-score is the number of standard
compression
reduce
deviations from which the individual differs
13
from the peak bone mineral density for
Although two-thirds of vertebral fractures
young adults of the same sex. For each
are clinically silent, they are associated with
standard deviation below the average, the
a two to threefold increased risk of
risk of fracture is approximately doubled:14
additional fractures. Chronic back pain,
* T-score between -1 and -2.5 indicates
height loss, arm span-height differential, and
osteopenia.
deformities
that
vertebral body height by 20% or more.
thoracic kyphosis are all sequel of vertebral compression fractures. As a result of abdominal contents being compressed into
*
T-score
of
-2.5
or
less
indicates
osteoporosis.
less vertebral space, patients may notice a
* T-score of -2.5 or less with evidence of a
protuberant belly, early satiety, constipation
fragility
or pain in their neck muscles as they have to
established osteoporosis.
fracture
may
be
defined
as
constantly extend their neck. Kyphosis can also lead to dyspnea and a restrictive defect on pulmonary function testing. De Smet et al. found that solitary wedge fractures did not occur above the 7th thoracic vertebra in a study of 87 osteoporotic women. Therefore,
The
dual-energy
X-ray
absorptiometry
(DEXA) scan is the most commonly used imaging technique to measure BMD due to its precision, reliability, short scanning time and its ability to measure BMD at different
sites. The sites suitable for DEXA scanning
osteoporotic fracture can be estimated using
include anterior and/or posterior lumbar
the World Health Organization (WHO)
spine, proximal femur, distal forearm and
Fracture Risk Assessment Tool (FRAX).17 It
whole body. BMD differs between the sites
is freely available online and consists of a
of the body, and there is only a moderate
simple set of 12 questions regarding their
correlation between bone mineral density at
risk factors. But it is important to take not
different location. Therefore, measuring
that FRAX tool has several limitations.
BMD of a specific site is the best predictor
Although FRAX is an international tool, it is
of fracture for that particular site.
14
For
only suitable for use in countries for which
diagnosis, measurement at the hip is the gold
epidemiological
standard in terms of scanning site since it
Furthermore, only femoral neck BMD is
has the highest predictive value for hip
taken into account by FRAX. Moreover, the
fracture, which is the most severe form of
FRAX tool can only be used to asses a
complication in osteoporosis and predicts
patient
who 18
data
has
are
not
been
available.
treated
risk of all fractures as well as other
previously.
If Frax highlights a risk, the
techniques.15
patient should be advised to see their health care practitioners for a full assessment
The clinical consequence of osteoporosis is
including a DEXA scan.15
the fractures that appears. Therefore, there is a great interest in the use of bone mineral
Treatment
measurement to predict the likehoodness of
To treat osteoporosis, the U.S. Food and
fractures.
16
BMD on its own is not a good
Drug Administration (FDA) has approved
measure of fracture risk since there are so
several medications to slow or stop bone
many other contributing factors, such as
loss, reduce the risk of fractures, or rebuild
previous fractures, family history, other
the bone.19
medical conditions, medications, smoking, alcohol and weight.15 Bisphosphonates
are
in
the
class
of
antiresorptive agents with purpose to slow For men and women of age 40 until 90, their
bone remodeling and increase bone density.
10-year probability of hip and major
Alendronate and risedronate reduce fracture
risk of vertebral, hip, and wrist by 40%-50%
Calcitonin-salmon is not widely used but
over 2-4 years, while ibandronate reduces
helps with a modest reduction in risk of
vertebral fractures, possibly by as much as
vertebral fractures and may relieve pain
50% over 3 years. Zoledronic acid is able to
associated with bone fractures. Selective
increases bone density and reduces fractures
estrogen
receptor
in the hip, spine, and non spine areas (such
vertebral
fractures
as the wrists and arms). One major study
increasing bone density in a different rate as
shows that zoledronic acid reduced the risk
bisphosphonates.19
modulators by
reduces
40%-50%
by
of spine fractures by 70% and hip fractures by 41%.19
Parathyroid
hormone
reduces
vertebral
fractures by 65%-70% and decreases the risk There are several side effects of all the
of nonvertebral fractures by about 50% by
bisphosphonates (alendronate, ibandronate,
doubling the rate of bone formation. Even
risedronate, and zoledronic acid) such as
though in some studies parathyroid hormone
bone, joint, or muscle pain. Side effects of
- treated rats developed a form of bone
the oral tablets may include nausea,
cancer, there has been no evidence of this
difficulty swallowing, heartburn, irritation of
risk in human. Dizziness and leg cramp are a
the esophagus, and gastric ulcer. Flulike
few of the side effects, and modest
symptoms, fever, pain in muscles or joints,
elevations in serum and urine calcium can
and headache are side effects that can occur
occur.19
shortly after receiving the first dose of intravenous biphosphate. These side effects usually stop within 2-3 days and do not happen with future infusions.19
Other
bone-sparing
treatments
include
calcium and vitamin D, and a new sixmonthly injection denosumab, which is a type of monoclonal antibody that works by
For bisphosphonates to be effective, a good
targeting a protein that controls the activity
dietary intake of calcium and vitamin D is
of osteoclasts and in turn prevents bone cells
essential. Vitamin D deficiency must be
being broken down. Other available options
treated before starting bisphosphonates or
are synthetic parathyroid hormone injectable
any osteoporosistreatments.15
treatments such as teriparatide, which works
by mimicking the hormone and are used to
Prevention of Fracture
increase bone formation.15
Later in life of an osteoporotic patient, it is important to prevent falls. Falls lead to
Patients who have been assessed and given
fractures that can have numerous effects of
treatment are at risk of fracture, so their
function and quality of life.13 A study shows
compliance is important. Pharmacists who
that
are administering an osteoporosis treatment
focusing in building bone in three key
for the first time, have to ensure the patient
fractures sites - wrist, hip, and spine â&#x20AC;&#x201C; is
understands that, if they have problems, they
proven to be beneficial. Before, it was
should talk to the pharmacist or their health
thought that all types of exercises were
care practitioners rather than just stop their
helpful, but this study shows that the
treatment.15
essential ones are resistance and weight-
specific
weight
bearing
exercises
bearing.20
Patients being considered for treatment should also be counseled on risk factor
Resistance exercises use muscular strength
reduction. They should be made aware on
to promote muscle mass and strengthen
the importance of calcium, vitamin D, and
bone. By doing weight-lifting, muscles are
exercise as part of any treatment program
forced to become stronger. Since tendons
for osteoporosis.19
are attached to the bone, they stress the bone and stimulate more osteoblasts to grow. Meanwhile, in weight-bearing exercises,
For
it
to
be
effective,
osteoporosis
bones and muscles are pushed to work
medication must be taken continuously for a
against gravity.! Since gravity is holding
minimum of 6 months. The choice of
them down, endurance is required to move
medication should be made between the
muscles and bones against it.21 Bone is
healthcare provider and the patient and
mechanosensitive, therefore a sufficient
should be based on the individual patient.
19
magnitude of the external forces loaded upon the bone via exercise is needed to create a fluid flow within the lacunarâ&#x20AC;&#x201C; canalicular network to stimulate bone
formation.22 Mechanical loading stress on
be held for at least 6-8 months to fully
bone causes tissue deformation within bone
obtained the potential changes in structural
that stimulates the bone to adapt by
properties.22
remodeling to oblige these demands, and
Conclusion
ultimately improve boneâ&#x20AC;&#x2122;s resistance to fracture.23 Weight-bearing exercises include jogging, walking, stair climbing, dancing, and soccer. 21
Osteoporosis is one of big public health problems for elderly people and now identified as one of 10 most important conditions affecting the entire human race. Treatment of osteoporosis includes several
Weight-bearing exercise is considered to be
medications and a series of ways to reduce
more effective than resistance exercise
risk
because its routine can be incorporated with
osteoporosis, falls lead to fractures that can
daily activities such as rising from a chair or
have numerous effects of function and
stair climbing. On the other hand, one study
quality of life. Weight-bearing exercises -
indicates
high-impact
jogging, walking, stair climbing, dancing,
exercise, such as jumping, may cause
and soccer â&#x20AC;&#x201C; have shown tremendous
reduction
in
In
improvement of boneâ&#x20AC;&#x2122;s resistance and
summary,
the
a
consequently reduce the risk of fracture.
that
intensive regional study
bone
mass.
suggests
that
combined weight-bearing training program,
factors.
In
elderly
patients
with
(Figure 1)
without jumping activities but including strengthening, coordination
aerobic, exercises,
balance might
and reduce
Reference
fracture risk factors by improving bone
1. Guglielmi, G., Peh, W. C. G.,
density as well as neuromuscular functions
Guermazi A (Eds). (2013). Geriatric
associated with the risk of falls.24
imaging.
Berlin:
Springer-Verlag
Berlin and Heidelberg GmbH & Co. K It takes around 3-4 months for the
2. Bartl,
R.,
Frisch,
B.
(2009).
completion of the bone remodeling cycle
Osteoporosis: diagnosis, prevention,
(bone
therapy. (pp. 2). Berlin: Springer-
resorption,
formation,
and
mineralization). Therefore, training should
Verlag Berlin and Heidelberg GmbH
bone
& Co. K
Journal, 12,
3. Arden, N. (2006). Osteoporosis. (pp. 5). London: Remedica 4. Cooper,
C.,
strength.
European
Spine S90-6.
doi:http://dx.doi.org/10.1007/s00586 -003-0603-2
Gehlbach,
S.
H.,
9. Karnik, A. A., & Von Feldt, J.,M.
Lindsay, R. (2005). Prevention and
(2008).
treatment
a
elderly. Aging Health, 4(4), 351-363.
clinicianâ&#x20AC;&#x2122;s guide. (pp. 11). New
doi:http://dx.doi.org/10.2217/174550
Yorkshire: Taylor & Francis
9X.4.4.351
5. Chew,
F.
of
S.
osteoporosis:
(2010).
Skeletal
Osteoporosis
in
the
10. Marcus, R., Feldman, D., Nelson, D.
radiology: the bare bones. (pp. 276).
A.,
Rosen,
Philadelphia: Lippincott Williams &
Osteoporosis.
Wilkins
London: Elsevier
C.
J.
(pp.
(2008). 973-979).
6. Camacho, P. M., Miller, P. D.
11. Daly, R. M., Petit, M. A. (2007).
(2007). Osteoporosis: a guide for
Optimizing bone mass and strength:
clinicians. (pp. 81). Philadelphia:
the role of physical activity and
Lippincott Williams & Wilkins
strength. (pp. 64-66). Basel: Karger;
7. Epstein, F. H., M.D., Manolagas,
2007
Stavros C,M.D., PhD., & Jilka, R.
12. Lindsay, R., Cosman, F. (2012).
L., PhD. (1995). Bone marrow,
Osteoporosis. In Longo, D. L.,
cytokines, and bone remodeling:
Fauci, A., Kasper, D., Hauser, S.,
Emerging
the
Jameson, J. L., Loscalzo, J. (Eds.),
pathophysiology of osteoporosis. The
Harrisonâ&#x20AC;&#x2122;s principles of internal
New
of
medicine volume 2 (18th ed.). (pp.
305-311.
3120-3125). New York: McGraw-
insights
England
Medicine, 332(5),
into Journal
Retrieved
from
http://search.proquest.com/docview/ 223981062?accountid=50673 8. Bono, C. M., & Einhorn, T. A. (2003). Overview of osteoporosis: Pathophysiology and determinants of
Hill Companies 13. Stone, L. M., & Lyles, K. W. (2006). Osteoporosis
in
later
life. Generations, 30(3),
65-70.
Retrieved
from
http://search.proquest.com/docview/
Nursing, 30(3), 162-71; quiz 172-3.
212190921?accountid=50673
Retrieved
14. Walker, J. (2008). Osteoporosis: Pathogenesis,
diagnosis
and
management. Nursing
from
http://search.proquest.com/docview/ 880947384?accountid=50673 20. Osteoporosis;
weight-bearing
Standard, 22(17), 48-56; quiz 58.
regimen, calcium citrate proven to
Retrieved
increase
from
bone
mineral
density.
http://search.proquest.com/docview/
(2006). Physician Law Weekly, 330.
219841653?accountid=50673
Retrieved
15. UPDATE:
Osteoporosis.
(2012). Chemist & Druggist, , 13n/a.
Retrieved
from
from
http://search.proquest.com/docview/ 230775133?accountid=50673 21. American Council on Science and
http://search.proquest.com/docview/
Health. (2005). The prevention and
1115107364?accountid=50673
treatment of osteoporosis. (pp. 28).
16. Kanis, J. A. (2002). Diagnosis of osteoporosis
and
assessment
of
fracture risk. The Lancet, 359(9321), 1929-36.
Retrieved
from
New York: American Council on Science and Health 22. Marques, E. A., Mota, J., Machado, L., Sousa, F., Coelho, M., Moreira,
http://search.proquest.com/docview/
P.,
199018009?accountid=50673
Multicomponent training program
17. Reid, D. M. (2011). Handbook of osteoporosis.
(pp.
57).
London:
Springer Healthcare Ltd
&
Carvalho,
J.
(2011).
with weight-bearing exercises elicits favorable
bone
density,
muscle
strength, and balance adaptations in
18. Bhandari, M., Adili, A., Bryant, D.,
older
women. Calcified
Tissue
et al. (ed). (2012). Evidence-based
International, 88(2),
orthopedics.
doi:http://dx.doi.org/10.1007/s00223
(pp.
41-42).
West
Sussex: Blackwell Publishing
117-29.
-010-9437-1
19. Kamienski, M., Tate, D., & Vega, M.
23. Shaw, S. E. W. E. S. C. M. M.
(2011). The silent thief: Diagnosis
(2006). Adaptations in cortical and
and
trabecular
management
osteoporosis. Orthopaedic
of
bone
in
response
to
mechanical loading with and without
weight
bearing. Calcified
International, 79(6),
Tissue 395-403.
doi:http://dx.doi.org/10.1007/s00223 -005-0293-3 24. Englund, U., Littbrand, H., Sondell, A., Pettersson, U., & Bucht, G. (2005). A 1-year combined weightbearing
training
program
is
beneficial for bone mineral density and neuromuscular function in older women. Osteoporosis International,16(9),
1117-23.
doi:http://dx.doi.org/10.1007/s00198 -004-1821-0
Tables and figures
Figure 1. Normal (a) and osteoporotic (b) trabecular network of bone.2
LITERATURE REVIEW
Combination of SNCA Gene Small Interfering RNA (siRNA) and APO!4 Single Strand All-DNA Oligonucleotides (ssODNs): A New Insight into Treatment of Motoric and Cognitive Impairment in Parkinson’s Disease (PD) Mochamad Iskandarsyah Agung Ramadhan1, Janice Tanumihardja1,Filbert Riady Adlar1 1
Faculty of Medicine, University of Indonesia (AMSA-UI) Abstract
Parkinson’s Disease (PD) is the second most prevailing progressive neurodegenerative disease of the elderly, and 0.4% of Indonesians were diagnosed with PD, and the death rate was ranked 5th in Asia and 12th globally. Characteristic features of PD involving the motoric and non-motoric symptoms, especially the decline of cognitive function. There is no known definite treatment for PD that can stop the progression; all PD patients are to take even only the motoric symptomatic medicine throughout their lives. Therefore, there is a need to produce effective drugs to treat the cause and symptoms of PD –motoric and non-motoric. Gene therapy seemed to be consideration in making effective drugs for PD. We will discuss gene therapy modalities for PD patient by combining SNCA gene silencing with siRNA to retard PD progression, along with the correction of APO$"4 with single strand all-DNA oligonucleotides (ssODNs) to prevent dementia development. This scientific paper is based on literature review with specialty in biomolecular medicine and biomaterial which discuss about the designation of PD based on combination of siRNA and ssODNs carried by PEG-PEI given transnasally. The literature searching was based on scientific journal database such as PubMed and Cochrane. From the multiple filter process, we finally found 54 journals with 12 key articles. 18 articles are article review and the rest are experimental with 1 article is clinical trial. Articles we found not only based health, biomolecular, and biomaterial approach regarding the topic. Combination of siRNA for SNCA genes and single-stranded all-DNA oligonucleotides (ssODNs) in APO%4 conversion to APO%3, given with modified high molecular weight (HMW) polyethylene glycol-polyethyleneimine (PEG-PEI) as the vector transnasally can be effective modality to treat the cause and symptoms of PD with high transfection and low toxicity.
Keywords: APO%4 Conversion, Parkinson Disease, Polyethylene Glycol-Polyethyleneimine (PEG-PEI), Single Strand All-DNA Oligonucleotides (ssODNs), Small Interfering RNA (siRNA), SNCA Gene, Transnasal Route
the
disease
progresses,
non-motoric
Introduction
symptoms become apparent and dementia is
Ever since its discovery in 1817 by James
one of them. Studies by Aarsland and Kurz
Parkinson, Parkinsonâ&#x20AC;&#x2122;s Disease (PD) has
(2010) shown that about 30% to 40% of PD
been an important geriatric pathology.
patients experience dementia in their course
Currently PD is the second most prevailing
of disease. Progression to dementia is
progressive neurodegenerative disease of the
important because dementia will make
elderly, and the increasing number of cases
tending
was estimated to be doubled by 2030
challenging. Other non-motoric symptoms
(Thomas & Beal, 2007; Mosley, Hutter-
of
Saunders, Stone, & Gendelman, 2012; Tan,
depression, and anxiety which are difficult
2013). About 1-2% of world population
to detect due to the comorbidities and the
above the age 50 is affected by this currently
condition of patients (Mercury, Tschan,
incurable condition (Thomas & Beal, 2007).
Kehoe, & Kuechler, 2007; Thomas & Beal,
According to studies conducted in Asia, the
2007).
PD
to
PD
include
patients
even
autonomic
more
symptoms,
incidence of PD escalates as the age increases above 40 years old (Muangpaisan,
Less than 10% of PD is of familial origin,
Hori, & Brayne, 2009). In 2002, about 0.4%
while the rest are sporadic and may affect
of Indonesians were diagnosed with PD, and
anyone (Thomas & Beal, 2007). So far,
the death rate was ranked 12th globally and
there is no known definite treatment for PD
ranked 5th in Asia (Noviani, Gunarto, &
that can stop the progression; all PD patients
Setyono, 2010).
are
to
take
symptomatic
medicine
throughout their lives (Luk & Lee, 2014). At PD is caused by loss of dopamine neurons
the early stage of the disease, dopamine
induced by accumulation of protein called
agonists are recommended. However, the
the Lewy body (Luk & Lee, 2014; Liu et al.,
administration of the drug is not without
2013).
PD
side effects, and truthfully many patients
involving the motor system are known as
withdraw from taking the drug because of
TRAP: tremor at rest, rigidity, akinesia, and
them (Parkinson Study Group, 2000).
postural instability (Jankovic, 2007; Brichta,
Another common drug is levodopa. Despite
Greengard, & Flajolet, 2013). However as
its high potency, this drug is apparently
Characteristic
features
of
more hideous as not only will long term
In this paper we will discuss the designation
administration lead to decreased efficacy,
of a gene therapy for PD patient by
but it will also cause dyskinesias (Parkinson
combining SNCA gene silencing with
Study Group, 2000; Brichta et al., 2013).
siRNA to retard PD progression, along with
Some
as
the correction of APO$"4 to prevent
pallidotomy, thalamotomy, and Deep Brain
dementia development. Our aim is to come
Stimulation (DBS) are currently available,
up with a medication that may cure PD
but they require strict conditions for the
patient completely once and for all. We hope
candidates
conveys
that this paper will increase the awareness of
dangerous risks (Okun, 2014; Honey &
medical students to the promising research
Palur, 2001).
field of PD treatment.
Some recent researches may give us a hint to
Methods
the future of PD. Liu et al. (2013) explains
This scientific paper is based on literature
the probable benefit of using gene therapy
review with specialty in biomolecular
targeting the inhibition of SNCA gene as PD
medicine and biomaterial which discuss
treatment. Overexpression of SNCA gene is
about the designation of PD based on
thought to be responsible for Lewy body
combination of siRNA and ssODNs carried
formation and neuronal loss, and its
by
translation silencing by small interfering
literature searching was based on scientific
RNA (siRNA) seems to provide protection
journal database: PubMed and Cochrane.
for the neurons. Another study by Tsuang et
We only found source from PubMed, using
al. (2013) reveals that APO$"4 alleles are
keyword â&#x20AC;&#x153;(Parkinson Disease gene therapy)
overexpressed in PD and bear increased risk
and (SNCA Gene Silencing or Small
of dementia development. Previous studies
Interfering RNA or siRNA) or (APO%4
by Papaioannou, Simons, and Owen (2012)
Conversion or Single Stranded All-DNA
results in a promising APO$ alleles
Oligonucleotides or ssODNs) or (Nanogel or
correction by gene therapy to protect the
Polyethylene Glycol-Polyethyleneimine or
cardiovascular system from atherosclerosis.
PEG-PEI) or (Transnasal)â&#x20AC;?.
surgery
and
intervention
procedure
such
PEG-PEI
given
transnasally.
The
We searched for any meta-analysis, clinical trial, experimental study, systematic review, review, and journal; articles from up to 5 years ago are preferred. The searching itself resulted in 1395 articles, then deducted to 305 based on free-full text availability. After did some reduction based on title and abstract
screening
and
exclusions
(Alzheimer Disease, cancer, microRNA, etc), there were 143 articles ready to be progressed at multiple filter. The data itself collected between 13th and 26th December 2014.
Discussion Pathology of Parkinsonâ&#x20AC;&#x2122;s Disease Parkinsonâ&#x20AC;&#x2122;s Disease is a pathology marked by eosinophilic intracytoplasmic protein inclusion, called Lewy bodies (LB) which enlarges
neuritis,
and
significantly
progressive dopaminergic neuron loss from the substantia nigra pars compacta (Thomas & Beal, 2007; Luk & Lee, 2013). The inclusion bodies are found in both familial and sporadic PD (Luk & Lee, 2013). LB is a substance that is mostly made up of #synuclein, a membrane protein consisting of 140 amino acids (Liu et al., 2013; Alafuzoff & Parkkinen, 2013). The protein is a product
Results From the multiple filter process, we finally found 54 journals with 12 key articles. 18 articles are article review and the rest are experimental with 1 article is clinical trial. There are 5 articles which aged more than 5 years. The articles we found not only based on health and biomolecular approach but also biomaterial approach. After decided which articles would be used, we did synthesis and analysis based on the articles provided about the designation of PD based on combination of siRNA and ssODNs carried by PEG-PEI given transnasally.
from the expression of SNCA gene and is normally located within axon terminals. It is believed to function in vesicle recycling (Liu et al., 2013). Mutations in SNCA gene cause the proteins to aggregate into LB. Three missense mutations result in autosomal dominant form of PD in which the soluble #-synuclein undergoes misfolding, thus enhancing the aggregation activities of its hydrophobic domain (Thomas & Beal, 2007). These amyloid fibrils of #-synuclein that will form LB have the ability to induce their related protein to misfold into amyloid fibrils (Luk
& Lee, 2013). Phosphorylation of Ser129
mechanism underlying the loss of motor
also favor #-synuclein aggregation, and
controls (Luk & Lee, 2013).
Ser129 phosphorylated #-synuclein is a major component of LB. Involvement of #-
Dementia starts to emerge at least one year
synuclein in PD pathogenesis has classified
after the appearance of motoric symptoms
PD into the group of synucleinopathies
(Tsuang et al., 2013). The condition would
(Thomas & Beal, 2007).
begin with milder cognitive dysfunction. Pathology behind cognitive dysfunction in
Luk and Lee (2013) postulated that the
PD can be divided into two; the disruption
inclusions are transferred through the axons
of dopamine activities within corticostriatal
of the affected neuron to the neurons in
pathway and LB accumulation in the
connection with it. An important notice is
posterior
that the spread of LB relates to the stages of
secondary to the disease (Nombela et al.,
symptoms that manifest. In the initial stage,
2014). Another risk factor for dementia is
LB affects the nuclei of the lower brainstem,
the presence of APO$4. Research found that
olfactory, and peripheral neurons. In the
in the brain of patient with PD related
subsequent stages, LB disseminates to
dementia,
midbrain which includes the substantia
compared to PD patient without dementia.
nigra, manifesting as motoric symptoms. In
Research shown that APO$4 alters plasticity
the later stage, LB reaches the cortical
of
region, and the non-motoric symptoms such
neurotoxicity properties mediated through
as dementia and hallucination take effects
microgila (Tsuang et al., 2013).
cortex
neurons
with
APO$4
and
cholinergic
is
that
loss
overexpressed
APO$4
has
(Braak et al., 2003). !
Current Management of Parkinsonâ&#x20AC;&#x2122;s
#-synuclein inclusions brings detrimental
Disease and Its Limitations
effects towards the affected neuron. The inclusions cause neurons to degenerate, and most notably it occurs in the substantia nigra. Disruption of dopaminergic neurons within the substantia nigra cut off the innervation of dopamine into the striatum, a
The current treatment of PD is not curative but instead revolves around the alleviation of the symptoms and improving the patientâ&#x20AC;&#x2122;s quality of life. This therapy is life-long and it is important to note that each treatment option should be specifically tailored to the
individual
patient,
targeting
the
most
dyskinesias as well as other non-motor
debilitating symptoms (Jankovic & Aguilar,
manifestations
2008).
Jankovic & Aguilar, 2008; Okun, 2014).
Pharmacological therapy. There are a wide
Many parkinsonologist recommend that
variety
treat
levodopa treatment is to be delayed until the
Parkinsonâ&#x20AC;&#x2122;s disease but nonetheless the
clinical manifestations of PD evidently
levodopa is the most effective drug in the
disturb the normal functioning and lifestyle
control of the symptoms of PD. The gold
of the patient. Instead, dopamine agonist
standard therapy is a regimen that includes
should be prescribed as an early initial
levodopa with the addition of a peripheral
therapy.
(Jankovic
dopa decarboxylase inhibitor, such as
Schapira,
2005).
carbidopa (Jankovic & Aguilar, 2008;
receiving levodopa have a longer period of
Brichta et al., 2013).
extensive
of
drugs
available
to
(Brichta
control
movements,
&
et
al.,
Aguilar,
However, of
delayed
2013;
their
2008; patients motoric
progression
to
Levodopa is the precursor of dopamine and
disability and longer life expectancy in
it would compensate the lack of endogenous
general
dopamine in the brain. The inhibitor
Furthermore, dopamine agonists are more
enhances the therapeutic effects of levodopa
associated
by preventing the peripheral conversion of
hallucinations,
levodopa to dopamine as illustrated in
(Schapira, 2005).
picture
1.
(Jankovic to
the
&
Aguilar,
2008).
development
especially
in
of
elderly
Catechol-o-methyl-transferase
(COMT) inhibitors such as entacapone
Nondopaminergic therapy.
maybe be used as an alternative inhibitor.
Anticholinergic drugs may be used in
(Jankovic & Aguilar, 2008). However, the
alleviating symptoms, such as tremors, in
levodopa therapy itself is unable to relief
the early stages of therapy. Nevertheless,
tremor, postural instability and most of the
limitations to the use of anticholinergic lies
non-motor symptoms (Brichta et al., 2013).
in its side effects which are dry mouth,
Also, the long-term use of levodopa is likely
urinary symptoms and impairing of the
to reduce its efficacy and cause motor
cognitive function. Amantadine can control
complications
the motor symptoms of PD to a certain
like
fluctuations
and
extend and possess anti-dyskinetic effects (Jankovic & Aguilar, 2008; Schapira, 2005).
Patients treated with pallidotomy were
Monoamine oxidase (MAO) B inhibitors
reported to have reduced dyskinesias,
may be used as adjunctive therapy in early
decreased tremor and are less rigid. It is less
and
ideal to give pallidotomy to patients with
late
PD
Anticholinergic
(Schapira,
drugs,
2005).
amantadine
and
Parkinson-plus
syndromes
presenting
hallucinations as side effects (Samuel,
psychiatry or gait problems as primary
Maidment,
issues.
&
Fox,
2006).
speech,
those
MAO-B inhibitors were indicated to cause Boustani,
with
or
Probable
autonomic,
complication
includes
seizure,
of
the
Dementia in Parkinsonâ&#x20AC;&#x2122;s disease. There are
procedure
infection,
limited options of available treatment for
hemorrhage and injury to optic tract or
non-motor symptoms of PD, such as
internal capsule (Honey, Palur, 2001).
dementia. (Schapira, 2005). In particular, the treatment of cognitive impairment primarily
Deep
relies on cholinesterase inhibitors such as
effectively improve most symptoms such as
donepezil, rivastigmine and glantamine
tremor, bradykinesia, gait, speech and
(Jankovic,
dyskinesia. Although the potential of DBS
Aguilar,
2008;
Samuel,
brain
stimulation
(DBS)
can
Maidment, Boustani, & Fox, 2006).
therapy is undeniable, it is a costly process,
Neurosurgical approach. Neurosurgical
requires general anesthesia, needs additional
approach is the last resort in the treatment of
time
PD.
parameters,
Thalamotomy
results
in
the
to
finely and
adjust has
the
stimulation
restricted
battery
improvement of tremor but minimal effect to
strength. Electrical currents from the probe
bradykinesia.
with
may also be transmitted into the surrounding
cognitive impairment, dysarthria or other
and manifest side effects (Okun 2014;
major of PD symptoms aside from tremor
Honey, Palur, 2001).
are
not
the
Patients
ideal
presenting
candidates
for
thalamotomy. Patients may suffer from
Small Interfering RNA (siRNA) for
contralateral
Silencing SNCA Gene Translation
weakness,
dysarthria,
dysphagia and arm and foot ataxia as
Since SNCA gene overexpression results in
complications to the procedure (Honey,
aggregation of excessed &-synuclein and
Palur, 2001).
dopamine neurons loss in PD, SNCA gene
therapy with RNA interferencing method is
aggregation itself. Ectopic silencing is also
now on the focus of curative effort. The
possible as proven by Khodr et al. (2011), in
method allows the prevention of unwanted
which siRNA embedded given was also
protein translation. There are two methods
found on area outside substantia nigra. The
offered by Khodr et al. (2011): two short
sensitivity of SNCA gene in any region
strands of RNA called small interfering
regarding siRNA is varied; with substantia
RNA (siRNA) and hairpin loop structure of
nigra’s sensitivity is higher than striatum –
double stranded RNA called short hairpin
allowing higher toxicity of siRNA in the
RNA (shRNA). Despite shRNA having
region. siRNA targeted to SNCA is also
lower toxicity and can be chronically
improve motor function, even though not via
expressed in the cells, siRNA is preferable
dopamine neuron protection, which fail to
choice for reducing expression of SNCA
show in the study.
genes in PD. The acute effect of SNCA expression by siRNA allows it to commit
Study by McCormack, Mak, Henderson,
the gene function in maintaining synaptic
Bumcrot, Farrer, and Di Monte (2010)
vesicles supplies in presynaptic terminals.
shows that siRNA infused (27 mg/ml in 0,1
Moreover, siRNA has higher likelihood of
M phosphate buffered saline) in substantia
specific “off genes” target than shRNA.
nigra of squirrel monkey (Saimiri scuireus)
Totally interferencing of endogenous SNCA
give positive results in reducing pathology
expression, as studied by Gorbatyuk et al.
of PD. The 21 base pairs of siRNA lower &-
(2010) in rats, resulted in dopamine neuron
synuclein by 40-50% in 2-4 weeks, better
loss and motor deficit.
than control luciferase as evidenced by RTPCR and histology stain (Picture 2). This
siRNA targeted to SNCA gene contributes in reducing &-synuclein in mRNA and protein
level.
Meanwhile,
information
regarding whether this method can reverse the excessed &-synuclein is still under progress. An important note is that this therapy tends to lower the aggregation of &synuclein
rate,
not
to
degrade
the
effect is equal with the dosage given. The siRNA formula also gave minimal side effect, which was shown by the lack of focal microglial and immunologic reaction – indicating no tissue reaction, the unaffected state of tyrosine hydroxylase and dopamine neurons,
and
also
the
unaffected
neurochemical state (dopamine and its
metabolites). Meanwhile, another study by
high in transfection. One of them is
Lewis et al. (2008) shows that naked siRNA
polyethylene
infused to mice could bring knockdown of
(PEG-PEI). The negativity of siRNA is
&-synuclein protein in hippocampus up to
neutralized by PEI, permit it to easily escape
89% (RT-PCR) and 55% (immunology).
from endosomes, whereas the toxicity of
glycol-polyethyleneimine
cationic PEI is neutralized by PEG. In order The naked siRNA given has low cellular target uptake and high instability. Thus, some
carriers
were
considered.
Some
viruses, such as lentivirus and adenovirus were used. Research by Grobyatuk et al. (2010) shows that shRNA comprised of 19 base
pairs
of
siRNA
embedded
to
adenovirus could decrease level of positive tyrosine
hydroxylase
and
asymmetric
rotational behavior, with efficacy up to 93%. Another study conducted by Cooper et al.
to make the PEG-PEI/siRNA complex, each component in equal volume are diluted with deionized water separately to be mixed gently and incubated in 4-12 hours. The complex could reduce the SNCA gene activity up to 78.64%, 4.36% better than liposome, as studied by Liu et al. (2014). It also
protected
dopamine
neuron
from
apoptosis by 1-methyl-4-phenylpyridinium (MPP+), a positively charged toxic formed by the excess of &-synuclein.
(2014) showed that siRNA carried by modified exosome with rabies virus could
APO!4 Conversion by single-stranded all-
reduce
DNA oligonucleotides
total
&-synuclein
better
than
liposome. The effect reveals in 3 to 7 days
Targeting SNCA alone will result only
with decreasing aggregation forming up to
improvement in motoric function in patient
84%.
But
are
potent
with PD. Another gene therapy for refining
and
highly
cognitive function is also needed even when
potential in biohazard causing reduced
the symptom has not appeared yet. A study
efficacy.
conducted by Nombela et al. (2014) shows
immunogenic,
viral
vectors
mutagenic,
that APO%4 is the most contributed gene in Consequently, the non-viral vectors are
cognitive declining in PD. Thus, silencing
studied for a better delivery of the siRNA.
the APO%4 gene is another approach to treat
Instead of its non-sustained effect of
the disease. Papaioannou et al. (2012) used
delivery, such vector is low in toxicity but
oligonucleotide, which acts to create a minor
mutation in gene targeted, to correct the
later with the oligonucleotides. These
APO%4 overexpression and convert them
enzymes
into APO%3. Oligonucleotide attached to
structure (Picture 5); making the operation
adenovirus as the vector. The single-
of oligonucleotide is more specific and less
stranded adeno-associated virus genome
toxic for another gene.
will
break
the
double-strand
containing Exon 4 of APO%3 and its flanking regions within its ITRs (inverted terminal
repeats),
is
an
effectual
recombination template via a homologous recombination (HR) mechanism (Picture 4).
The study about this method is limited only to atherosclerotic disease. But ssODNs can also applied to the brain because it can be carried either by adenovirus or another nanoparticle vector such as multifunctional
The design suggested is single-stranded all-
envelope-type
DNA oligonucleotides (ssODNs), which the
containing a proton-ionizable amino lipid
sequence is homologues with the gene
(YSK-MEND). APO%3 can also be applied
nearby of the target: those which associated
as the component of PEI-PEG according to
with APO%4 activity. Compared with RNA-
Vinogradov, Poluektova, Makarov, Gerson,
DNA oligonucleotides (RDO), ssODNs is
and Senanayake (2010), make this possible
easily degraded and protected by three
to combine the oligonucleotide with the
phosphorothioate (PTO) bonds at their 5’
siRNA for silencing the SNCA gene. In PD
and 3’ ends. This kind of protection makes
treatment, giving APO%4 targeted therapy is
modified ssODNs is 10-fold greater in
functional both before and when the
correcting genes. However, this protection
cognitive
also
end
Before the symptoms shown, this modality
protection resulted accumulation of cells in
can prevent vascularization impairment and
the G2 phase, which leads to another DNA
later cognitive declining associated. The
damage. This toxicity can be modified again
ssODNs
by internal protection with 4 PTO residues.
production, and delivery ease.
makes
Transcription
ssODNs
with
activator-like
PTO
effector
nucleases (TALENs) are joined with Fok1 – a nonspecific DNA cleavage enzyme and
nano
declining
have
device
symptoms
high
purity,
(MEND)
shown.
simple
Transnasal Route for siRNA and ssODNs
posterior portion of nasal mucosa, allowing
Delivery
the bypass BBB to the brain tissue. The
Since blood-brain barrier (BBB) limits
highly permeable nasal epithelium due to
substance transport into the brain rigorously,
porous endothelial membrane, high total
drug delivery in treatment of PD should be
blood
considered.
modalities
avoidance of first-pass metabolism allow the
chosen: siRNAs and ssODNs in PEG-PEI
rapid absorption of the drug. The drug will
must be delivered to the brain directly, as
track along olfactory and trigeminal nerves,
they are undergone fast breakdown when via
the vasculature, the cerebrospinal fluid, and
oral or fast metabolism via intravenous.
the lymphatic system if drugs inserted
Those methods did not allow the drug to
transnasally.
The
combined
flow,
large
surface
area,
and
reach brain tissue in high concentration. As the result, intratechal route seemed to be good choice in delivering drugs. Instead Querbes et al. (2009) revealed that the route gave the effect within up to 1 week â&#x20AC;&#x201C;faster than
others,
the
route
was
invasive,
especially for the elderly and it was unlikely that siRNAs could be directly delivered to the substantia nigra intratechally in PD pathology.
Study conducted by Born, Lange, Kern, McGregor, Bickel, and Fehm (2002) showed that
transnasal
(MSH/ACTH(4â&#x20AC;&#x201C;10)),
melanocortin(4â&#x20AC;&#x201C;10) vasopressin
and
insulin insertion in human delivered the drugs to cerebrospinal fluid in 30 minutes. Another study by Bleier, Kohman, Feldman, Ramanlal, and Hal (2012) shows high diffusion rate of transnasal high molecular weight (HMW) PEI in mice in 72 hours. The
Other safer routes should be considered for
method also can deliver a wide spectrum of
the drug delivery. Some of them are
therapeutic agents, ranging from small
intranasal and transnasal route. Intransal
molecules to macromolecules, to the CNS.
route allows the drug substances to be
Transnasal route allows the usage of low
absorbed in the entire nose mucosa and
weight molecular (LWM) or high weight
circulate
the
molecular (HWM) PEG-PEI. But HWM PEI
bioavailability will be truncated. Transnasal
is preferable for its higher transfection.
route involves the whole drug container
Since PEG-PEI is hydrophobic, it can be
inserted into nares and touched the most
easily administrated via nasal mucosa. The
in
the
blood;
making
vector also allows the drug within to escape
cognitive
from the endosome in cytoplasm. The
atheroprotective activity.
further research to find effective dosage and
improvement
and
has
3. Modified high molecular weight
minimal proportions of combined siRNA
(HMW)
polyethylene
and ssODNs and PEG-PEI that can cause
polyethyleneimine (PEG-PEI) can
effective outcome should be acquired. One
carry both of the modality with high
thing should be considered is that low
transfection and low toxicity. The
frequency of drug giving is preferable since
drug administered transnasally to
transnasal can cause mucosal damage.
bypass blood-brain barrier so can directly
diffuse
Conclusion
rapidly
and
There are some conclusions regarding the
bioavailability.
topic based on discussion above:
in
glycol-
brain
with
tissue highly
4. There should be an in vitro and in
1. There are no effective curative
vivo study regarding the design of
efforts for Parkinson Disease. Some
the drugs to prove our hypotheses
drugs like levodopa or dopamine
that this model can improve motoric
agonists create some adverse effects
and
and tolerance of the drugs is also
Parkinson’s disease patients. The
occurred.
treatments
further research to find effective
available are highly invasive with
dosage and frequency of drug giving
loads of complications.
should also be acquired. With this
Surgical
2. siRNA for SNCA genes resulting in lowered
the
gene
activity
and
cognitive
impairment
of
review we hope that we as medical students have a wide knowledge
causing inhibition of &-synuclein
about
aggregation, which delays and repair
Parkinson’s disease treatment and
motoric impairment in people with
aroused to conduct such a research
Parkinson’s
regarding the model we offered.
disease.
Meanwhile,
APO%4 conversion to APO%3 with single-stranded
all-DNA
oligonucleotides (ssODNs) causes
molecular
aspects
of
to the human brain.Nature neuroscience, 5(6), 514-516. 6. Braak, H., Tredici, K. D., RĂźb, U.,
References 1. Aarsland, D., & Kurz, M. W. (2010). The
epidemiology
associated
of
with
dementia Parkinson
de Vos, R. A., Jansen Steur, E. N., & Braak, E. (2003). Staging of brain pathology
related
to
sporadic
disease. Journal of the neurological
Parkinsonâ&#x20AC;&#x2122;s disease.Neurobiology of
sciences, 289(1), 18-22.
aging, 24(2), 197-211.
2. Alafuzoff,
I.,
&
(2014).
Staged
Parkkinen,
L.
pathology
in
7. Brichta,
L.,
Greengard,
pharmacological
related disorders, 20, S57-S61.
Parkinson's
Baboota, S., Kohli, K., Ali, J., ... & Akbar, M. (2010). Strategy for
&
Flajolet, M. (2013). Advances in the
Parkinson's disease.Parkinsonism & 3. Alam, M. I., Beg, S., Samad, A.,
P.,
treatment
disease:
of
targeting
neurotransmitter systems. Trends in neurosciences, 36(9), 543-554. 8. Cooper, J. M., Wiklander, P. B.,
effective brain drug
Nordin, J. Z., Al!Shawi, R., Wood,
delivery. European Journal of
M. J., Vithlani, M., ... & Alvarez!
Pharmaceutical Sciences, 40(5),
Erviti, L. (2014). Systemic exosomal
385-403.
siRNA delivery reduced alpha!
4. Bleier, B. S., Kohman, R. E.,
synuclein aggregates in brains of
Feldman, R. E., Ramanlal, S., &
transgenic mice. Movement
Han, X. (2013). Permeabilization of
Disorders, 29(12), 1476-1485.
the blood-brain barrier via mucosal
9. Dhuria, S. V., Hanson, L. R., & Frey,
engrafting: implications for drug
W. H. (2010). Intranasal delivery to
delivery to the brain. PloS one, 8(4),
the central nervous system:
e61694.
mechanisms and experimental
5. Born, J., Lange, T., Kern, W.,
considerations. Journal of
McGregor, G. P., Bickel, U., &
pharmaceutical sciences, 99(4),
Fehm, H. L. (2002). Sniffing
1654-1673.
neuropeptides: a transnasal approach
10. Gorbatyuk, O. S., Li, S., Nash, K., Gorbatyuk, M., Lewin, A. S.,
Sullivan, L. F., ... & Muzyczka, N.
... & Bohn, M. C. (2011). An alpha-
(2010). In vivo RNAi-mediated &-
synuclein AAV gene silencing vector
synuclein silencing induces
ameliorates a behavioral deficit in a
nigrostriatal degeneration. Molecular
rat model of Parkinson's disease, but
Therapy, 18(8), 1450-1457.
displays toxicity in dopamine
11. Honey, C. R., & Palur, R. S. (2001).
neurons. Brain research, 1395, 94-
Surgery for Parkinson's
107. doi:
disease. BRITISH COLUMBIA
doi:10.1016/j.brainres.2011.04.036.
MEDICAL JOURNAL, 43(4), 210213.
16. Lewis, J., Melrose, H., Bumcrot, D., Hope, A., Zehr, C., Lincoln, S., ... &
12. Jankovic, J., & Aguilar, L. G.
Farrer, M. J. (2008). In vivo
(2008). Current approaches to the
silencing of alpha-synuclein using
treatment of Parkinson’s
naked siRNA.Molecular
disease. Neuropsychiatric disease
neurodegeneration, 3(1), 1-10.
and treatment, 4(4), 743.
17. Liang, Y., Liu, Z., Shuai, X., Wang,
13. Jankovic, J. (2008). Parkinson’s disease:
clinical
diagnosis.Journal
features of
and
Neurology,
W., Liu, J., Bi, W., ... & Tao, E. (2012). Delivery of cationic polymer-siRNA nanoparticles for
Neurosurgery & Psychiatry, 79(4),
gene therapies in neural
368-376.
regeneration. Biochemical and
14. Khodr, C. E., Becerra, A., Han, Y.,
biophysical research
& Bohn, M. C. (2014). Targeting
communications, 421(4), 690-695.
alpha-synuclein with a microRNA-
doi:
embedded silencing vector in the rat
http://dx.doi.org/10.1016/j.bbrc.2012
substantia nigra: Positive and
.03.155.
negative effects. Brain
18. Liu, Y., Liu, Z., Wang, Y., Liang, Y.
research, 1550, 47-60. doi:
R., Wen, X., Hu, J., ... & Cheng, D.
http://dx.doi.org/10.1016/j.brainres.2
(2013). Investigation of the
014.01.010.
performance of PEG–PEI/ROCK-II-
15. Khodr, C. E., Sapru, M. K., Pedapati, J., Han, Y., West, N. C., Kells, A. P.,
siRNA complexes for Alzheimer's disease in vitro. Brain
research, 1490, 43-51. doi:
Disease. Journal of Movement
http://dx.doi.org/10.1016/j.brainres.2
Disorders, 4(1), 1.
012.10.039.
23. McCormack, A. L., Mak, S. K.,
19. Liu, Y. Y., Yang, X. Y., Li, Z., Liu,
Henderson, J. M., Bumcrot, D.,
Z. L., Cheng, D., Wang, Y., ... &
Farrer, M. J., & Di Monte, D. A.
Wang, H. J. (2014). Characterization
(2010). &-synuclein suppression by
of Polyethylene Glycol!
targeted small interfering RNA in the
Polyethyleneimine as a Vector for
primate substantia nigra. PLoS
Alpha!Synuclein siRNA Delivery to
One, 5(8), e12122. 24. Mercury, M. G., Tschan, W., Kehoe,
PC12 Cells for Parkinson's Disease. CNS neuroscience &
R., & Kuechler, A. (2007). The
therapeutics, 20(1), 76-85. doi:
presence of depression and anxiety
10.1111/cns.12176.
in Parkinson's disease. Disease-a-
20. Luk, K. C., & Lee, V. M. Y. (2014). Modeling
month, 53(5), 296-301.
Lewy
pathology
25. Mosley, R. L., Hutter-Saunders, J.
in
Parkinson's
A., Stone, D. K., & Gendelman, H.
&
E.
propagation
disease. Parkinsonism
related
disorders, 20, S85-S87. 21. Malhotra, M., Tomaro-Duchesneau,
(2012).
and
adaptive immunity in Parkinsonâ&#x20AC;&#x2122;s disease. Cold
C., & Prakash, S. (2013). Synthesis
perspectives
of TAT peptide-tagged PEGylated
a009381.
chitosan nanoparticles for siRNA
Inflammation Spring in
Harbor
medicine, 2(1),
26. Muangpaisan, W., Hori, H., &
delivery targeting neurodegenerative
Brayne,
diseases. Biomaterials, 34(4), 1270-
review
1280. doi:
incidence of Parkinson's disease in
http://dx.doi.org/10.1016/j.biomateri
Asia. Journal
als.2012.10.013.
epidemiology, 19(6), 281-293.
22. Maraganore, D. M. (2011). Rationale
C. of
(2009). the
Systematic
prevalence
and of
27. Nombela, C., Rowe, J. B., Winder-
for Therapeutic Silencing of Alpha-
Rhodes, S. E., Hampshire, A., Owen,
Synuclein in Parkinsonâ&#x20AC;&#x2122;s
A. M., Breen, D. P., ... & Barker, R. A. (2014). Genetic impact on
cognition and brain function in
delivery of siRNA mediates robust
newly diagnosed Parkinson’s
silencing in
disease: ICICLE-PD study. Brain, 1-
oligodendrocytes. Oligonucleotides,
16. doi: 10.1093/brain/awu201.
19(1), 23-30.
28. Noviani, E., Gunarto, U., & Setyono, J.
(2010).
Hubungan
Antara
33. Rao, D. D., Vorhies, J. S., Senzer, N., & Nemunaitis, J. (2009). siRNA
Merokok dengan Penyakit Parkinson
vs. shRNA: similarities and
Di
differences. Advanced drug delivery
RSUD
Prof.
Dr.
Margono
Soekarjo Purwokerto. Mandala of Health. 4(2).
reviews, 61(9), 746-759. 34. Samuel, M., Maidment, I., Boustani,
29. Okun, M. S. (2014). Deep-Brain
M., & Fox, C. (2006). Clinical
Stimulation—Entering the Era of
management of Parkinson’s disease
Human
dementia: pitfalls and
Neural-Network
Modulation. New England Journal of
progress. Advances in Psychiatric
Medicine, 371(15), 1369-1373.
Treatment, 12(2), 121-129.
30. Parkinson Study Group. (2000).
35. Schapira, A. H. V. (2005). Present
Pramipexole vs levodopa as initial
and future drug treatment for
treatment for Parkinson disease: a
Parkinson’s disease. Journal of
randomized
Neurology, Neurosurgery &
controlled
trial. Jama, 284(15), 1931-1938. 31. Papaioannou, I., Simons, J. P., &
Psychiatry, 76(11), 1472-1478. 36. Tamaru, M., Akita, H., Nakatani, T.,
Owen, J. S. (2012). Targeted in situ
Kajimoto, K., Sato, Y., Hatakeyama,
gene correction of dysfunctional
H., & Harashima, H. (2014).
APO# alleles to produce
Application of apolipoprotein E-
atheroprotective plasma APO%3
modified liposomal nanoparticles as
protein. Cardiology Research and
a carrier for delivering DNA and
Practice, 2012, 1-16. doi:
nucleic acid in the
10.1155/2012/148796.
brain.International journal of
32. Querbes, W., Ge, P., Zhang, W., Fan,
nanomedicine, 9, 4267. doi:
Y., Costigan, J., Charisse, K., ... &
http://dx.doi.org/10.2147/IJN.S6540
Sah, D. W. (2009). Direct CNS
2.
37. Tan, L. C. S. (2013). Epidemiology
NRTIs: efficient inhibitors of HIV
of Parkinsonâ&#x20AC;&#x2122;s Disease. Neurology
type-1 in macrophages with a
Asia. 18(3):231-238.
reduced mitochondrial
38. Thomas, B., & Beal, M. F. (2007). Parkinsonâ&#x20AC;&#x2122;s
Disease.
Human
Molecular
Genetics.
16(2).
doi:10.1093/hmg/ddm159. 39. Tsuang, D., Leverenz, J. B., Lopez, O. L., Hamilton, R. L., Bennett, D. A., Schneider, J. A., ... & Zabetian, C. P. (2013). APO$ '4 Increases Risk
for
Dementia
in
Pure
Synucleinopathies. JAMA neurology, 70(2), 223-228. 40. Vinogradov, S. V., Poluektova, L. Y., Makarov, E., Gerson, T., & Senanayake, M. T. (2010). Nano-
toxicity. Antiviral chemistry & chemotherapy,21(1).
Tables and figures
Figure 1. Pharmacologic treatment options available for PD. Jankovic & Aguilar, 2008.
Figure 2. Outcome of &-synuclein siRNA exposure on level of &-synuclein after unilaterally infused into the left hemisphere. Midbrain sections immunostained with anti-&-synuclein, revealed more robust &-synuclein immunoreactivity of untreated (A) vs. siRNA-infused (B) substantia nigra. Scale = 5 (m. (C) Optical density measurements of nigral &-synuclein immunoreactivity showing &-synuclein portion compared to right (untreated) substantia nigra. *p<0.03.
Figure 3. Cytotoxicity of PEG-PEI/siSNCA in PC12 cells assessed via MTT assay at 48 h posttransfection and represented as percentage of viable cells relatively to untreated control cells (Left). PEG-PEI/siSNCA effectiveness in suppressing SNCA gene expression in PC12 cells evaluated by western blot analysis (Right). ***P < 0.001 versus control.
Figure 4. Conversion of the mutant APO#2 allele to wild-type APO#3 using an AAV-based DNA repair sequence with single-stranded adenovirus with Exon 4 of APO#3 and its flanking regions inside its ITRs (inverted terminal repeats). The same method applied in APO#4 allele.
Figure 5. Double-strand breaks (DSBs) arouse homologous recombination (HR) repair by facilitating exchange of DNA sequence between donor and acceptor molecules, with recombination of similar sequences.
Figure 6. Various pathways for reaching the brain after intranasal administration
Table 1 Designation of siRNA in SNCA Gene Silencing Study
Base Pair Included
Delivery Method
Lewis et al. (2008)
AACAGTGGCTGAGAAGACCAA
Naked
McCormack (2010)
cuAuGAAcccGAAGccuAATsT
Naked
Cooper et al. (2014)
GACAAAUGUUGGAGGAGCAdTdT RBV-Exosome
LITERATURE REVIEW Farnesyl Transferase Inhibitor (FTI): a Potential Novel Drug of Longevity in Vascular Aging Christopher Adhisasmita Yandoyo1, King Panji Islami1, Raita Faza Amalia1 1
Faculty of Medicine, Trisakti University (AMSA-Usakti) Abstract
Hutchinson-Gilford Progeria Syndrome is a rare premature aging syndrome that affect children resulting destructive effect in cellular metabolism. Progeria patient usually die due to heart attack and stroke caused by vascular stiffness resulted of accumulation of progerin. Scientist found that premature vascular syndrome caused by accumulation of progerin has the same mechanism in normal aging people and we conducted a study of possibility of Farnesyl Transferase Inhibitor (FTI) as potential drug of preventing this mechanism in aged patient. This study is conducted by literature review from trusted and updated journals and websites associated to the pathologic basis of the disease, current management of the disease, and the underlying reasons and evidences of possibilities using FTI as a potential drug for preventing vascular aging in aged patients. We analyzed the data and information by giving the argument through logical thinking and were then taken to a conclusion. The use of FTI in reversing the mechanism of aging in progeria patient has shown many promising results as many patients in clinical trial shown an improvement not only in vascular stiffness but also in bone structure and audiological status. In mice model of progeria, the treatment of FTI also shown the improvement even the possibility of reversible mechanism damage caused by progerin even reducing the production of atherosclerosis in APO E deficient mice model. For many years scientist has studied about aging and they finally found breathtaking major factor of aging especially in vascular aging in a very rare genetic premature aging phenomenon called progeria. This theory is also related to the shortening of telomere in every human so that it shows promising evidence and possibilities of preventing aging especially vascular aging in every human by using FTI drug as their major arsenal. Keywords: Progeria, Progerin, Telomere, Vascular aging, Farnesyl Transferase Inhibitor (FTI)
Introduction
prelamin A protein, referred to as progerin. (Ragnauth, et. al., 2010) (McClintock, et. al.,
Hutchinson-Gilford
Progeria
Syndrome
2006)
("Progeria", or "HGPS") is a rare (1 in 4 million),
fatal
genetic
condition
of
segmental premature aging syndrome caused by defects in the integrity of the nuclear
Fig 1. Normal Prelamin A Processing and alteration in Hutchinson-Gilford Progeria Syndrome
lamina. It is called a segmental premature aging syndrome because it does not mimic aging completely. Its name is derived from the Greek and means "prematurely old." While there are different forms of Progeria including Werner's syndrome, also known as "adult progeria" which does not have an onset until the late teen years, with a life span into the 40's and 50's. Death occurs at a mean age of 13 years, usually from heart attack or stroke. In Indonesia, one of many resources have mentioned one patient with HGPS who passed away while she was 11 in 2006 (Olive, et. al., 2010) (Indriana, et. al., 2006)
The study of many researchers recently provides insights about the interaction between this toxic protein (progerin) and telomeres. The researchers have found that short or dysfunctional telomeres activate production of progerin, which is associated with age-related cell damage. As the telomeres
shorten
mainly
because
of
oxidative stress as we are aging, the cell produces more progerin, the toxic protein, even when they do not carry the mutation. The more cell divisions the cell underwent, the shorter the telomeres and the greater the production of progerin. (Cao, et. al., 2011) (Trigueros-Motos, et. al., 2011)
HGPS is caused by a mutation in the gene called LMNA (pronounced, lamin - a). The
The relationship between progeria and
LMNA gene produces the Lamin A protein,
normal aging especially in cardiovascular
intermediate filament proteins that provide
aging has brought new hope to the aged
the structural scaffold for the nuclear
people as there is currently no specific
lamina. In the majority of cases, a specific
therapy for preventing our cardiovascular
mutation (G608G) activates a cryptic splice
system especially our blood vessel from
site, resulting in the generation of a mutant
aging, and preventive therapy for preventing
cardiac and vascular disease such as
vascular
calcification
lowering the blood pressure, lowering the
association. In this finding, 137 mummies
level of blood glucose and cholesterol are
up to 4000 years old were examined with
the only treatment for preventing the
computed
incidence of cardiovascular disease. (Fuster,
calcification was present in 47 of 137 or
et. al., 2011)
34% of the mummies, and age at the time of
tomography
is
an
scans.
age-old
Vascular
death correlated positively with the presence To understand the cellular and molecular mechanisms
that
underlie
aging-related
vascular calcification, investigators have begun
to
focus
on
the
vascular
pathophenotype associated with HutchinsonGilford progeria syndrome (HGPS). The disease
is
characterized
in
part
by
accelerated aging with early atherosclerosis and vascular calcification. Nevertheless, the causative
mechanisms
for
precocious
vascular calcification in this disease have not been elucidated fully.
consequence of aging, is recognized to be a highly regulated process skin to bone Vascular
vascular beds with calcified vessels. In the modern era, the incidence of vascular calcification has been shown to increase with advancing age and has been reported to be <5% annually for individuals <50 years of age to >12% for individuals >80 years of age. When present, vascular calcification portends a worse clinical outcome; a metaanalysis of 218 000 patients found a 3.94fold higher risk for cardiovascular mortality and a 3.41-fold higher risk for any
Vascular calcification, considered a passive
formation.
of vascular calcification and the number of
calcification
is
prevalent to ethnicities and age groups, and observational studies prove an interaction
cardiovascular event. Then, understanding how aging influences the pathobiology of vascular calcification may have far-reaching implications for associated cardiovascular morbidity and mortality. (Leopold, J. A., et. al. 2013)
between aging in asymptomatic adults and
Farnesyltransferase inhibitors (FTIs) are
in individuals with established coronary
potent and selective inhibitors of
artery disease.
intracellular which reversibly bind to the
Updated findings from the HORUS study have shown that the link between aging and
farnesyltransferase (FTase) CAAX binding site, thereby inhibiting progerin
farnesylation and intercalation into the
using noncompartmental analyses and the
nuclear membrane. (Gordon, et al., 2012).
Pharmacodynamics was assayed in lysates
More than a decade later, at least six FTIs are being, or have been, tested in clinical trials, including BMS-214662, L778123, tipifarnib (Zarnestraâ&#x201E;˘), lonafarnib (Sarasar), FTI-277 and L744832. (Appels,et al., 2005) .
from peripheral blood mononuclear cells pretherapy, at 52 wk on lonafarnib, and at end of therapy. Western blotting for HDJ-2 gel mobility shifts was performed as previously reported (Adjei AA, et al. 2000). Western blots were quantified using a Molecular
Imager
Gel
Dock
XR
In August 2005 and February 2006,
densitometer (Bio-Rad). Data were analyzed
researchers published studies that support a
using Quantity One software (Bio-Rad) of
potential drug treatment for children with
FTI activity.
Progeria. Farnesyltransferase inhibitors
Cardiovascular
Testing
Details.
(FTIs), originally developed for cancer, are
Fasting carotid-femoral pulse wave velocity
capable of reversing the dramatic nuclear
(PWVcf) (Oâ&#x20AC;&#x2122;Rourke, et. al., 2002). PWVcf
structure abnormalities that are the hallmark
was calculated using the formula PWVcf =
of cells from children with Progeria, include
lcf/)tcf. Fasting diagnostic carotid artery
the Cardiovascular issues. (progeria
ultrasonography
research, 2014)
established
Method
was
protocols
performed (De
using Sandre-
Giovannoli A, et al. 2003). Carotid stenoses were graded using velocity ratios, and
This scientific paper is based on literature
pulsedwave Doppler was performed with
review with specialty in medicine which
appropriate angle correction. (Eriksson M, et
discuss about the effectivity and the
al. (2003).
effectivity and the efficacy of using FTase
All of the data collected from the
inhibitor (FTI) as a novel drug for longevity
recently updated journals and many trusted
of cardiovascular aging.
websites were compiled based on the
The researcher was Measuring the
suitability in this paper then elaborated it
Pharmacokinetic of FTI by using by
using any of fact given in the data and then
HPLC/ion chromatography (IC) tandem
analyzed the data and information by giving
mass spectrometry and were determined
the argument through logical thinking to
seek and found any correlation between any
and
of those data and were then taken to a
lonafarnib treatment (Table. 1) (Gordon, et
conclusion.
al. 2012)
Result
deep
adventitia
decreased
with
Figure 3. Echodensity improvement with
Increase of celullar sensitivity in vascular
Lonafarnib (type of FTI) therapy.
cells could contribute to loss of smooth muscle cells and the development of
The other research, in mice, indicate that the
arteriosclerosis (Verstraeten, et al. 2008)
inhibition of farnesyltransferase prevents accumulation of lipid-laden macrophages and
Research
found
there
was
any
proliferation
and
migration
of
smooth
cardiovascular changes before and after
muscle-like cells in the vascular intima.
FTIs theraphy in Progeria patients. At
(Sugita, et al. 2007)
pretherapy, the carotid-femoral pulse wave velocity (PWVcf) in 18 subjects was 3.5 times greater than the established pediatric normal values, indicating high arterial stiffness and low distensibility (median: 12.9 m/s; range: 7.2â&#x20AC;&#x201C;18.8 m/s). At end of treatment, PWVcfdecreased by a median of 35%
(range:
increase, P = observed
48%
decrease
0.0001)
with
change
in
to a
26%
median
PWVcf (post-
The fact that FTIs improved nuclear shape and repair the skin cell and vascular issues also in HGPS cells raised hope for a potential therapy and stimulated interest in testing the efficacy of FTIs. (Capell et. al., 2008) Figure 3. The improvement of progeria skin cell treated with FTI
vs.
pretreatment) of *4.5 m/s (range: *7.4m/s to 1.9 m/s). Carotid arteries demonstrated greater wall echodensity at the intima media and near adventitia in HGPS patients.
Discussion Progerin and Normal Aging
Echodensity of the intima media and near The correlation of progeria and ging has
breakthrough in the field of medicine but
been a major concern among scientist in this
also offer researchers a rare opportunity to
past few years. Finding the correlation
observe in just a few years what
between them is not only giving a new
Would
otherwise
require
decades
of
longitudinal studies.
ribbon of DNA; rather, the cell splices together segments of genetic information called exons that contain the code for
In 2003, NHGRI researchers discovered that
building
proteins,
a mutation in LMNA causes the rare
intervening
premature aging condition caused by the
information called introns. This mechanism
protein produced by this gene, Progerin.
appears to be altered by telomere shortening,
Progerin is a mutated version of a normal
and affects protein production for multiple
cellular protein called lamin A, which is
proteins that are important for cytoskeleton
encoded by the normal LMNA gene. Lamin
integrity. Most importantly, this alteration in
A helps to maintain the normal structure of a
RNA splicing affects the processing of the
cellâ&#x20AC;&#x2122;s nucleus, the cellular repository of
LMNA messenger RNA, leading to an
genetic information.(Eriksson, et. al., 2003)
accumulation of the toxic progerin protein.
letters
and of
removes unused
the
genetic
(NIH, 2011) In a 2007 study, NIH researchers showed that normal cells of healthy people can
Telomerase is an enzyme that can extend the
produce a small amount of progerin, the
structure of telomeres so that cells continue
toxic protein, even when they do not carry
to maintain the ability to divide. One study
the mutation. The more cell divisions the
show the telomere-progerin link, showing
cell underwent, the shorter the telomeres and
that cells that have a perpetual supply of
the greater the production of progerin.
telomerase, known as immortalized cells, produce very little progerin RNA. Most cells
The research suggests that the shortening of telomeres during normal cell division in individuals with normal LMNA genes somehow alters the way a normal cell
of this kind are cancer cells, which do not reach a normal cell cycle end point, and instead replicate out of control. (Masood, et. al., 2011)
processes genetic information when turning it into a protein, a process called RNA
Other
splicing.
is
laboratory tests on normal cells from healthy
instructions
individuals using biochemical markers to
transcribed
To
build from
proteins, genetic
RNA
the
the
researchers
occurrence
also
of
conducted
embedded in DNA. RNA does not carry all
indicate
progerin-
of the linear information embedded in the
generating RNA splicing in cells. The cell
donors ranged in age from 10 to 92 years.
progerin) retains the farnesyl group. Indeed,
Regardless of age, cells that passed through
the initial step in causing the disease is the
many cell cycles had progressively higher
failure to remove the farnesyl group. This
progerin production. Normal cells that
failure
produce higher concentrations of progerin
mutation results in deletion of the part of
also displayed shortened and dysfunctional
prelamin a needed for FACE 1 to bind and
telomeres, the tell-tale indication of many
remove the farnesyl group. Thus, the cause
cell divisions.
of the defects in aging and Progeria are the
happens
because
the
Progeria
same: FACE1 cannot do its job. (Ragnauth, Figure 2. 93 year-old personâ&#x20AC;&#x2122;s skin without
progeria
showing
amount of cells containing progerin. Progeria
and
its
relationship
Telomere shortening and vascular disease with
Vascular Aging
University have made a major advance in elucidating a key step in the aging of human especially in blood vessels (vascular aging.) Group's two key findings are: (1) prelamin A accumulates in vascular smooth muscle cells (VSMCs) of aged individuals but not young
individuals, and
(2)
this
accumulation results, at least in part, from depletion of the enzyme FACE1. FACE1 (also called Zmpte24) is required for the removal of the farnesyl group in prelamin A, during processing to normal lamin A, a critical component of the cell nucleus. This situation Progeria.
is
very
There,
A number of clinical cross-sectional case control and longitudinal cohort studies have
Catherine Shanahan and her group at Oxford
of
et. al., 2010)
massive
similar prelamin
to
that a
in
(called
shown that it has related an increased incidence
of
coronary
artery
or
atherosclerotic disease to shortened telomere length in peripheral blood leukocytes. It considers leukocyte telomere length was found to decrease by 6% to 9% per decade, and several of its studies noted the robust predictive value of shortened telomere length for future cardiovascular events, including the observation that the predictive power of this index appears to persist even after
controlling
inflammatory,
for and
standard
clinical,
echocardiographic
markers of risk. (Fuster, et. al., 2011)
Similarities pathology
between
HGPS
and
vascular
exhibit calcification, inflammation, and
conventional
evidence of plaque erosion and/or rupture.
atherosclerosis of aging
Although HGPS lesions tended to have smaller atheromatous cores relative to more
Relatively little is known regarding the cardiovascular pathology of HGPS. While there
are
cardiac
and
vascular
commonalities between HGPS and aging, such as severe vessel blockage, there is also a lack of classical risk factors in HGPS such as
hypercholesterolemia
serum
hs-CRP,18
in
and
increased
early
stage
hypertension, and smoking. Isolated from these risk factors, the study of HGPS may provide an opportunity to discover new elements that influence the vascular disease of aging. Reports to date have not examined genetically confirmed HGPS and therefore are difficult to interpret. Here we describe the cardiovascular pathology in two children with the de novo heterozygous mutation 1824C>T in LMNA and typical HGPS disease course, who lack CVD risk factors established for the general population. In the face of this, we found global atherosclerosis and a pathologic profile that overlaps significantly with classic atherosclerosis of aging. Similar to geriatric CVD, we found a spectrum of early to late-stage plaques in the HGPS patient samples. Arterial lesions in both typical atherosclerosis and HGPS
typical
atherosclerosis,
attributable
to
this
the
may lack
be of
hypercholesterolemia and dyslipidemia in the HGPS patients. In our study, the composition of the HGPS lesions indicates that the ECM is similar to adult CVD consistent with progressive atherosclerotic lesion
development
and
an
in
situ
inflammatory process. Most likely, multiple cell types are involved in the HGPS vascular pathology. Macrophages may have a role as well as VSMC with their limited capacity for cell renewal. In contrast to typical adult CVD however, we identified markedly thickened adventitia in large, medium and small arteries, and in veins. This is a new finding, not noted in previous reports of progeria cases. It would be anticipated that such profound fibrosis would lead to diminished vascular compliance, increased vessel stiffness and potential predisposition to formation of intimal plaque. In HGPS, progerin accumulation may be a major factor that underlies the development of these premature vascular lesions.
The adventitia is rapidly gaining recognition
and subsequently damages the intima,
as an active participant in the development
heralding plaque formation.
of atherosclerosis and vascular response to injuries. Aortic stiffness can contribute to
In our aging cohort, progerin-positive
increased afterload and development of left
vascular cells were largely SMA negative.
ventricular
that
Although we did not attempt to further
observed in patient HG001. Progressive
analyze their specific identity, their general
vascular stiffness occurs in geriatric patients
shape was fibroblastoid. Some cells may be
and is considered a major predictor of
adventitial fibroblasts, or perhaps immune
adverse coronary events, though it is
cells such as macrophages or other cell types
typically accompanied by a much milder
that accumulate in response to resident cell
degree of adventitial fibrosis.
death.
hypertrophy,
such
as
Cells
within
the
media
could
potentially be inflammatory cells as well, or We also identify a new component in the
SMA negative dedifferentiated VSMCs
typical aging process by demonstrating that
commonly found in atherosclerotic lesions.
progerin is present in the coronary arteries
Future study to identify the progerin-
of
and
positive cell types in aging vessels would
increases with advancing age. Thus, resident
help to elucidate what roles they play in the
vascular cells infrequently use the cryptic
development of atherosclerosis.
non-HGPS
aging
individuals,
splice site in exon 11 of LMNA in vivo. Interestingly, in normal fibroblast lines,
Though the rodent model shows prominent
progerin-positive
mitotic
SMC dropout from the media of older
defects that increase with passage number.7,
HGPS arteries, medial SMC dropout is not a
8 This observation supports a correlation
prominent feature in our human study. In
between
mitotic
our study, we cannot distinguish the mild
abnormalities and normal aging. The highest
medial cell dropout in HGPS from the
number of progerin positive cells in non-
typical secondary effects of atherosclerosis.
HGPS arteries was in the adventitia,
The reasons for the murine and human
introducing the possibility that some vessel
differences are unclear but it should be
insult is initiated in this deep vessel layer,
noted that even in the mouse model, SMC
cells
progerin
exhibit
induced
dropout is highly variable within the
vascular tree and some areas did not display
speculate that progerin accumulation in
loss (F. Collins, personal communication).
vascular cells causes nuclear defects and
Thus, the available sampling from the HGPS
increased susceptibility to mechanical strain
human cases may not have encompassed the
that in turn triggers some combination of
same areas of the aorta that showed severe
cell death, and inflammatory response,
drop-out in mice. Of note, a prior human
resulting in atherosclerosis. Since oxidative
autopsy (though not definitively HGPS due
stress-induced free radicals have been
to lack of genetic analysis), noted unusual
implicated in vitro in the pathology of
aortic medial SMC depletion, the extent of
HGPS, a systematic quantitative comparison
which varied from site to site. Alternatively,
of lipid peroxidation products in HGPS and
medial cell death may not influence human
geriatric samples is warranted. Finally,
vascular pathogenesis as strongly in the
because over expression of farnesylated
human as in the HGPS mouse model.
prelamin A has been implicated in progeroid
Additional work, beyond the scope of the
damage,
current study, would be valuable in further
examination of prelamin A expression in
elucidating a pathologic association between
HGPS and in aging vessels could further
progerin expression and the development of
identify key roles for altered lamin A
atherosclerosis in both HGPS and the
proteins
general population. For example, does the
Atherosclerosis is a consequence of arterial
comparatively
steadily
wall healing in response to injury. In most
increasingâ&#x20AC;&#x201C;level of progerin influence age-
individuals, this is a multifactorial process
related atherosclerosis by inducing a low-
with contributions from a host of known risk
level smoldering chronic injury? This might
factors
explain
hypercholesterolemia, etc.), but with a
the
smallâ&#x20AC;&#x201D;but
differences
in
adventitial
a
systematic
in
these
populations.
(e.g., component
pathological
hypertension,
pathology between HGPS, where progerin is
significant
of
unidentified
extensive, and aging, where progerin is low
contributing factors. This study supports the
but persistently increasing. The question
possibility that progerin is a contributor to
could be addressed by study of progerin
risk of atherosclerosis in the general
expression in a larger cohort of non-HGPS
population. The current observations arise
individuals with well-defined cardiovascular
from a small scale survey; however the
medical history (low vs high CVD risk). We
presence of progerin in aging vasculature
merits examination as a potential new
required
for
removal
of
its
post-
element influencing vascular health with
translationally attached farnesyl moiety.
aging. (Olive, et. al., 2010).
Progerin is proven to remain associated with the inner nuclear membrane, unable to be
The
Potential
effect
of
Farnesyl
Transferase Inhibitor (FTI) in vascular
released for degradation due to persistent farnesylation.
aging The farnesylation of progerin targets the protein to the nuclear envelope, where it might weaken the nuclear lamina and cause nuclear stiffness. Blocking farnesylation with an FTase inhibitor (FTI) would dislocated progerin away from the nuclear envelope and reduce nuclear stiffness. Recovering the nuclear stiffness may repair the vascular damage. Damage of nuclear integrity
results
in
increased
cellular
sensitivity. (Yang, et al., 2005)
FTI reduced the number of nuclear stiffness in fibroblasts from mice with a targeted HGPS mutation. FTIs also improved nuclear shape in fibroblasts from humans with HGPS.
Treating
fibroblasts
with
FTI
restored nuclear stiffness in HGPS cells and accelerated the wound healing response in HGPS
and
increasing
healthy directional
control
cells
by
persistence
of
migrating cells but did not improve cellular sensitivity to mechanical strain. Increased
Studies found that Progerin had higher
biomechanical sensitivity might provide a
concentration in skin and the vascular wall
potential mechanism for the loss of vascular
of normal older people compared to
smooth muscle cells progressively.(Yang, et.
younger, suggesting a role in normal aging.
al., 2010) (Verstraeten, et. al., 2008)
Progerin lacks the proteolytic cleavage site
1. Hutchinson-Gilford
Conclusion
Progeria
(Progerin). Progerin causing many of
Syndrome ("Progeria", or "HGPS")
cellular instability and weakness
is a deteriorating rare, fatal genetic
resulting of segmental premature
condition caused by accumulation of
aging syndrome in the patient. One
mutated
of the major cause of death for the
LMNA
gene
product
patient with progeria syndrome is the
combination of farnesyl group and
presentation of cardiovascular or
pre lamin A protein (progerin) and
cerebrovascular disease in a very
producing mature of LMNA gene
young age at a mean age of 13 years.
product, Lamin A which essential for
2. Scientist has found that this protein,
keeping the cellular also vascular
progerin is actively produced by the
instability
progeria patient due to the genetic
aging in overall. Recent study has
mutation of the disease and produced
found that FTI could be a potential
by the normal aging person as the
treatment for children with progeria
result of the shortening of our
by reducing the amount of progerin
telomere.
protein and be a potential drug for
Progerin
is
actively
to
prevent
causing cellular stiffness, vascular
decreasing
stiffness, and vascular instability and
vascular stiffness and may be other
aging both in HGPS and in normal
senescence
aging
aging people despite the shortening
patient.
This
breathtaking
discovery has brought many scientist to study both the mechanism of vascular aging in progeria patient and in the normal aging and in recent
the
premature
possibilities
syndrome
in
of
normal
of our telomere during aging. References 1. Adjei AA, et al. (2000) A Phase I
the
trial of the farnesyl transferase
similarity of the mechanism of
inhibitor SCH66336: Evidence for
vascular
biological
years,
study
has
stiffness
revealed and
vascular
instability in both progeria and normal aging people. 3. Farnesyl Transferase Inhibitor (FTI) is one type of drug using for treating cancer. It mechanism is basically preventing the farnesyl group for attaching the pre lamin A protein produced by LMNA gene thus preventing its destructive effect of
and
clinical
activity.
Cancer Res 60:1871â&#x20AC;&#x201C;1877. 2. Appelsa, N. M. G. M., Beijnena, J. H., Schellens, Development
J.
H. of
M.
(2005) Farnesyl
Transferase Inhibitors: A Review. 10 (8).
565-578.
doi:
10.1634/theoncologist.10-8-565 3. Cao, K., Blair, C. D., Faddah, D. A., Kieckhaefer, J. E., Olive, M., Erdos,
M. R.,......., Collins, F. S. (2011).
8. FTIs - a potential drug treatment for
Progerin and telomere dysfunction
children
collaborate
cellular
Retrieved
human
http://progeriaresearch.org/the_fti_dr
senescence
to in
trigger normal
fibroblasts. J Clin Invest. 121(7), 2833-2844./ doi: 10.1172/JCI43578 4. Capell, B. C., Olive, M., Erdos, M.
with
Progeria.
(2014). from
ug.html 9. Fuster, V., Hachinski, V., Kovacic, J.C., Moreno, P., Nabel. E. G.
R., Cao, K., Faddah, D., Tavarez, U.
(2011),
L.,……, Collins, F. S. (2008). A
Vascular Disease, and Aging: Part 1
farnesyltransferase inhibitor prevents
of a 2-Part Review. Circulation, 123,
both the onset and late progression of
1650-1660/
cardiovascular disease in a progeria
10.1161/CIRCULATIONAHA.110.0
mouse
07021
model.
PNAS,
105(41),
15902-15907.
/doi:
10.10.1073/pnas.0807840105
Cellular
Senescence,
doi:
10. Gerhard-Herman, M., Smoot, L. B., Wake, N., Kieran, M. W., Kleinman,
5. Davies, B. S., Barnes, R. H., Tu, Y.,
M. E., Miller, D. T.,…….,, Gordon,
Ren, S., Andres, D. A., Spielmann,
L.
H. P.,..........., Fong, L. G, (2010).
Premature
An accumulation of non-farnesylated
Children With Hutchinson- Gilford
prelamin A causes cardiomyopathy
Progeria Syndrome. Hypertension.
but not progeria. Oxford University
59,
Press.
10.1161/HYPERTENSIONAHA.111
19(13),
2682-94./doi:
10.1093/hmg/ddq158 Lamin
a
Hutchinson-Gilford
(2012).
Mechanisms
Vascular
Aging
92-97./
of in
doi:
.180919
6. De Sandre-Giovannoli A, et al. (2003)
B.
truncation
in
progeria.
Science 300:2055. 7. Eriksson M, et al. (2003) Recurrent
11. Gerhard-Herman M, et al.; American Society
of
Echocardiography;
Society of Vascular Medicine and Biology(2006) noninvasive
Guidelines vascular
for
laboratory
de novo point mutations in lamin A
testing: A report from the American
cause Hutchinson-Gilford progeria
Society of Echocardiography and the
syndrome. Nature 423:293–298.
Society of Vascular Medicine and
15. Leopold, J. A. (2013), Vascular
Biology. J Am Soc Echocardiogr
Calcification: An Age-Old Problem
19:955–972
of Old Age. Circulation,127, 2380-
12. Gordon, L.B., Kleinman, M. E., Miller, D.T., Neuberg, D., GiobbieHurder,
A.,
Gerhard-Herman,
M.,….,
Kieran,
2382/
doi:
10.1161/CIRCULATIONAHA.113.0 0334/
(2012).
16. Li, X., Han, J., Li, L.,Wang, K. J.,
Clinical Trial of a Farnesyltransfrase
Hu, S. J. (2013) . Effect of
Inhibitor
farnesyltransferase
in
M.W. Children
with
inhibition
on
Hutchinson-Gilford
Progeria
cardiac remodeling in spontaneously
Syndrome.
of
hypertensive
National
Proceedings Academy
of
the
Sciences,
109(41), 16666-16671. 13. Gordon,
L.
B.,
rats.
International
Journal Cardiology. 168(4), 33403347./
Massaro,
J.,
doi:
10.1016/j.ijcard.2013.04.038
D’Agostino, R. B., Campbell, S. E.,
17. Masood A. Shammas. Telomeres,
Brazier, J., Brown, W. T.,........ ,
lifestyle, cancer, and aging. Curr
Kieran, M. W. (2014). Impact of
Opin Clin Nutr Metab Care. Jan
Farnesylation Inhibitors on Survival
2011;
in Hutchinson-Gilford
10.1097/MCO.0b013e32834121b1
Progeria
Syndrome. Circulation. 130, 27-34. /doi: 10.1161/CIRCULATIONAHA.113.0 08285 14. Indriana Y. (2006), Progeria: Suatu gangguan
perkembangan
anak.
(Studi longitudinal Tahun II). Temu Ilmiah Nasional IPPI V
14(1):
18. McClintock,
28–34.
D.,
Gordon,
doi:
L.B.,
Djabali, K. (2006). HutchinsonGilford progeria mutant lamin A primarily targets human vascular cells as detected by an anti-Lamin A G608G antibody. PNAS, 103(7), 2154-2159.
/doi:
10.1073/pnas.0511133103 19. NIH researchers find new clues about
aging
,(
2011)(http://progeriaresearch.org/ass
ets/files/pdf/psa_ads/NIH%20Press% 20Release.pdf)
Y., McNair, R., Tajsic, T., Figg,
20. Olive, M., Harten, I., Mitchell., Beers, J., Djabali, K., Cao, K.,….., Gordon,
L.
Cardiovascular
B.
with
(2010).
Pathology
Hutchinson-Gilford Correlation
in
Progeria: the
Vascular
Pathology of Aging. NIH-Public Access Author Manuscript, 30(11), 2301-2309/
doi:
10.1161/ATVBAHA.110.209460. 21. O’Rourke
MF,
22. Ragnauth, C. D., Warren, D. T., Liu,
Staessen
JA,
N.,…….., Shanahan, C. M. (2010). Prelamin A Acts to Accelerate Smooth Muscle Cell Secescence and Is a Novel Biomarker of Human Vascular Aging. Circulation, 121, 2200-2210.
/doi:
10.1161/CIRCULATIONAHA.109.9 02056 23. Scaffidi, P., Misteli, T. (2005). Reversal of the cellular phenotype in the
premature
aging
disease
Vlachopoulos C, Duprez D, Plante
Hutchinson-Gilford
GE (2002) Clinical applications of
syndrome. Nature Medicine, 11 (4),
arterial stiffness; definitions and
440-445.
reference values. Am J Hypertens 15: 426–444.
progeria
24. Sugita, M., Sugita, H. Kaneki, M. (2007). Farnesyltransferase Inhibitor, Manumycin
A,
Prevents
Atherosclerosis Development and Reduces
Oxidative
Stress
in
Apolipoprotein E-Deficient Mice. 27.
1390-1395.
10.1161/ATVBAHA.107.140673
doi:
25. Trigueros-Motos,
M.
27. Verstraeten, V. L. R. M., Ji, J. Y.,
Gonzalez, J. M., Rivera, J., Andres,
Cummings, K. S., Lee, R. T., &
V.
Lammerding, J. (2008). Increased
(2011).
L.,
Jose
Hutchinson-Gilford
progeria syndrome, cardiovascular
mechanosensitivity
disease and oxidative stress. 1(3).
stiffness
1285-1297.
progeria
http://dx.doi.org/10.2741/226
farnesyltransferase inhibitors.Aging
26. Varga R, et al. (2006) Progressive
in
cells:
Cell, 7(3),
in amouse model
9726.2008.00382.x
syndrome.
Proc
103:3250â&#x20AC;&#x201C;3255.
Natl
Acad
progeria Sci
USA
Effects
of
383â&#x20AC;&#x201C;393.
doi:10.1111/j.1474-
Hutchinson-Gilford
nuclear
Hutchinson-Gilford
vascular smooth muscle cell defects of
and
28. What do we know about heredity and progeria? (http://www.genome.gov/11007255) 29. Yang, S.H., Chang S.Y., Andres, D. A., Spielmann, H. P., Young, S. G., Fong, L.G. (2010). Assesing the efficacy
of
farnesyltransferase
protein inhibitors
in
mouse models of progeria. J Lipid Res, 51(2), 400-5.
Tables and figures
Figure 1. Normal Prelamin A Processing and alteration in Hutchinson-Gilford Progeria Syndrome
Figure 2. 93 year-old personâ&#x20AC;&#x2122;s skin without progeria showing massive amount of cells containing progerin.
Table 1. HG(E), HGPS end of therapy; HG(P), HGPS pretherapy. #*Based on Wilcoxon rank-sum test. #†Wilcoxon signed-rank test based on distributions of fold-change (post-/pre-treatment) calculated for each patient
Median density in pixels (range) P value
Site
Percentile Control (n = 55)
HG(P)
HG(E)
Control
HG(P) vs. Control
(n= 22)
(n= 22)
vs.
HG(E)†
HG(P)* Intima media
50
Adventitia luminal
50
near
wall Adventitia deep near wall
!
50
73.0
87.0
72.0
(28.0–
(15.0–
(2.0–
156.0)
242.0)
140.0)
169.0
228.0
170.0
(95.0–
(61.0–
(70.0–
237.0)
254.0)
252.0)
166.0
167.0
121.0
(34–
(30.0–
(12.0–
254.0)
254.0)
215.0)
vs. HG(E)*
0.002
0.002
0.75
0.0004
0.003
0.46
0.32
0.05
0.002
LITERATURE REVIEW Amyloid-Beta (A") antibody Inductor Using Herpes Simplex Virus Type 1 (HSV1) VirusLike Particles as Revolutionary Vaccine for Alzheimerâ&#x20AC;&#x2122;s Disease Athaya Febriantyo P 1
1
,Afriska Chandra P.Y 1, Miranda Puspita Sari 1
Facultry of Medicine, Brawijaya University (AMSA-UB) Abstract
Alzheimer's disease (AD) is a neurodegenerative disorder that occurs in the elderly and it is the most common cause of dementia. These diseases have neurological symptoms such as impaired memory, language, cognitive deficits, emotional and behavioral disorders, such as depression, agitation, and progressive psychosis. Alzheimer prevalence increased from year to year and it will be expected to reach 100 millions by 2050 in the world. So that, this disease is one of the major problems that occur at this time. Accumulation of amyloid-beta (A+) in the brain plays critical role as a risk factor in AD. But there is no potent protection for AD currently in community. One prevention which currently developed is AD vaccine. Vaccine that works on A+ peptide may be an alternative protection. The first developed vaccine shows decrease in A+ plaques and reduction in neuronal pathology but unfortunately discontinued the study due to meningoencephalitis caused by the response of T-cells. Therefore it is necessary to develope vaccine which induces high antibody titer response mechanism to avoid self-tolerance and induction of T-cell responses that can cause inflammation. So one of the solutions is Virus-like Particles (VLPs) as the carrier to avoid those.VLP is a structural proteins of the virus which is non-infectious and it can be used as vaccine against virus of the same derivatives. Recent research indicates that the VLPs can induce high titers of antibodies in humans. So, VLPs can be used as an effective vaccine to form strong antibody response.Herpes Simplex Virus type-1 (HSV1) is an alpha herpes virus. HSV1 VLP can trigger the formation of antibodies against A+ because it has the ability to directly bind to A+. So that, we induce HSV1 VLPs with A+ peptides to make B-cells creating IgG against A+ accumulation in human body and it can be used as a vaccine as a new protection for AD.
Keywords: Invention, Alzheimer's Disease, Amyloid-beta Accumulation, Vaccine, Herpes Simplex Virus type-1, Virus-like Particles
Introduction
greatly to the degeneration of neurons in AD. 2
Dementia is a neurocognitive disease that many occurs in the elderly. Some risk
There are several treatments developed
factors for dementia that causes Alzheimer's
currently for AD. One of them is a vaccine
disease
disease,
that works on amyloid-+ peptide and it can
Meanwhile,
be an alternative immunotherapy in the
Alzheimer's disease is the most common
treatment of AD. Originally found that first-
cause of dementia. Alzheimer's disease
generation vaccine, AN AD-1972, has been
alone is a neurodegenerative disorder that
shown to reduce plaque and to reduce nerve
causes memory loss, language, behavioral
pathology. 3 But the adjuvant in the vaccine
and emotional changes such as depression,
induces T-cells resulting in inflammation
agitation,
AD
that causes meningoencephalitis. Therefore,
increased
it now takes a new revolutionary alternative
simultanously with its risk factors, age.
vaccines that do not induce T-cell responses
Predicted demographic is increased in the
but can induce high antibody titers.
(AD)
Huntington's
prevalence
are
Parkinson's
disease,
progessive is
etc..
psychosis.
progressively
elderly population and it is expected to reach 100 millions by 2050 in the world and it was
VLP or Virus-like Particle is an arrangement
already 616.100 in Indonesia in 2005.
of structural proteins of the virus-like
Therefore, this disease is one of major
viruses where they came from but because it
diseases at this time. 1
has a bit of the viral genome, VLP is noninfectious. Because it has similarities with
Besides age, there are several other risk
the antigen and authentic virions, VLP can
factors such as the accumulation of amyloid
be used as a vaccine against the virus of the
(A+), tau protein hyperphosphorylation,
same derivatives. So that VLPs can be used
cholinergic dysfunction, oxidative stress.
as an effective vaccine because they have
Most cases occur due to accumulation of
particular natural and multivalent structures
A+. A+ itself has fibrilar form which is
that can provoke strong immune response.
neurotoxic to be bonded with one of the
So it can form a strong antibody responses.
neuronal protein Amyloid Precursor Protein
Recent research carried out at the herpes
(APP). This bond later that will contribute
simplex virus and it has been proven in
human. The effect of virus vaccine is safe
formalin and samples for histology were
and it can induce high antibody titers in
processed to paraffin wax by standard
human. 2
methods after macroscopic examination. Tissue
from
unimmunized
AD
cases
HSV1 is the latent virus that has the ability
satisfying CERAD criteria, 10 were drawn
to bind to A+ directly. The interaction
from the archives of the neuropathology
between APP and HSV1 is very significant
laboratory.
because HSV1 directly binds to cellular APP and capable of responding B-cells to create
Data collection methods in this study
IgG against A+ accumulation. Therefore we
conducted by the method of literature
have
vaccine
(literature review) based on issues, both
Alzheivacc as one alternative protection
through digital and non-digital information
against Alzheimer's disease.
from literature such as journals and medical
an
idea
of
making
a
books. Method
literature
The
method
of
conducted
data through
analysis two
approaches, namely: This scientific paper is based on literature review through biomolecular medicine that describes how the Alzheimer's vaccine that is represented by Herpes Simplex Virus type-1 (HSV1) Virus-like Particles (VLPs), which are supposed to act as the inductor-+ antibody amyloid as a mean of protection by inhibiting
+-amyloid
accumulation.
Methods of A" antibody titers. Antibody titers were measured by conducting ELISA. The amount of A+-specific antibody was ultimately detected with a horseradish peroxidase-linked second antibody against human IgG. Methods of neuropathology. All brains in this study were fixed in
1. Method of exposition, that the presented data and facts that may ultimately sought correlations between these data. 2. Analytic methods, namely through the analysis of data or information by giving the argument through logical thinking and were then taken to a conclusion.
Results
passive
vaccinated
APP
mice
using
monoclonal antibodies against A+. From the One potential vaccine which currently
study found a reduction in A+ deposition in
developed is AN-1792. One of the working
the brain.
mechanism of a vaccine that uses a
been vaccinated AN-1792 showed high
combination of aggregation peptide antibody
antibody titer to reduce plaque. 7 And it also
with potential adjuvant showed a reduction
can turn into profitable pathological process.
in
and
(Table 1) Because A+ is a self antigen in
improvement of behavioral deficits in
AD, induction of antibody response to A+
experimental animals such as rats APP12. In
only enables the avoidance response of B-
a phase II clinical trial of human (AN-1792),
cells to suppress the formation of auto-
AD patients immunized with full-length Ab
antibodies. Some groups were observed in
(Ab 1-42) formulated with Th1 adjuvant
vaccinated APP mice showed reduced A+
QS-21. And of vaccination showed a
antibody
decrease in Ab plaque pathology and
nontransgenik. From research AN-1792,
cerebral
amyloid
plaques
3
6
In addition, patients who had
titer
compared
to
mice
reduction in nerve. In addition, vaccination
self-tolerance occurs in A+ vaccination of
may slow down cognitive decline, but this
high-dose
effect is still lacking in success of clinical
adjuvant is strong. However, only about
trial. 4 Unfortunately, research on AN -1972
20% of the subjects in the AN-1792 is
was terminated due to meningoencephalitis
regarded as antibody responders. Thus, self-
in 6% of patients were vaccinated by the
tolerance may be a risk factor in the AN-
AN-1792.
5
(Figure 1. Meningoencephalitis)
(225
microg)
with
QS-21
1792 vaccine. In certain circumstances the B-cells to respond
and
proliferate
through
a
Meningoencephalitis occurs because of the
mechanism that does not require T-cells (T-
response of T-cells to the AN-1792 and
independent). VLP antigen comprising an
other previous developed vaccines, while the
epitope on the surface again. Usually the
benefits of the vaccine produced antibodies
antigen with a long and repetitive epitopes
against the resistance caused by the antigen.
allow crosslinking with immunoglobulin
The role of antibodies supported research on
receptors on the cell surface of B-cell. Early
cellular
events
complex
induced
between
crosslinking
antigen-B
cell
sporadic, but about 10% of patients, there is a history of dementia in family.
10
These
proliferation and differentiation initiated B-
diseases have neurological symptoms such
cells without activating the mechanism of T-
as impaired memory, language, cognitive
cells (T-independent). Previous research has
deficits, and behaviour such as emotional
shown the use of bacteriophage Q+ VLPs
disturbances,
conjugated with A+ 1-6 peptide representing
psychosis and these become increasingly
a success rate of 50% in patients with AD.
severe.
Things precedence in the selection of virus
known, but there are several risk factors for
to be used as VLPs is due to the ability of
AD such as genetic factors, accumulation of
A+ association with VLPs alone carrier is
amyloid, tau protein hyperphosphorylation,
unable to create a bond with A+. The
cholinergic dysfunction, oxidative stress,
interaction between APP and HSV-1 is very
inflammation and dysfunction of synapses.
significant where HSV1 directly binds to the cellular AP where A+ is a product of the metabolism of amyloid precursor protein, type-1 transmembrane protein.
8
So the
making of HSV1 VLPs were conjugated with A+ peptides capable of responding B cells to create IgG against A+ accumulation. 9
11
depression,
agitation,
The cause of AD is not fully
Increased oxidative stress seen in AD patients.
Exposure
to
oxidative
stress
induced accumulation of reactive oxygen species (ROS) that cause damage to proteins, lipids and DNA oxidation in cells. Increased ROS also led to increased accumulation
of
+-amyloid
and
the
formation of senile plaques in AD. ROS will also lead to oxidative stress and is
Discussion
responsible for neuronal cell death. 12
Alzheimer's Disease Alzheimer's
disease
In AD autosomal mutation a protein known (AD)
is
a
neurodegenerative disorder that occurs in the elderly and is the most common cause of dementia. Most cases of AD occur after the age of 50 years with a progressive increase in incidence with age. Most cases are
as the amyloid precursor protein (APP), presenilin 1 and presenilin 2, which causes the
early
onset
abnormalities
and
of
AD.
Intracellular
autonomic
dominant
mutation that causes the death of neurons in AD and the buildup of amyloid. 13
In addition, one sign of lesions in AD is tau
that occur earliest and most common is the
protein hyperphosphorylated. Tau protein
depletion
has been largely studied as a barrier to
colinacetyltransferase). 10
forming a bonded structural and stabilizing microtubules
and
it
is
an
important
of
cholinergic
markers
(eg,
Amyloid-beta (A")
component of the neuronal cytoskeleton. In
Amyloid-beta buildup in the brain is a
the neurons, microtubules form a structure
hallmark of AD. Notching fibrilar on A+ is
that carries nutrients and other molecules
neurotoxic although the mechanism is not
from the cell body toward the end of the
yet fully known. Conversion of fibrilar leads
axon, forming bridges with other neurons. In
to increased bond formation with specific
AD neurons, there was an abnormal
proteins on neuronal membranes, including
phosphorylation of tau protein, a chemical
the amyloid precursor protein (APP). A+-
that causes a change in tau bound to
APP
microtubules can not be together. Spiral
degeneration of neurons in AD. 8
abnormal tau filaments into a double helix around each one was injured. With the collapse of the system of internal transport, intracellular relationship is the first time did not work, and finally followed by the death of cell. 10
interactions
contribute
in
the
A+ is a product of the metabolism of amyloid precursor. Autosomal dominant AD caused by genetic mutations of APP or presenilin. Such mutations lead to changes in the process of making the production of A+ APP or a 42-amino acid to form A+
Chemical changes in the central nervous
increases. While A+ itself has properties
system (cholinergic dysfunction) are also
require aggregation of A+ neurotoxicity
found in AD. The cortex of the human brain
neurotoxic
consists of a large number of cholinergic
characterized by increased amyloid fibrils
axons that release acetylcholine, a key
similar to mature amyloid plaques. 8
neurotransmitter in cognitive function. Most cholinergic axons inhabit so much cortex and hippocampal cholinergic neurons which are damaged in degenerative changes that occur
in
AD.
In
neurochemistry,
abnormalities in the brains of AD patients
and
peptide
which
is
In vivo, it is also mediated by neurotoxic A+ peptide
formation
pathological
fibrilar
characteristics
with
some
of
AD.
Neurotoxic mechanisms of A+ is not known, but some say the alleged influence of the
increase of free radicals. As for other
cortical culture in APP mice. In addition, the
potential mechanisms of the interaction that
cortical culture was also found that the APP
A+ activates receptors on the surface of the
can
groove. This mechanism is also associated
interaction of A+ with the normal cellular
with the induction of phosphorylation of A+
precursors
and tau protein phosphorylation of adhesion
degeneration through a mechanism of
kinase. 8
pathogenic prion. 8
The relationship between neurotoxic A+ and
Virus Like Particle (VLP)
normal biological function is not known. However, the structure of APP (Amyloid precursor protein) may has function as receptors on the cell surface. APP can mediate cell adhesion and stimulates the development of neurit through interactions with extracellular proteins. Additionally secretions released by the APP itself can stimulate cell proliferation and function as neuroprotective against various toxic as oxidative stress, glucose deficiency and eksotositosis. But so far, it is not known for certain whether APP is involved in the mechanism of neuronal degeneration in ADterlepas from its role as a precursor of A+. 8
modulate
A+
that
toxicity.
can
Thus
lead
to
the nerve
Several protein structures have an intrinsic ability
to
become
virus-like
particles
(VLPs). The structure of the VLP resemble the virus from which they were derived but because it has a bit of the viral genome, VLP is non-infectious. Because it has similarities with the antigen and authentic virions, VLPs can be used as a vaccine against the virus of the same derivatives. VLP-based vaccines are used to prevent infection.
11
Hepatitis B
virus and human papilloma virus that has been proven in humans. The effect on both virus vaccine is safe and these can induce high antibody titers in human.
14
VLP-based
vaccine developed clinical and preclinical as imunoprophylactic against the infectious 15
Formation of toxic A+ fibrilar binding to
virus to human.
membrane proteins including APP neurons
effective
with high affinity. A+ interacts with holo-
particular natural and multivalent structures
APP to a lesser extent with the secretions
that
that are part of the soluble A+ APP.
response. Particular structure is crucial to
Neurotoxicity
significantly
reduced
in
can
vaccine provoke
VLPs can create an because an
they
strong
have
immune
improve the interaction with B-cells that can
proliferation and differentiation of cells
form a strong antibody response.
initiate B to further interact with Th cells. 7
Virus Like Particles (VLPs) Induce
Herpes Simplex Virus associated with
Antibody Formation
APP
Antibody production is initiated by the
Herpes Simplex Virus type-1 (HSV1) is an
interaction between antigen and B-cell
alpha herpes virus is endemic in a
receptor (BCR) on the surface of a naive B-
population. The virus causes latent infection
cells. Response speed of B-cells to antigen
in neurons lifetime.
stimulation is determined by the density of
that,
the antigen, thus also affecting the speed of
nucleocapsid core transported out through
antibody
the cytoplasm to the surface of epithelial
response.
Antigen
having
through
assembly
HSV
Meanwhile, anterograde transport synthesis
responses at lower concentrations than the
of the new virus on the cell surface of
monomeric antigen and without the need for
epithelial and neuronal cell bodies to the
exogenous adjuvant.
mucous membrane of the virus is essential
Antigen consisting of repeated epitopes on the surface at a distance 5-10 nm in most viruses
can
induce
neuron.
17
antibody
7
and
the
activate
induce
sexual
of
cells
and
both
As with other viruses
multivalent structures such as VLPs can B-cells
in
16
B-cell
responses
for propagated virus to a new host in both the cellular and molecular mediators of virus.
optimally. 7 Multivalent antigen can provoke
Coordinating assembly in epithelial cells
high BCR for the formation of stable lipid
and neurons as well as various types of
mikrodomain that can affect an increase in
alpha herpes virus may be different and still
the signal to B-cell. These signals stimulate
be a controversy. Recent evidence suggests
the proliferation and differentiation of B-
that swine alpha herpes virus, pseudorabies
cells. This is because the antigens with
virus (PRV) in the vesicle membrane
repetitive epitopes allow crosslinking with
transport on neuron. 18 It is a mechanism that
immunoglobulin
will induce anterograde transport epithelial
receptors
on
the
cell
19
surface induced premature B-cellular. This
cells HSV1.
HSV1 capsid new synthesis
complex crosslinks between antigen-B cell
walks alone out of the nucleus to be assembled with other components in the
cell.
20
Electronmicroscopy from infected
in explaining the mechanism of toxicity in
cells showed that the capsid-free in the
vitro. In APP molecule, residues 1-28 of A+
cytoplasm as well as membrane systems that
region is often referred to as the N-terminus
are at intracellular. To
coordinate
19
and the 36-42 hydrophobic residues are
wrapping
mechanism
(envelopment) with transport, the virus must take advantage of the cellular synthesis and transport
machinery.
Backup
transport
machinery may underlie the pathology of HSV-1 provider, injure cells by interfering with normal cellular processes. Use of Green Fluorescent Protein (GFP) in HSV1 as a tool to reveal the cargo receptor motors are used to find the provider and the APP transmembrane
glycoprotein
that
is
a
component of intracellular HSV1 virus particles. Changes in APP is a risk factor for the disease Alzheime. But APP interaction HSV1 has significant potential in the prevention of Alzheimer's disease. 20
often referred to as A+ C-terminus. Residues 1-28 are in the extracellular domain, outside the cell membrane, whereas residues 29-43 are anchored in the lipid membrane. Hydrophobic region of A+ peptide folding directs a beta-sheet forming lipids, thereby inducing fibrillation and aggregation of the peptide. Research shows that the more toxic A+ fibriler of the monomer, and together with the fact that Ab longer before the onset of AD in patients carrying APP have been found to support the production of A+ peptides again. Hydrophobic regions of the peptide has also been shown to have properties
that
can
do
fusogenic
destabilizing cellular membranes. Various studies have provided strong evidence that
The role of A" in the cell due to
A+
degenerative oxidative stress
development and progression of AD. Study
plays
an
important
role
in
the
of embryonic neurons were incubated with A+ 1-40 is the major A+ species and quite
primary Ab has shown that peptides can
late, while Ab 1-42 (and 1-43 Ab) is a small
produce neurotoxic. Several studies have
species, less soluble and easily aggregate
shown that A+ causes neurotoxicity by
into fibrils, as exhibited in amyloid plaques.
inducing the production of free radicals.
As it has been shown by several groups that
Further studies then showed that A+ caused
the various regions of A+ peptides have
H2O2 accumulation in hippocampal neurons.
certain characteristics that may be important
It has also been shown that A+ induces lipid
16
peroxidation and that A+ may lead to excess
optimal.
production
by
high BCR for the formation of stable lipid
interaction with vascular endothelial cells.
mikrodomain that can affect an increase in
This process can lead to the production of
the signal to B-cell. These signals stimulate
harmful hydroxyl radicals through Fenton
the proliferation and differentiation of B-
reaction. Hydroxyl radicals are highly
cells. This is because the antigen with a
reactive molecules that can damage any
lengthy
nearby.
crosslinking with immunoglobulin receptors
of
superoxide
radicals
Multivalent antigen can provoke
and
repetitive
epitopes
allow
on the cell surface induced premature B-cell. (Figure 2. The mechanism of free radical
This complex crosslinks between antigen-
formation by A")
initiated cell proliferation and differentiation of B cells without activating the mechanism
VLPs as antibody inductor
of T-cell (T independent ). 16
Antibody production is initiated by the
The
interaction between antigen and B-cell
through the activation of T-cells (T-
receptor (BCR) on the surface of a naive B-
dependent) that can cause inflammation and
cells. Response speed of B-cells to antigen
mechanisms of VLP as an inductor antibody
stimulation is determined by the density of
that is not through the mechanism of T-cell
the antigen, thus also affecting the speed of
activation can be explained in figure 3 and
antibody response. Multivalent antigen that
figure 4 below.
difference
in
antibody
formation
has a structure composed of repetitive epitopes such as VLPs can activate B cells
(Figure 3. Formation of Antibody via T-
and induce antibody responses at lower
dependent mechanism)
concentrations than the monomeric antigen and without the need for exogenous
B-cells can be activated in 2 ways namely
adjuvant. 16
the T-dependent and T-independent. On Tdependent antigen after bound with mIg, B-
Antigen consisting of repeated epitopes on
cells eat antigen, process and express MHC
the surface at a distance 5-10 nm in most
epitopes in the gap and presented to T-cells.
viruses can induce B cell responses in
T-cells modulate B-cell function through
cytokines that will promote the proliferation
Previous research has shown the use of
of B-cells and differentiate into plasma cells,
bacteriophage Q+ VLPs conjugated with A+
which then become antibody. But instead of
1-6 peptide representing a success rate of
stimulating the proliferation of B-cells, T-
50% in patients with AD. Things precedence
cells can also activate macrophages and
in the selection of virus to be used as VLPs
inflammatory mediators. Inflammation in
is due to the ability of A+ association with
the brain is very dangerous and lead to
VLPs alone carrier is unable to create a bond
meningoencephalitis.
with A+. The interaction between APP and HSV1 is very significant where HSV1
(Figure 4. Antibody Formation Through T-
directly binds to the cellular AP where A+ is
independent mechanisms such as VLPs)
a product of the metabolism of amyloid precursor protein, type-1 transmembrane 8
In certain circumstances the B cells to
protein.
respond
a
were conjugated with A+ peptides capable
mechanism that does not require T-cells
of responding B cells to create IgG against
(T-independent). VLP antigen comprising
A+ accumulation. 5
and
proliferate
through
So the making of HSV1 VLPs
an epitope on the surface again. Usually the antigen with a long and repetitive epitopes
Conclusion
allow crosslinking with immunoglobulin receptors on the cell surface of B. Early cellular
events
complex
induced
between
crosslinking
antigen-B
cell
1. Formation of amyloid-beta (A+) is the cause of most of the risk factors for AD. The mechanism of accumulation of A+
proliferation and differentiation initiated B-
due
cells without activating the mechanism of T-
establishment which is neurotoxic A+
cells
fibrilar causing neurotoxicity by inducing
(T-independent).
inflammation
It
can
which
prevents
lead
to
meningoencephalitis.
to
the
conversion
of
the
the production of free radicals in hippocampal neurons. Conversion bind to specific
proteins
on
the
neuronal
HSV1 VLPs triggers the formation of
membrane, the amyloid precursor protein
antibodies against amyloid-"
(APP). A+-APP interactions contribute in neuronal cell degeneration in AD.
2. Several protein structures have an
2.
Poovorawan
Y,
Chongsrisawat
V,
intrinsic ability to become Viral-like
Theamboonlers A, Bock H, Leyssen M,
Particles (VLPs). VLPs resemble the
Jacquet JM.(et al.). Persistence of antibodies
virus from which they originate but have
and immune memory to hepatitis B vaccine
little viral genome, so VLP is non-
20
infectious. Because it has similarities
Thailand. 2010. p730-736.
with the antigen and authentic virions, VLPs can be used as a vaccine against the virus of the same derivatives. The working mechanism of the VLP is to activate B-cells and to induce antibody responses at lower concentrations than
3.
years
after
infant
Satpute-Krishnan
Fastanterograde simplex
virus:
vaccination
P,
De
transport role
Giorgis.
tof
for
in
the
herpes amyloid
precursor protein of alzheimer’s disease. 2003. V2 : p305–318.
the monomeric antigen and without the
4.
need for exogenous adjuvant.
translocations in virus replication. 2002.
3. HSV1 VLPs can trigger the formation of
Willard
M.
Rapid
directional
p5220–5232.
antibodies against A+ because it has the
5. Snyder A, Polcicova K. Herpes simplex
ability to bind to A+ directly. The
virus IgE/IgI and US 9 proteins promote
interaction between APP and HSV1 is
transport of both capsids and virionglyco
very significant because HSV1 directly
proteins
binds to cellular APP. HSV1 VLPs
(l82):10613–10624.
conjugated with A+ peptides are capable of responding B-cells to create IgG against A+ accumulation.
in
neuronal
axons.
2008.
6. Dodart J, Bales K, Gannon K, Greene S, DeMattos
R,
Immunization
Mathis reverses
C.
(et
memory
al.). deficits
without reducing brain Abeta burden in
References 1. Alzheimer Association. Prevalence of
Alzheimer’s disease model. 2002. p452-427.
Alzheimer Diseases and other Dementias.
7. Geldmacher D. Differential diagnosis of
In:
Alzheimer’s disease. Neurology.
Alzheimer
Association
(eds.)
Alzheimer's Facts and Figures. 8th ed. United
States
of
America:
Association. 2012. p14-16.
Alzheimer
(48):31-35.
1997
8. Alfredo. Amyloid " interacts with the
15. Poovorawan Y, Chongsrisawat V,
amyloidprecursor protein: a potential toxic
Theamboonlers A, Bock H, Leyssen M,
mechanism in Alzheimer’s disease .2000 Vol
Jacquet JM.(et al.). Persistence of antibodies
3 no V: 460.
and immune memory to hepatitis B vaccine
9. Smith M, Casadesus,G, Joseph. Amyloidbeta and tau serve antioxidant functions in
20
years
after
infant
vaccination
in
Thailand. 2010; (28):730-736.
the aging and Alzheimer brain. 2002;
16. Janus C, Pearson J, McLaurin J,
(33):1194–1199.
Mathews P, Jiang Y, Schmidt SD. (et al.). A
10. Karran E, Mercken M.. The amyloid cascade hypothesis for Alzheimer’s disease: an appraisal for the development of therapeutics. 2011; (10):698–712. 11. Brookmeyer R, Forecasting
the
Johnson E, global
Zigler.
burden
of
Alzheimer’s disease. 2007; (3):186-191. 12. Mettenleiter T . Herpes virus assembly an degress. 2007; (76): 1537–1547.
Schmid M, Pumpens P, Bachmann M (et al.). Regulation of IgG anti-body responses by epitope density and CD21-mediated costimulation. 2002; (32):3305-3314.
oxidativestress-induced cell death of human age-
matched olfactory neuroepithelial cells via suppression of intracellularreactive oxygen species. 2009; (17): 611-619.
immunization
reduces
behavioural impairment and plaques in a model of Alzheimer’s disease. 2000; (408):16. 17. Von B. R. Glial cell dysregulation: a new perspective on Alzhemier disease. 2007; (12): 215-232. 18. Loret S, Guay G. Comprehensive characterization of extracellular herpes virus
type
1
virions.
2008;
(82):8605–8618. 19. Masliah E, Hansen L, Adame A, Crews L, Bard F, Lee C.( et al.). Abeta vaccination effects on plaque pathology in the absence of encephalitis in Alzheimer disease. 2009;
14. Nelson V, Dancik C. PAN-811 inhibits and
peptide
simplex
13. Jegerlehner A, Storni T, Lipowsky G,
Alzheimer’sdisease-derived
beta
(64):129-131. 20. Kumar V. (et al). Buku Ajar Patologi. 7th ed,
Vol.
1.
Jakarta:
Penerbit
Kedokteran EGC, 2007: 189-1.
Buku
Tables and figures
Figure 1
Figure 2
Figure 3
Figure 4
Table 1
LITERATURE REVIEW Innovetion for Osteoporosis Vaccination: The Role of Anti-Sclerostin Antibody as Sclerostion Inhibitor in Osteoporosis Prevention on High Risk Geriatric People Kharisma Ridho Husodo 1, Thoha Muhajir Albaar 1, Rahadi Akbar 1 1
Faculty of Medicine, Brawijaya University(AMSA-UB) Abstract
Osteoporosis is a silent disease characterized by low bone mass which are associated with reduced bone strength and increase of fracture risk. Osteoporosis is the second worldwide disease problem after heart disease. Osteoporosis occurs because the unbalanced activity of osteoclast as a bone resorption cells and osteoblast as a bone formation cells tha. Osteoporosis occurs both men and women, but mostly on postmenopausal women older than 50 years old. Initial therapy for osteoporosis treatment due to menopause is anti-resorptive agent that can not stimulate bone formation, also paratyroid hormone (PTH) that can stimulate bone formation, but also has ability to stimulate bone resorption so become less effective. Recent study show that antibody anti-sclerostin can stimulate bone formation without stimulating bone resorption. So one of the solution is to induce antibody anti-sclerostin as the prevention of osteoporosis in high risk geriatric people.Sclerostin is a protein produced by SOST gene expressed by osteocytes in the human bone. Sclerostin act as a negative regulator in the bone formation. Individu with sclerostin deficiency has high bone mass, increased bone strength, and resistance to fracture. Sclerostin works by inhibiting the Wnt and bone morpho-genetic protein signaling pathways that are critical for osteoblast proliferation and activity. Monoclonal antibodies were obtained and characterized using bacterially expressed and insect cellâ&#x20AC;&#x201C;expressed recombinant scl. Inhibition of sclerostin by systemic adminitration of Anti-sclerostin monoclonal antibody increased bone formation, bone mass, and bone strength in non-fractured bones in non human primate models.! So this antibody-mediated blockade of sclerostin represents a promising new preventional approach for the anabolic prevention of people with high risk bone-related disorders,such as postmenopausal osteoporosis. Keywords: Osteoporosis, Sclerostin, Wnt Signalling, Monoclonal Antibody
Introduction
paratyroid hormone (PTH) peptide has
Osteoporosis is silent disease which can weaken the bone and refered to cause fracture. WHO state that osteoporosis is disease as world health problem after cardiovascular disease. A study showed that women with 50 years old have a risk to die due to hip fracture which have same risk with breast cancer after got menopause which causes estrogen level decreased
ability to stimulate bone formation. But, PTH also has ability to stimulate bone resorption so stimulation which is given before become less in effectivity. In some cases, we can conclude that new innovation is needed in osteoporosis treatment which can stimulate bone formation
without
stimulating bone resorption. (Papapoulos, 2011).
which has a important role in keeping bone from fragility. In Indonesia at 2005, osteoporosis affected 29,4% at 60-64 years old people; 36,4% at 65-69 years old people and 53,1% at 70 years old people or higher. (Fatmah, 2008).
osteoclast (bone resorber) and shorten lifespan of osteoblast (bone formation) due decreased
estrogen
level
causes
imbalance of bone formation and bone resorption). This imbalane cause bone strenght
worse
and
bone
fragilty
increased.(Papapoulos, 2011).
due
formation by osteoblast. Sclerostin has an important role in bone remodelling process
to
menopause
inhibit osteoblast activityl. In present, some researchers
have
monoclonal
antibody
been
developing
(mAb)
for
anti-
sclerostin. Pre-clinical and clinical studies showed that sclerostin inhibition has strong effect in stimulating of osteoblastic bone formation.
(Papapoulos,
2011).
This
monoclonal antibody anti-sclerostin has a potency not only for ostephoroisis treatment
Nowadays, initial therapy for osteoporosis treatment
which has a role as down-regulator in bone
because it is a protein which has ability to
In osteoporosis, prolonged lifespan of
to
Sclerostin is protein secreted by osteocyte
is
anti-
resorptive agent which can only prevent bone degradation but it can not stimulate bone formation. A study showed that
but also others bone disorder.(Lewiecki, 2011). Some of researches about sclerostin showed a new novel for osteoporosis prevention based on vaccination principle. Vaccination is still limited to tropical
disease only, but some new studies showed
2. Analytic methods, namely through the
that antibody formation against a specific
analysis of data or information by giving the
target has a big chance as new prevention
argument through logical thinking and were
strategy for degenerative diseases. In this
then taken to a conclusion.
paper, we want to know how monoclonal antibody
anti-sclerostin
has
effect
in
Results and Discussion
decreasing bone resorption and increasing bone formation for osteoporosis prevention.
Osteoporosis is a progressive bone disease
Methods
that is characterized by a decrease in bone
This scientific paper is based on literature review through biomolecular medicine that describes how the Osteoporosis vaccine that is represented by monoclonal antibody antisclerostin, which are supposed to act as the inhibitor of sclerostin which has effect in increasing bone formation and decreasing bone resorption.
conducted by the method of literature (literature review) based on issues, both through digital and non-digital information from literature such as journals and medical literature
The
method conducted
mass and density which can lead to an increased risk of fracture. Osteoporosis is the most common metabolic bone disease in the United States and can result in devastating economic
physical,
psychosocial,
consequences.
It
is
and often
overlooked and undertreated, however, in large part because it is so often clinically silent before manifesting in the form of
Data collection methods in this study
books.
Osteoporosis Disease
of
data through
analysis two
approaches, namely:
fracture.(Kosmin et al, 2014). Osteoporosis is a silent disease. A person might not know got it until broken bone occured. A bone mineral density test is the best way to check bone health. To keep bones strong, eat a diet rich in calcium and vitamin D, exercise and do not smoke. If needed, medicines can also help.(National Institutes of Health, 2014).
1. Method of exposition, that the presented
Bone is continually remodeled throughout
data and facts that may ultimately sought
our lives in response to microtrauma. Bone
correlations between these data.
remodeling occurs at discrete sites within
the skeleton and proceeds in an orderly
various
disease
states
fashion, and bone resorption is always
medications.(Kosmin et al, 2014).
and
followed by bone formation, a phenomenon referred to as coupling.(Mayoclinic, 2014). Osteoclasts, derived from mesenchymal cells, are responsible for bone resorption, whereas osteoblasts, from hematopoietic precursors,
are
responsible
for
bone
formation. The 2 types of cells are dependent on each other for production and linked in the process of bone remodeling. (Kosmin et al, 2014).
Aging and loss of gonadal function are the 2 most important factors contributing to the development of osteoporosis. Studies have shown that bone loss in women accelerates rapidly
in
the
first
years
after
menopause.(Carlyn Becker, 2014). The lack of gonadal hormones is thought to upregulate osteoclast progenitor cells. Estrogen deficiency leads to increased expression of RANKL by osteoblasts and decreased
The hallmark of osteoporosis is a reduction
release of OPG; increased RANKL results in
in skeletal mass caused by an imbalance
recruitment
between
bone
preosteoclasts as well as increased activity,
formation. Under physiologic conditions,
vigor, and lifespan of mature.(Kosmin et al,
bone formation and resorption are in a fair
2014).
bone
resorption
and
of
higher
numbers
of
balance. A change in either (increased bone resorption or decreased bone formation)
Genetic and phenotypic analysis of the
may result in osteoporosis.(Mayoclinic,
extremely rare high bone mass disease,
2014).
sclerosteosis, led to the discovery of the protein sclerostin and de!ned its function as a key negative regulator of bone mass and
Osteoporosis can be caused both by a failure
bone formation. Sclerostin, encoded by the
to build bone and reach peak bone mass as a
SOST gene,is a secreted, cystine-knot
young adult and by bone loss later in life.
glycoprotein expressed primarily in bone,
Accelerated bone loss can be affected by
speci!cally by osteocytes.(Li et al, 2009).
hormonal
in
Sclerostin de!ciency in humans, together
perimenopausal women, can impact elderly
with the data from SOST knockout mice,
men and women and can be secondary to
suggests that sclerostin inhibition might be
status,
as
occurs
aviable approach for the development of novel anabolic agents.(Kosmin et al, 2014). Of note, the marked increase in bone mass found in these genetic cases of life-long sclerostin de!ciency includes the early stage of life that is normally characterized by rapid skeletal growth and bone mass accrual.As such,it is not known what the extent and magnitude of sclerostinâ&#x20AC;&#x2122;s role is in the control of bone formation and bone
Sclerostin Sclerostin is a protein produced exclusively in the skeleton by osteocytes. The role of sclerostin in bone remodelling cycle is the negative
regulator
of
bone
formation.
Sclerostin is encoded by SOST gene which is located on chromosome 17q12-21. SOST gene defects can lead to sclerosteosis and van Buchem disease. (Papapoulos, 2011).
mass during the clinically important later stages of life,when bone mass accrual has ceased and when the incidence of bonerelated disorders, such as post menopausal osteoporosis(PMO), is highest. (Li et al, 2009).
Sclerosteosis and van Buchem disease are two rare sclerosing bone disorders, which were first described in the 1950s as distinct clinical
entities
with
closely
related
phenotypes. The defect of the SOST gene decreased the production of sclerostin by
A study introduces a humanized monoclonal
osteocytes. This leads to an increase in
antibody directed against the osteocyte-
osteoblastic bone formation and the typical
derived glycoprotein known as sclerostin.
bone phenotype. The skeletal manifestations
Humans
of both diseases result from endosteal
with
genetic
deficiencies
of
sclerostin and mice with knockout of the
hyperostosis,
sclerostin gene (SOST) have high bone
progressive generalised bone overgrowth
mass,
and
and thickening and are most pronounced in
resistance to fracture. Sclerostin works by
the mandible and the skull. (Moester et al,
inhibiting the Wnt and bone morpho-genetic
2010)
increased
bone
strength,
are
characterised
by
protein signaling pathways that are critical for osteoblast proliferation and activity. By inhibiting sclerostin, this agent should
Osteocyte-produced
enhance
bone formation by inhibiting the terminal
osteoblastic
Becker, 2014).
function.(Carolyn
sclerostin
decreases
differentiation of osteoblasts and promoting
their apoptosis. Sclerostin was originally
proteins for binding to these co-receptors.
thought to be a BMP (Bone Morphogenetic
Sclerostin may be transported to the bone
Protein) antagonist based on its amino acid
surface via the canaliculi or it may induce
sequence
DAN
another signal in osteocytes, which contain
gene
Wnt signalling, that is transported to
similarity
(differential
with
the
screening-selected
aberrative in neuroblastoma) family of
osteoblasts
secreted glycoproteins that share the ability
(Moester et al, 2010)
to antagonise BMP activity. It was shown, however,
that
sclerostin
could
not
antagonise all BMP responses and had a mechanism of action distinct from that described for classical BMP antagonists, decreasing bone formation by inhibiting the Wnt
signalling
pathway
in
osteoblasts.(Bezooijen et al, 2004) Wnt signaling may play an important role in the anabolic
response
to
deformation
and
loading since increased Wnt signaling has been found after loading of osteoblastic cells in vitro and of tibiae in vivo. Sclerostin antagonizes
Wnt
signalling
and
binds
directly to the first YWTD-EGF repeats of LRP5 (Low Density Lipoprotein (LDL) Receptor-related Protein 5) which is a coreceptor of Wnt and this binding is decreased in the mutated form of LRP5, which is associated with the high bone mass phenotype
(Sawakami
et
al,
2006).
However, although sclerostin binds to LRP5/6 and antagonizes Wnt signalling, it does not appear to compete with Wnt
to
inhibit
bone
formation.
Monoclonal Antibody Monoclonal
antibody
are
monospecific
antibodies that are made by identical immune cells that are all clones of a unique parent cell, in contrast to polyclonal antibodies which are made from several different
immune
cells.
Monoclonal
antibodies have monovalent affinity, in that they bind to the same epitope. Human monoclonal antibodies (mAbs) are the fastest-growing
category
of
mAb
therapeutics entering clinical study.(Nelson et al, 2010). Monoclonal antibodies are used to treat many diseases, including some types of cancer. To make a monoclonal antibody, researchers first have to identify the right antigen to attack.(American Cancer Society, 2014). Producing mAb requires immunizing an animal, usually a mouse, obtaining immune cells from its spleen and fusing the cells with a cancer cell (such as cells from a myeloma) to make them immortal, which
means that they will grow and divide
by the US Food and Drug Administration
indefinitely. A tumor of the fused cells is
(FDA). Since then, an additional six human
called a hybridoma, and these cells secrete
mAbs
mAb.
The development of the immortal
panitumumab, golimumab, canakinumab,
hybridoma requires the use of animals, no
ustekinumab, ofatumumab and denosumab.
commonly accepted nonanimal alternatives
(Nelson et al, 2010).
have
received
FDA
approval:
are available. (National Academy Press, 1999).
Mechanism
of
Monoclonal
Antibody
Anti-Sclerostin formation The mouse method is generally familiar,
Monoclonal antibodies (mAbs) are produced
well understood, and widely available in
by cell lines or clones obtained from animals
many laboratories, but the mice require
that
careful watching to minimize the pain or
substance that is the subject of study. The
distress that some cell lines induce by
cell lines are produced by fusing B cells
excessive accumulation of fluid (ascites) in
from the immunized animal with myeloma
the abdomen or by invasion of the
cells. (Li et al, 2009). To produce the
viscera.(National Academy Press, 1999).
desired mAb, the cells must be grown in
The tissue-culture method would be widely
either of two ways: by injection into the
adopted if it were as familiar and well
peritoneal cavity of a suitably prepared
understood as the mouse method and if it
mouse (the in vivo, or mouse ascites,
produced the required amount of antibody
method)
with every cell line; but culture methods
culture.(National Academy Press, 1999).
have been expensive and time-consuming
In this paper, the procedure to produce anti-
and often failed to produce the required
sclerostin monoclonal antibodies is reffered
amount of antibody without considerable
to Craig et al (2009). Sclerostin peptides
skilled manipulation.
However, culture
with limited homology to sclerostin domain-
methods are now becoming less expensive,
containing protein-1 were synthesized using
more
widely
f-moc chemistry. Sequences were as follows
available.(Mayoclinic, 2014 ; American
: sclerostin mouse peptide 61-78, 61-
Cancer Society, 2014).!In 2002, adalimumab
GRPPHHPYDAKDVSEYSC-78
became the first human mAb to be approved
and mouse sequences are not identical but
familiar,
and
more
have
been
or
by
immunized
in
with
vitro
the
tissue
(human
are similar); and sclerostin human peptide
affinity chromatography (Fig. 1B, right
168-183 plus an extra cysteine for KLH
lane).(Craig et al, 2009). Antibody isotyping
(Keyhole limpet hemocyanin) conjugation,
showed that the antibody directed against
168-KRLTRFHNQSELKDFG-183
C
the COOH-terminal region of the protein
(human and mouse sequences are identical).
had an IgG2bK isotype. Both antibodies
Monoclonal antibodies were generated using
recognized a single band at the same Mr as
standard methods which is reffered to Ezzat
that observed on Coomassie and silver
et al (2008). Hybridoma supernatants were
staining.
initially screened in 96-well plates for
Sensorgram series using HBS-EP exhibited
sclerostin antibodies by ELISA assays using
a KD of "3 , 10*9 M for the amino-
bacterially
terminal antibody and a KD of "8 , 10*9 M
expressed
sclerostin-maltose antigen,
and
phosphatase
human
binding
anti-mouse for
detection.
+
24-213
protein
as
IgG-alkaline Following
cloning, production of antibodies by positive clones
was
verified
by
SDS-PAGE
(Bezooijen
et
al,
2004).
for the carboxyl-terminal antibody for the bound sclerostin. (Craig et al, 2009). (Figure 1 SDS-PAGE and Immunostaining of scl)
multichannel immunoblotting. Isotyping of
Figure 1. show (A) SDS-PAGE of scl. Left
scl MAbs was carried out using the IsoStrip
and middle lanes, scl after nickel-affinity
Mouse Monoclonal Antibody Isotyping Kit.
chromatography. Coomassie (left) or silver
(Craig et al, 2009).
(middle) stain; right lane, scl after final Mono S chromatography (silver stain). (B)
The MAb directed against the NH2-terminal
Immunostaining of scl with anti-scl MAb.
sclerostin sequence detected the protein in
Left lane, scl immunostaining with MAb
the medium and, after purification, by
directed against scl NH2-terminal peptide;
nickel-affinity chromatography (Fig. 1B, left
middle lane, scl immunostaining after
and middle lanes). Antibody isotyping
nickel-affinity chromatography with MAb
showed that the antibody directed against
directed against scl NH2-terminal peptide;
the NH2-terminal region of the protein had
right lane, scl immunostaining after nickel-
an IgG2aK isotype. The MAb directed
affinity chromatography with MAb directed
against the C-terminal sclerostin sequence
against scl COOH-terminal peptide. (Craig
recognized purified protein after nickel-
et al, 2009).
Potency of Monoclonal antibody anti-
reversed completely ovariectomy-induced
sclerostin in increasing bone formation
bone loss, but it further increased bone mass
and decreasing bone resorpion
and bone strength to levels greater than those of sham-operated control animals ( Bone biopsies showed that bone formation
In
patients
with
sclerosteosis,
the
markedly increased in trabecular as well as
combination of high bone mass due to
in periosteal, endocortical and intracortical
increased bone formation with premature
surfaces, leading to increases in trabecular
termination codons in the SOST gene
and cortical thickness and reduction in
suggested an inhibitory effect of the gene
cortical porosity. (Ominsky et al, 2010)
product sclerostin on bone formation. Sclerostin was also shown to stimulate the apoptosis of osteoblasts to decrease their life span.
Furthermore,
analysis
of
SOST
knockout mice showed significant increases in
radiodensity,
(BMD),
cortical
bone and
mineral trabecular
density bone
volume, bone formation rate, and bone strength. Together these data support a negative effect of sclerostin on bone formation. (Li et al, 2008)
Another
studies
about
antibody
anti-
sclerotin also gave similar results. The study compared antibody anti-sclerostin named AMG 785 with teriparatide, the onlu osteoanabolic drug currentlu approved by the US Food and Drug Administration (FDA) for treatment of osteoporosis.The BMD response at the lumbar spine and hip 3 months after a single dose of AMG 785 10/mg/kg SC (Padhi et al., 2011) was similar to or greater than what was seen after
Monoclonal antibody anti-sclerostin work against sclerostin negative effect on bone formation. In a study of ovariectomised rats given antibody anti-sclerostin, the result was a dramatic increase in bone mass and improvement in strength in virtually all skeletal sites. Remarkably, this short-term treatment with sclerostin antibody not only
6 months of daily teriparatide (McClung et al., 2005). The increase in bone formation markers 1 month after receiving AMG 785 in the phase 1 clinical trial (Padhi et al., 2011) was similar to that seen with teriparatide at 6 months (Chen et al., 2005), suggesting osteoanabolic
a
more effect
compared to teriparatide.
rapid with
onset AMG
of 785
(Table 1. Clinical trial development of
which point the study was terminated. Two
AMG 785 for the treatment of osteoporosis)
weeks of Scl-AbII treatment resulted in a
Table 1 show AMG 785, a humanized sclerostin monoclonal antibody, was first studied in humans in a phase 1 randomized, double-blind, placebo-controlled, ascending single-dose study in 72 healthy men and postmenopausal women (Padhi et al., 2011)
rapid increase in BMD at the LV and femurtibia, and by 3weeks, BMD was restored back to sham levels. The !nal 2weeks of Scl-AbII treatment further increased BMD to levels signi!cantly above those of sham control animals at both skeletal sites. At the 5weeks timepoint, BMD in Scl-AbII–treated
Effectivity of Monoclonal antibody anti-
OVX rats was increased by 26% at LV and
sclerostin in Osteoporosis prevention
17% at femur-tibia relative to baseline,
In study which had done by Li et al (2009),
whereas BMD in the sham and OVX
they did a research to analyze sclerostin
controls remained at pretreatment levels.
antibody whether increase bone formation in
Consistent with the rapid increase in BMD,
rat model of postmenopausal osteoporosis.
serum
In this study, to determined whether Scl-
increased after 1week of Scl-AbII treatment
AbII could reverse estrogen de!ciency–
(81.4±8.2ng/ml) compared with levels found
induced
aged
in vehicle-treated OVX control animals
OVX(ovariectomized) rats were treated with
(29.2±2.3ng/ml; p <0.001). There after,
Scl-AbII for 5weeks. Six-month-old female
serum osteocalcin in OVX rats treated with
rats underwent OVX or sham surgery and
Scl-AbII gradually decreased but remained
were aged for 13 month. At the age of 19
signi!cantly elevated throughout the study
month, just before treatment, in vivo DXA
compared with OVX vehicle controls.(Li et
analysis con!rmed that these OVX rats had
al, 2009).
bone
loss,
undergone bone loss caused by estrogen de!ciency, with signi!cantly decreased BMD at the lumbar vertebrae 1–5 (LV,
osteocalcin
was
signi!cantly
(Figure 2. Scl-AbII treatment on area BMD at lumbar vertebrae and femur-tibia)
212%) and femur-tibia (29%) regions
Figure 2
compared
control
increases areal BMD at lumbar vertebrae
animals (Figures.2Aand2B). Scl-AbII was
and femur-tibia. BMD was measured in vivo
administered to OVX rats for 5weeks, at
by DXA at BL just before treatment and
with
sham-operated
show that Scl-AbII treatment
weekly there after at lumbar vertebrae (A)
of the three groups. Representative 3D
and femur-tibia (B).(Li et al, 2009).
images were selected based on the median trabecular bone volume (Tb.BV/TV) of each
In the same study, ÂľCT analysis of the
group. (B) Values for trabecular volumetric
metaphyseal region of the distal femur
BMD(Tb.vBMD). (C)Values for Tb.BV/TV.
con!rmed the expected trabecular bone loss
(Li et al, 2009)
caused by OVX and indicated that Scl-AbII treatment was able to increase trabecular thickness (Figure 3A). Quantitative analysis of the trabecular region showed that vehicletreated OVX rats had signi!cantly decreased vBMD(235%) and BV/TV(256%) compared with sham controls (Figure.3B). Trabecular number was signi!cantly decreased but trabecular thickness was unchanged after OVX. Five weeks of Scl-AbII treatment in OVX rats completely restored trabecular vBMD and BV/TV back to sham control levels through a signi!cant increase(+57%) in trabecular thickness and non signi!cant increase in trabecular number(+50%).(Li et al, 2009).
In another study, which is done by Ominsky et al (2011), 4 to 5 year-old male cynomolgus monkeys (mean body weight 6.4kg, range5.1 to 7.7kg) were assigned to receive either vehicle (n=21) or Scl-Ab (humanized Scl-Ab V, n=22) to investigate the effects of systemic administration of SclAb in increasing bone mass and bone strenght. Ten weeks of systemic Scl-Ab administration resulted in greater bone mass in
fractured
compared
fibulas
with
(p<.05;Fig.4A).
by
pQCT
when
vehicle-treated
controls
Threshold
analysis
demonstrated that there was a greater amount of mature callus area (+27%) and
(Figure 3. Scl-AbII treatment in osteopenic
BMC (+30%) in the Scl-Ab-treated group
rats)
than in the vehicle-treated group (both p<.05), as illustrated in black within the
Figure 3. show that Scl-AbII treatment in osteopenic rats restores trabecular BMD and bone volume back to sham levels at distal femur.(A)The distal femur region of analysis (top left panel) and representative 3D ÂľCT images of a 1-mm central section from each
representative pQCT images from each group. The increase in callus bone mass with Scl-Ab treatment was associated with improved bone strength, as demonstrated by a 48% increase in torsional stiffness (p<.05)
and a 32% increase in peak torque (p=.07)
SOST gene, is secreted by cystine-knot
compared with vehicle (Fig.4B, C).
glycoprotein expressed primarily in
(Figure 4 Scl-Ab on bone mass and callus strength in a non human primate fibular osteotomy model)
bone,
speci!cally
by
osteocytes.
Individu with sclerostin deficiency has high
bone
mass,
increased
bone
strength, and resistance to fracture.
Figure 4. show systemic administration of
Sclerostin works by inhibiting the Wnt
Scl-Ab increased the bone mass and strength
and
of the callus in a non human primate fibular
signaling pathways that are critical for
osteotomy model. (A) Quantification of area
osteoblast proliferation and activity. By
and
inhibiting sclerostin, this agent should
BMC
from
the
pQCT
scans
bone
morpho-genetic
demonstrated significant improvements in
enhance
total callus BMC, mature callus area, and
osteporosis treatment.
mature callus BMC with Scl-Ab treatment.
osteoblastic
2. Monoclonal
antibodies
protein
function
for
(mAbs)
are
(B)Torsional stiffness and (C) peak torque
produced by cell lines or clones
were increased in the Scl-Ab-treated fibular
obtained from animals that have been
osteotomies, as determined by destructive
immunized with a substance(s). Amino-
torsion testing.(Ominsky et al,2011).
terminal
and
sclerostin
peptides
homology
to
Conclusion 1. Osteoporosis is a progressive bone disease that is characterized by a decrease in bone mass and density which can lead to an increased risk of fracture. The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Sclerostin is de!ned its function as a key negative regulator of bone mass and bone formation. Sclerostin, encoded by the
carboxy-terminal with
limited
sclerostin
domain-
containing protein-1 were synthesized using f-moc chemistry. The peptides were conjugated to KLH and the conjugates were used for immunization of mice. Monoclonal antibodies were obtained
and
characterized
using
bacterially expressed and insect cellâ&#x20AC;&#x201C; expressed recombinant scl. The aminoterminal
(IgG
2aK)
and
carboxy-
terminal (IgG 2bK) antibodies bound bioactive sclerostin that was expressed
in an insect-cell expression system with
tmentsandsideeffects/treatmenttypes/
dissociation constants in the nanomolar
immunotherapy/cancer-
range. The antibodies are potentially
immunotherapy-pdf
useful agents that can be used for modulating sclerostin bioactivity. 3. Short term administration of Antisclerostin monoclonal antibody in an aged OVX rat model of postmenopausal osteoporosis
resulted
in
marked
2. Becker,
Carolyn
Sclerostin
B.
(2014).
Inhibition
for
Osteoporosis â&#x20AC;&#x201D; A New Approach. N ENGL J MED, Volume 370;5 : 476477 | DOI: 10.1056/NEJMe1315500
increases in bone formation, bone mass
3. Chen P, Satterwhite JH, Licata AA,
and bone strength. These changes were
Lewiecki EM, Sipos AA, Misurski
associated with signi!cant bone volume
DM, Wagman RB. (2005). Early
increases in cortical and trabecular
changes in biochemical markers of
bone.
bone
Inhibition
systemic
of
sclerostin
adminitration
sclerostin
of
monoclonal
by
Antiantibody
formation
response
to
predict
BMD
teriparatide
postmenopausal
women
in with
increased bone formation, bone mass,
osteoporosis. J Bone Miner Res
and bone strength in non-fractured
20(6):962-970
bones in non human primate models.! So this antibody-mediated blockade of sclerostin represents a promising new preventional approach for the anabolic prevention of people with high risk bone-related
disorders,such
as
postmenopausal osteoporosis.
4. Craig T A., Sommer S L., Beito T G. and Kumar R. (2009). Production and Characterization of Monoclonal Antibodies to Human Sclerostin. Hybridoma 28(5):
(Larchmt), 377â&#x20AC;&#x201C;381
Volume |
doi:
10.1089/hyb.2009.0036
References
5. Ezzat MK. Howell KG. Bahler CK. 1. American Cancer Society. (2014). Monoclonal
Antibodies
cancer.
Retrieved
to
Beito TG. Loewen N. Poeschla EM.
treat
Fautsch MP. Characterization of
from
monoclonal antibodies against the
http://www.cancer.org/treatment/trea
glaucoma-associated
protein
myocilin.
Exp
Eye
Res.
2008;87:376–384
S., Morony S., Gong J., Cao J., Gao
6. Fatmah. (2008). Osteoporosis dan Faktor Risikonya pada Lansia Etnis Jawa.
Media
Medika
Indonesia
Volume 43 Nomor 2. 7. Kosmin,
Dana
Osteoporosis.
10. Li X., Ominsky M S., Warmington K Y.,
Shalhoub
V.,
Tipton
B.,
Haldankar R., Chen Q., Winters A., Boone T., Geng Z., Niu Q T., Ke H Z., Kostenuik P J., Simonet W S., Lacey D L., and C Paszty. (2009).
Jacobs.
(2014).
Antibody
Treatment
from
Increases Bone Formation, Bone
http://emedicine.medscape.com/articl
Mass, and Bone Strength in a Rat
e/330598-overview#aw2aab6b2b2
Model
8. Lewiecki, Sclerostin
Retrieved
Sclerostin
Michael
E,
(2011).
: A Novel Target for
Intervention in the Treatment of Osteoporosis, New Mexico Clinical Research & Osteoporosis Center :
of
Post
menopausal
Osteoporosis. Journal Of Bone And Mineral
Research,
Number4
:
578
Volume24 -
588
|
doi:10.1359/JBMR.081206 11. Mayoclinic.
(2014).
Monoclonal
300 Oak St. NE, Albuquerque, New
antibody drugs for cancer. Retrieved
Mexico, 87106, United States
from
9. Li X, Ominsky MS, Niu QT, Sun N, Daugherty
B,
D’Agostin
D,
Kurahara C, Gao Y, Cao J, Gong J, Asuncion F, Barrero M, Warmington K, Dwyer D, Stolina M, Morony S,
http://www.mayoclinic.org/diseasesconditions/cancer/indepth/monoclonal-antibody/art20047808 12. Mayoclinic. (2014). Osteoporosis.
Sarosi I, Kostenuik PJ, Lacey DL,
Retrieved
Simonet WS, Ke HZ, Paszty C.
http://www.mayoclinic.org/diseases-
(2008). Targeted deletion of the
conditions/osteoporosis/basics/cause
sclerostin gene in mice results in
s/con-20019924
increased bone formation and bone strength. J Bone Miner Res 23:860– 869
from
13. McClung MR, San MJ, Miller PD, Civitelli R, Bandeira F, Omizo M, Donley DW, Dalsky GP, Eriksen EF.
(2005). Opposite bone remodeling
(2011). Inhibition of Sclerostin by
effects
Monoclonal
of
teriparatide
and
Antibody
Enhances
alendronate in increasing bone mass.
Bone Healing and Improves Bone
Arch Intern Med 165(15):1762-1768
Density
14. Moester MJ, Papapoulos SE, Löwik CW, et al. (2010). Sclerostin: current knowledge and future perspectives. Calcif Tissue Int ; 87 : 99 – 107 . 15. National Academy Press (1999). Monoclonal Antibody Production. Retrieved
from
http://grants.nih.gov/grants/policy/an tibodies.pdf
and
Strength
of
Non
fractured Bones. Journal of Bone and Mineral Research, Vol.26,No.5 : pp1012–1021
|
DOI:10.1002/jbmr.307 19. Ominsky M. S., Vlasseros F, Jolette J et al. (2010). Two doses of sclerostin antibody in cynomolgus monkeys increases bone formation, bone mineral density, and bone strength. J Bone Miner Res; 25 : 948
16. National Institutes of Health. (2014). Osteoporosis.
Retrieved
from
http://www.nlm.nih.gov/medlineplus /osteoporosis.html
– 59 20. Padhi D, Jang G, Stouch B, Fang L, Posvar
E.
(2011).
placebo-controlled,
Single-dose, randomized
17. Nelson A.L., Dhimolea E., and
study of AMG 785, a sclerostin
Reichert J.M. (2010). Development
monoclonal antibody. J Bone Miner
trends
Res 26(1):19-26
antibody
for
human
monoclonal
therapeutics.
Nature
Reviews Drug Discovery 9 : 767774| doi:10.1038/nrd3229 18. Ominsky M S., Li C., Li X., Tan H L., Lee E., Barrero M., Asuncion F J., Dwyer D., Han C Y., Vlasseros F., Samadfam R., Jolette J., Smith S Y., Stolina M., Lacey D L., Simonet W S., Paszty C., Li G dan Ke H Z.
21. Papapoulos, Socrates E. (2011). Targeting
sclerostin
treatment
of
as potential
osteoporosis.
Ann
Rheum Dis;70(1):119–122 22. Sawakami K, Robling AG, Ai M, Pitner ND, Liu D, Warden SJ, Li J, Maye P, Rowe DW, Duncan RL, Warman ML, Turner CH. (2006).
The
Wnt
is
Wilt E. Karperien M. Hamersma H.
skeletal
Papapoulos SE. ten Dijke P. Lowik
mechanotransduction but not for the
CW. Sclerostin is an osteocyte-
anabolic
to
expressed negative regulator of bone
parathyroid hormone treatment. J
formation, but not a classical BMP
Biol Chem 281:23698â&#x20AC;&#x201C;23711
antagonist.
essential
co-receptor
LRP5
for bone
response
23. van Bezooijen RL. Roelen BA. Visser A. van der Wee-Pals L. de
J
2004;199:805â&#x20AC;&#x201C;814.
Exp
Med.
Tables and figures
Figure 1
!
Figure 2
Figure 3
Figure 4
Table 1
LITERATIRE REVIEW Dementia in Elderly : The Incidence and Its Relation with Hyperglycemia Aninditya Verinda Putrinadia 1, Edbert Wielim 1, Yuanita Citra Syafitri1 1
Faculty of Medicine, Sebelas Maret University (AMSA-UNS) Abstract
Dementia is a progressive, degenerative condition that affects memory, thinking behaviour, emotion and day-to-day functioning. Dementia has the potential to have a devastating impact on the public health systemsof Asia Pacific countries. This is not only because of the .greying. of the population but because dementia is among the most disabling of all chronic diseases. Paper were identified by two search engine, pubmed and scholar google which reported the prevalence of dementia, hypertension, hyperglycemia, hyperlipidemia during December 2004 through December 2014. Paper selection processes were done bye author separately. Studies which met the eligible criteria were included in this review. Borderline hyperglycemia was associated withadjusted hazard ratios (95% CIs) of 1.67 (1.04–2.67) fordementia and 1.77 (1.06–2.97) for Alzheimer’s disease; thesigni!cant associations were present after additional adjustmentfor future development of hyperglycemia.: Hyperglycemia can increase risk factor of dementia. Keyword: Dementia, hyperglycemia.
Introduction
sector in most of these countries is usually
It is evident that dementia already has
miniscule and would be overwhelmed by the
dramatic effects on the lives of millions of
attendant needs for optimal health care
people across the region and on public
provision for the cases [3]. The right
health costs. There is no cure yet but much
approach at curtailing the imminent
can be done to improve the quality of life of
epidemic is to place emphasis on preventive
people with dementia and the families who
strategies against the modifiable risk factors.
care for them. Dementia is a progressive,
Hyperglycemia means high blood sugar or
degenerative condition that affects memory,
glucose, it is a condition in which the
thinking behaviour, emotion and day-to-day
amount of glucose in the blood plasma is
functioning.
raises than usual.1 Hyperglycemia is defined
Dementia has the potential to have a
as blood glucose >140 mg/dl, and treatment
devastating impact on the public health
is recommended when glucose levels are
systemsof Asia Pacific countries. This is not
persistently >140â&#x20AC;&#x201C;180 mg/dl. Ideally, blood
only because of the .greying. of the
glucose levels range from 90 to 130 mg/dL
population butbecause dementia is among
before meals, and below 180 mg/dL within 1
the most disabling of all chronic diseases.
to 2 hours after a meal. Body gets glucose
The .burden of disease. is measured by the
from most foods that consumed or produces
number of years of healthy life lost as a
the glucose in the liver and muscles using
consequence of a condition. It is the sum of
other chemicals. Glucose in the body will
the .mortality burden. (the years of life lost
enter the cells through the blood with energy
due to premature death) and the .disability
supply from insulin. Insulin is a hormone
burden. (the years of healthy life lost due to
made by the pancreas which the release is
[1]
disability)! .
influencedbythe levels ofsugarin the blood.
Dementia poses considerable public health
Insulin helps move glucose from digested
challenge in developing countries because of
food enter into cells. In diabetic patients,
the projected increase in the number of
glucose does not enter the cells sufficiently
affected individuals that would occur in
but just staying in the blood and creating
tandem with rapid ageing of the population
high blood sugar levels. If the cause is a
[2]
. The general fiscal allocation to the health
damage of pancreas so insulin can not be produced the diabetes category include in
type 1 diabetes, but if the insulin self does
especially pronounced in carriers of the
not work properly the category of diabetes is
APOE-4 gene. The relationship appears to
in type 2.2 Hyperglycemia have been
be synergistic, leading to a more than
demonstrated relatively consistently to be
fivefold increase in the risk for Alzheimerâ&#x20AC;&#x2122;s
risk factors for cognitive decline,3 mild
disease for subjects with diabetes and
cognitive
(MCI),4
impairment
and
APOE-4 compared with those without these
dementia.5 Several prospective studies have
two factors.12 The presence of multiple
found that the risk for developing dementia
cardiovascular
increases with the presence of obesity in
substantially increases the risk of late-life
middle age and diabetes in later life.
6-9
risk
factors
at
midlife
dementia in a dose dependent manner,13 and type 2 diabetes is associated with a twofold
Glucose is the main fuel of the brain, its
increased risk of vascular dementia.14
levels should be maintained within a narrow range to ensure normal brain function.
There are several mechanisms whereby
Indeed,
borderline hyperglycemia might in-uence
the
literature
shows
that
uncontrolled blood glucose levels will
the
impact
underlying
brain
structure
potentiating
cognitive
Hypeglycemia
which
and
function
impairment.
unrecognized
initiation
and
promotion
pathologies
of
associated
the with
dementia.15 First, increased blood glucose
or
may have direct harmful effects on vascular
inadequately treated for several years can
endothelium or atherosclerotic plaques.
damage multiple tissues in the brain, its
Glucose dysregulation may develop in a
etiology is probably multifactorial. Chronic
cluster of risk factors including obesity,
hyperglycemia promotes the development of
insulin resistance, atherogenic dyslipidemia,
cerebral microvascular disease and some
and hypertension. These factors constitute
research data show that there is influence
the metabolic syndrome, which are reported
from inflammatory mediators,10 oxidative
to be predictors of cerebrovascular disease,
11
ischemic stroke, and accelerated cognitive
hypothalamic-
decline and dementia.15-16,18 . Second, toxic
pituitary-adrenal axis dysregulation that
effects of higher blood glucose could lead to
roles in cognitive impairment and dementia
slowly progressive functional and structural
etiology.10 The effect of hyperglycemia is
abnormalities in the brain. Chronically
stress, +-amyloid deposition in the brain, rheological
factors,
and
hyperglycemic rodents have been found to
pathophysiology
express
dementia.
cognitive
impairments
and
of
hyperglycemia
and
Criteria that we used for this
abnormalities in synaptic plasticity .19 These
review are up to date paper (10 years before
processes could affect brain tissue directly
2014).
but can also lead to microvascular changes.
hyperglicemia happens, dementia happens
The glucose-mediated effects on cognition
and the relationship between hyperglycemia
and brain structure could be referred to as
and dementia. We also look the relation of
“accelerated
ageing”.14,20
brain
Third,
Look bye study pustaka how
hypertension and hyperlipidemia toward
glucose dysregulation may be linked to
dementia as confounding factors.
alterations in amyloid metabolism through
!
changes in insulin and its receptor in brain and through the formation of advanced
Result
glycation end products .21 Insulin appears to
Table 1 show that data are HRs (95% CIs)
stimulate amyloid-b by competing for
unless otherwise indicated. *HRs and 95%
insulin
CIs estimated with adjustment for age, sex,
degrading
hyperglycemia
is
enzyme.
The
accompanied
by
last, an
education,
follow-up
survival
status,
accelerated rate of advanced glycation end
baseline MMSE score, stroke, heart disease,
product (AGE) formation. AGEs have been
diastolic
demonstrated to accumulate in the neuritic
antihypertensive drug use and, if applicable,
plaques
of
for systolic blood pressure. **Twenty one
Alzheimer’s disease.22 AGEs also appear to
subjects for blood pressure readings had
accelerate amyloid aggregation through
missing values (Munch G et al, 2007).
and
neurofibrillary
tangles
blood
pressure,
and
cross-linking of extracellular proteins and may contribute to tau protein and tangle
We also look the relation of hypertension
formation and oxidative stress.23
and hyperlipidemia toward dementia as confounding factors.
Method For this review paper, we use two search engine. The first one is google scholar and the second is pubmed. Keyword that we use are
hyperglycemia,
dementia,
and
Table 2 show In ONTARGET, a 56 month median duration month followup found cognitive impairment occurred in 652 (8%) of the 7865 patients allocated ramipril, 584
(7%) of the 7797 allocated telmisartan, and
hypertensionsigni!cantly increased the risk
618
of dementia andAlzheimer’s disease (Table
(8%)
of
the
7807
combination of the two.
allocated
a
Corresponding
1).
The
adjusted
HRs
related
tothe
figures for cognitive decline were 1314
interaction term of borderline hyperglycemia
(17%), 1279 (17%), and 1240 (17%),
by severesystolic hypertension were 3.77
respectively.
(95% CI 0.84 –16.91; P =0.08) for dementia and
Discussion
4.89
(1.07–22.42;
P
=
0.04)
forAlzheimer’s disease.
Weili Xu et al, 2007 were analyzed the
TABLE 1. Adjusted HR of dementia and
relationship
and
Alzheimer’s disease for the combined effect
Cox
of borderline hyperglycemia and blood
between
hyperglycemia
dementia using
proportionalhazards models. During the 9year
follow-up,
397subjects
pressure.24
developed
dementia, including 307 Alzheimer’scases.
Borderline hyperglycemia appeared to have
At baseline, 47 subjects were identi!ed with
a multiplicative effect with severe systolic
borderlinehyperglycemia and they had a
hypertension (.180 mmHg) on the risk of
higher incidence rate of dementia and
Alzheimer’s disease, which is in line with
Alzheimer’s
Borderline
the previous !ndings)26,27 that comorbid
hyperglycemia was associated withadjusted
hyperglycemia or type 2 diabetes and
hazard ratios (95% CIs) of 1.67 (1.04–2.67)
hypertension exacerbated cognitive decline
fordementia
for
and had a much higher risk of developing
thesigni!cant
Alzheimer’s disease.The natural history of
disease.
and
Alzheimer’s
1.77
disease;
(1.06–2.97)
associations were present after additional
hyperglycemia
adjustmentfor
glucose regulation, which may last for
future
development
of
hyperglycemia. 24
is
preceded
byimpaired
yearsbefore it is clinically manifested.28The data above showedthat during 9 years of
Qiu C et al, 2003 examined the joint effect
follow-up, the incidence of diabetesin
of
andsevere
subjects with borderline hyperglycemia is
systolic hypertension (. 180 mmHg).25
much higher than inindividuals without the
Borderline hyperglycemia in combination
condition.
with
borderline
hyperglycemia
severe
systolic
Clinical and cross-sectionalstudies have
hippocampal
suggested that impaired glucose regulationis
streptozotocin-induced
related
Diabetes,45, 1259 –1266.
to
performance.
a 29-31
decrease
cognitive
prospective
plasticity diabetic
in rats.
study
3. Biessels GJ, Staekenborg S, Brunner E,
showed that pre-diabetesincreased the risk
Brayne C, and Scheltens P. (2006). Risk
of
impairment
of dementia in diabetes mellitus: A
inelderly women.32 We found that borderline
systematic review. Lancet Neurol,5, 64
hyperglycemia was associated with an ~70%
–74.
developing
A
in
synaptic
cognitive
increased risk of developingdementia and
4. Cardoso S, Correia SC, Santos RX,
Alzheimer’s disease after controlling for
Carvalho C, Candeias E, Duarte AI et
major potential confounders. Hyperglycemia
al.
was previouslyfound to be associated with
hypoglycemia and dementia: Role of
an increased risk of subsequentdementia and
mitochondria and uncoupling proteins.
vascular dementia, independently ofother
Current
vascular disease, and marginally with
(4),586-601.
Alzheimer’sdisease in this population.
(2013).
Hyperglycemia,
Molecular
Medicine,
13
5. Convit A, Wolf OT, Tarshish C, and de Leon MJ. (2004). Reduced glucose
Conclusion
tolerance
is
associated
with
poor
Hyperglycemia can increase risk factor of
memory performance and hippocampal
dementia.
atrophy among normal elderly. Proc Natl Acad Sc U S A, 100, 2019-2022. 6. Dickson DW, Sinicropi S, Yen SH, Ko
References
LW, Mattiace LA, Bucala R et al.
1. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, and Bennett DA. (2004). Diabetes mellitus and risk of alzheimer disease
and
decline
in
cognitive
function.Arch Neurol, 61, 661-666. 2. Biessels GJ, Kamal A, Ramakers GM, Urban IJ, Spruijt BM, Erkelens DW et al.
(2006).
Place
learning
and
(2006).
Glycation
and
microglial
reaction in lesions of Alzheimer’s disease. Neurobiol Aging, 17, 733. 7. Ferry R. (2014). High blood sugar (hyperglycemia)
overview.Retrieved
from http://www.emedicinehealth.com/high_ blood_sugar_hyperglycemia/article_em.
htm#high_blood_sugar_hyperglycemia_ overview – December 2014. 8. Gustafson D, Rothenberg E, Blennow
13. Launer LJ. (2005). Diabetes and brain aging: Epidemiologic evidence. Curr Diab Rep,5, 59 –63.
K, Steen B, and Skoog I. (2004). An 18-
14. Magaji V and Johnston JM. (2011).
year follow-up of overweightand risk of
Inpatient management of hyperglycemia
Alzheimerdisease. Arch Intern Med,
and diabetes. Clinical Diabetes, 29 (1),
163, 1524-1528.
3-9.
9. Haan MN. (2006). Therapy insight:
15. Mayeda ER et al. (2013). Chronic
Type 2 diabetes mellitus and the risk of
hyperglycemia and 10-year risk of
late-onsetalzheimer’s disease. Nat Clin
dementia and cognitive impairment
Pract Neurol, 2, 159.
among
10. Hassing LB, Hofer SM, Nilsson SE,
older
Diabetes
Mexican
Care,
36,
Berg S, Pedersen NL, McClearn Get al.
Retrieved
(2004). Comorbid type 2 diabetes
care.diabetesjournals.org.
mellitus and hypertension exacerbates
Americans. 2600-2606. from
16. MedlinePlus. (2014). Hyperglycemia.
cognitive decline: evidence from a
Retrieved
from
longitudinal study. Age Ageing,33, 355–
http://www.nlm.nih.gov/medlineplus/hy
361.
perglycemia.html - December 2014.
11. Hassing LB, Johansson B, Nilsson SE,
17. Munch G, Mayer S, Michaelis J,
Berg S, Pedersen NL, and Gatz M.
HipkissAR, Riederer P, Muller Ret al.
(2004). McClearn G: Diabetes mellitus
(2007).
is a risk factor for vascular dementia,
glycationend-products
but not for alzheimer’s disease: a
inhibitorson
nucleation-
population-based study of the oldest
dependentpolymerization
of
old. Int Psychogeriatr,14, 239–248.
amyloidpeptide.Biochem Biophys Acta,
12. Kernan WN, Inzucchi SE, Viscoli CM,
Influence
of
advanced
and
AGEbeta-
1360, 17-29.
Brass LM, Bravata DM, and Horwitz
18. Peila R, Rodriguez BL, and Launer LJ.
RI. (2004). Insulin resistance and risk
(2004). Honolulu-Asia aging study:
for stroke. Neurology,59:809 –815.
Type 2 diabetes, APOE gene, and the risk
for
dementia
and
related
pathologies: The Honolulu-Asia Aging
alzheimer’s
disease.
Study. Diabetes, 51: 1256-1261.
Neurosci,18, 172–176.
Trends
19. Qiu C, von Strauss E, Fastbom J,
24. Sokal J, Messias E, Dickerson FB,
Winblad B, and Fratiglioni L. (2004).
Kreyenbuhl J, Brown CH, and Goldberg
Low
of
RW. (2004). Dixon LB: Comorbidity of
dementia in the Kungsholmen project:
medical illnesses among adults with
A
serious mental illness who are receiving
blood 6-year
pressure follow-up
and
risk
study.
Arch
Neurol,60, 223–228.
community psychiatric services. J Nerv
20. Ravona-Springer R, Luo X, Schmeidler J, Wysocki M, Lesser G, Rapp Met al.
Ment Dis, 192, 421-427. 25. Strachan MW. (2011). The brain as a
(2010). Diabetes is associated with
target
increased rate of cognitive decline in
Exploring the links with cognitive
questionably demented elderly. Dement
impairment and dementia. Diabet Med,
Geriatr
28, 141–147.
Cogn
Disord,
29,
68–74.
PubMed: 20130405.
organ
in
type
2
diabetes:
26. Uusitupa MI. (2006). Early lifestyle
21. Roberts RO, Geda YE, Knopman DS,
intervention in patients with non-
Christianson TJ, Pankratz VS, Boeve
insulindependentdiabetes mellitus and
BFet al. (2008). Association of duration
impaired
and severity of diabetes mellitus with
Med,28, 445– 449.
mild
cognitive
Neurol,
65,
impairment.
1066–1073.
glucose
tolerance.
Ann
Arch
27. Weili Xu et al.(2007).The effect of
PubMed:
borderline diabetes on the risk of
18695056.
dementia
22. Schnaider BM, Goldbourt U, Silverman
and
alzheimer’s
disease.
Diabetes, 56.
JM, Noy S, Schmeidler J, Ravona-
28. Whitmer RA, Sidney S, Selby J,
Springer Ret al. (2004). Diabetes
Johnston SC, and Yaffe K.(2005).
mellitus in midlife and the risk of
Midlife cardiovascular risk factors and
dementia
risk of dementia in late life. Neurology,
three
decades
later.
Neurology, 63, 1902–1907. PubMed: 15557509.
64, 277-281. 29. Whitmer RA, Gunderson EA, Barrett-
23. Smith MA, Sayre LM, Monnier VM,
Connor E, Quesenberry CP Jr, and
and Perry G. (2005). Radical ageing in
Yaffe K. (2005). Obesity in middle age
and future risk of dementia: A 27 year
32. Yaffe K, Kanaya A, Lindquist K,
longitudinal population based study.
Simonsick EM, Harris T, Shorr RI et al.
BMJ,330, 1360.
(2004).
30. Xu WL, Qiu CX, Wahlin A, Winblad B, and Fratiglioni L. (2004). Diabetes mellitus and risk of dementia in the Kungsholmen project: A 6-year followup study. Neurology,63, 1181–1186. 31. Yaffe K, Blackwell T, Kanaya AM, Davidowitz N, Barrett-Connor E, and Krueger K. (2004). Diabetes, impaired fasting glucose, and development of cognitive impairment in older women. Neurology,63, 658 –663.
The
metabolic
syndrome,
in-ammation, and risk of cognitive decline. JAMA,292, 2237–2242.
Tables and figures
Joint exposure Borderline status
At risk (n)
Dementia*
hyperglycemia
Alzheimerâ&#x20AC;&#x2122;s disease*
Systolic blood pressure (mmHg)** < 180
No
899
1.00 (Ref.)
1.00 (Ref.)
< 180
Yes
38
1.54 (0.93-2.58)
1.63 (0.94-2.82)
# 180
No
207
1.00 (0.74-1.34)
0.98 (0.70-1.38)
# 180
Yes
8
4.41 (1.08-17.99)
6.27 (1.53-25.80)
Table 1. Sample of Hyperglycemia ! &'()*+,-*'+!./0121! 0,(*30*$! -/$(*1,0-,+!./0121! 0,(*30*$!
""! $%&'!(!&'!)!
#$! $%*'!+!,%$-!
%! $%.&!
$%&!
$%*!+!,%$,!
$%$/!
Table 2. Sample of Hypertension Corresponding figures for cognitive decline were 1314 (17%), 1279 (17%), and 1240 (17%), respectively
! -/$(*1,0-,+!./0121! 0,(*30*$! &'()*+,-*'+!./0121! 0,(*30*$!
4"! $%&-!
#$! $%*&!+!,%$/!
%! $%'.!
$%&'!
$%**!+!,%$0!
$%1*!
! 5+'-6/0!&0'117 1/&-*'+,$!1-289!':!;<<=! /$8/0$9!12)>/&-1! 16'?/8!-6,-! 8/&0/,1/8!@#!6,8!,+! *+./01/!,11'&*,-*'+!
""! ! ! ! ! ,%/!(!&')!
#$! ! ! ! ! ,%$!+!1%-!
%! !
?*-6!-6/!*+&*8/+&/!':! 5AB!*+8/3/+8/+-!':! 53'C!D/+'-93/! @6/!-60//!#*-9!E-289B!,! 3'32$,-*'+7),1/8! &'6'0-!':!=BF=<! 12)>/&-1!1/$/&-/8!:0'(! /$/&-'0,$!0'$$1B!16'?/8! -6,-!6*D6/0!@#!GHIJFK! (('$LMN!?,1! ,11'&*,-/8!?*-6! *+&0/,1/8!'881!':! 8/(/+-*,!)2-!+'-!5A!
!
Table 3. Sample of Hyperlipidemia
!
! ! ! ! $%$-!
LITERATIRE REVIEW The Role of Medical Student to Reduce the Number of Blindness in Eldery Nadya Eunice Sumolang 1 1
Faculty of Medicine, Hassanudin University(AMSA-Unhas)
Abstract Instead of their small seizes compared to others organs,eyes have a very much function for us. According to the data from the World Health Organization (WHO), there is 45 million peoples with visually impaired in the world and 80% among them is people with age above 50 years old. One of the type of cataracts which caused the biggest number of blindess in the world is senile cataract. Senile cataract is an affection of advance life and is essentially an ageing process.! This is very unfortunate because it could have been prevented through early detection (screening test) and surgical intervention.This paper is based on the study of literature obtained from websites worldwide, journals, articles, and textbooks are also related to the prevalence of senile cataract cataracts, especially in the elderly. The literature related to risk factors and knowledge related to senile cataract is also used in writing this paper.Basically, cataract is an eye disease that has a close relationship with the Elderly. Because of that, the increasing of life expectancy will affect the increasing prevalence of cataracts. The causes of senile cataract heretofore not known for sure. Several studies have helped to identify risk factors for the development of knowledge about senile cataract. The assortment of things that affect including environmental conditions, systemic diseases, diet, and age. Meanwhile, to prevent blindness in patients with senile Cataract is the early detection and cataract surgeryAs Medical Student, there are things that we can do to reduce the number of senile cataract sufferer. Which is to make a charity that provide socialization of risk factors senile cataract as well as raising funds for free cataract surgery. Keywords: cataract, senile, blindness, geriatry
Introduction Eyes are small organ, but they have a very much function for us. Eyes support many of
is very complex, yet it has many more functions of eyes than those mentioned above.
our activities. For example, while eating, we
According to the data from the World
need our eyes to see the food we are going
Health Organization (WHO), there are 45
to eat. We need our eyes so we can put the
million peoples with visually impaired in the
spoon into our mouth appropriately. Or
world and 80% among them are people with
while walking, we need our eyes to see the
age above 50 years old. And in Indonesia,
street in front of us so that we will not get
Badan Pusat Statistik Indonesia (BPSI) in
lost or even hit someone else. Eyes are also
2008 recorded that the number of people
needed to save us from anything which can
with visual impaired reached 4,5 million
block our way. And while combing –
peoples or about 1,5% of Indonesian
especially for woman – how can we know
population. Of that number, 76% among
that our hair has been neated if we didn’t see
them (about 2,6 million peoples) are
it with our eyes? How can we cook if we do
cataracts.
not have eyes? How can we read or watching TV if we do not have eyes? The presence of Braille’s Alphabetic may help
Cataract is a derivate from katarrhakies in
people with visually impaired to read, but it
Greek and known as cataracta in Latin
does not as comfortable as using our own
which means waterfall. This is caused due to
eyes. It also have many aspect that are being
the vision cataract sufferers like waterfalls
required when using Braille’s Alphabetic.
covered due to the cloudy lens. Cataract is
Bunga, in her journal with tittle “The
any opacity of the lens of the eye or of its
influence of Braille letters puzzle media
capsule. It maybe inherited or may occur at,
towards alphabet identification at blind
or soon after, birth (development cataract). It
kindergarten child in YPAB Tegalsari
most commonly arises, however, as a result
Surabaya” stated that there are many things
of degenerative changes associated with
which need to be managed for lean Braille’s
ageing
Alphabetic, they are: control of directions,
possible causes include diabetes mellitus,
sensitivity of palpability, font identification
drug administration (e.g. corticosteroids),
techniques, and searching row capability. It
(degenerative
cataract).
Other
galactosemia, ionising radiation, iritis, and
introduce the medical students about senile
trauma.
cataract so they can be better to understand their role in reduce the number of blindness in Elderly.
One of the type of cataracts which is being the causes with the biggest number of blindess in the world is senile cataract. Senile cataract is an affection of advance life and is essentially an ageing process. Sometimes there appears to be a familial tendency to cataract in which case the condition may develop at an earlier age in successive generations and phenomenon is known as anticipation and as a rule is usually bilateral but develops earlier in one eye than the other. Usually some degree of cataract is present after the age of 50 years and it equally affects both the sexes. In senile
cataract
gradually
and
the the
visions
decreased
lens
thickened
progressively. This is very unfortunate because it could have been prevented through early detection (screening test) and surgical intervention.
Methods This paper is based on the study of literature obtained from websites worldwide, journals, articles, and textbooks which related to the prevalence of senile cataracts, especially in the elderly. The literature that related to risk factors and knowledge of senile cataract are also being used in this paper. Results In the United States, at least 300.000 â&#x20AC;&#x201C; 400.000 peoples have impaired vision because of cataracts, with the complications of modern surgical techniques has produced 7000 cases of irreversible blindness. In Framing Eye researches, in 1973 - 1975 found that senile cataract sufferers are as much as 15.5% of 2477 patients were checked.
As medical students, we certainly have a high sense of empathy. We certainly do not want more and more people suffer senile cataract in their old age life. Therefore, this scientist paper is made with the purpose to
Discussion A. Epidemiology Basically, cataract is an eye disease
that
has
a
close
relationship with the Elderly.
Because of that, the increasing of
to different types of cataract.
life expectancy will affect the
Furthermore, they said that the
increasing
posterior
prevalence
of
subcapsular
cataract
cataracts. In figure III, we can
and cortical cataract are closely
see
cataract
linked to environmental stress
sufferers with age 50-69 years
such as exposure to ultraviolet
old compared to 70 years old and
light, diabetes, and medications
over because the number of life
which is consumed. However
expectancy of elderly at these
nuclear cataract seen have a
age are higher than in the age of
correlation
70 years old and over. And it also
Alcohol is related with all types
showed in figure IV. Not just
of cataracts.
that
so
many
that, from the figure IV we can
with
Similar
smoking.
analysis
is
see that the most causes of
complemented by Miglior et al.
cataract is senile cataract or
They found that cortical cataracts
cataract that occurs because of
related with diabetes over 5 years
aging.
and increased serum levels of
B. Etiology
potassium and sodium. A history
The causes of senile cataract
of
surgery
with
general
heretofore not known for sure.
anesthesia and the use of sedative
Several studies have helped to
drugs are related with a reduced
identify risk factors for the
risk of cortical cataract. Posterior
development of knowledge about
subcapsular cataract linked with
senile cataract. The assortment of
steroid use and diabetes, and
things
nuclear
that
environmental
affect
including conditions,
systemic diseases, diet, and age.
meaningful
multifactorial
disease
with
varying risk factors which related
have
relationship
a with
calcitonin and milk intake.
West and Valmadrid stated that the age-related cataract is a
cataracts
So, the risk factor are: â&#x20AC;˘
Systemic Diseases 2
Senile with
cataract many
related systemic
diseases,
including
cataract
cholelithiasis,
allergies,
described as a hypothesis
pneumonia,
coronary
that explains that senile cataract,
insufficiency,
opacity of the cortex,
hypotension,
probably caused by the mental
Systemic has
the lens. 2
hypertension
been
found
Al-Ghadyan and Cotlier
significantly increase the
documented an increase
risk
in temperature. In the
of
posterior
subcapsular cataracts.
posterior part of the lens
Another pathway were
in rabbits after exposed to
possible on the way from
sunlight
hypertension
temperature effects on the
and in
cornea
senile 2
structure of the protein in the
due and
to
increased
body temperature.
cataract is a change in the
In relevant studies, people
lens
capsule.
were reside in area which
Furthermore,
causing
much
changes
in
exposed
to
membrane
ultraviolet rays is more
and
likely to develop senile
permeability to ions and
cataract and faster than
ultimately will increase
those who reside in a
the
slightly
transport
intra-ocular
cause
deformation of cataracts. Ultraviolet Rays 2
In animal experiments by
to
glaucoma
â&#x20AC;˘
especially
effects of temperature on
retardation, and diabetes.
2
been
disease and heart disease
hypertension, 2
has
The
of
to
ultraviolet rays. â&#x20AC;˘
relationship
exposed
Another risk factors: 2
Another
thing
who
ultraviolet rays and the
significantly
development
with senile cataract is the
of
senile
associated
ages,
2
female
gender,
(behind the iris) with duty to
social class, and myopia.
focus the light to form a sharp
Workers who are exposed
shadow on the retina. The retina
to infrared radiation also
works like the film in a camera
have a high incidence of
that serves to record the shape of
the development of senile
the shadow of an object in the
cataract.
form of images. Images are
Although myopia is a risk
conducted
factor, it has been seen
nerve to the brain to be translated
that people with myopia
into something that we see.
through
the
optic
eye
Eyepiece has a section called
glasses will be extracted
wrapping the lens or the lens
at least 20 years older
capsule, the lens cortex which is
than emetrop cataracts.
located between the core nucleus
Indirectly
of the lens or lenses and lens
who
have
used
there
is
a
protective effect of the
capsule.
glass
adolescents,
eye
to
solar
ultraviolet radiation.
In
children the
and
nucleus
is
flabby, while the parent nucleus
Candigarh,
becomes hard. Cataracts can start
Correlates of Cataract in Elderly
from the nucleus, cortex, and
(figure I) also showed that 81.5%
subkapsularis lens.
Study
in
UT
of people with diabetes is also a
Pathophysiology
of
senile
cataract sufferers. And 73.9% of
cataract is complex and not yet
smokers also a cataract sufferers.
fully understood. At all events
Then, 73.7% alcohol addicts also
pathogenesis
a cataract sufferers. As well, 74%
involving complex interactions
of patients with hypertension is
between a wide - range of
also a cataract sufferers.
physiological processes. As an
C. Patofisiologi
is
multifactorial
old lens, the thickness and weight
Our eyes work like a camera.
gain while the accommodation
Eye lens located inside the eye
power is reduced. There is a new
cortical
layer
on
concentric
seen as more dense reaction even
pattern, the nucleus will be
fundus
depressed and hardened amid the
disappear altogether.
so-called nuclear sclerosis. Multiple
lens
Senile
opacities
cataract
may
can
be
mechanisms
classified into three main types:
affecting the progressive loss of
nuclear cataract, cortical cataract,
lens
and
transparency.
Lens
epithelium has changed most notably a decrease in the density
posterior
subcapsular
cataracts. D. Stage of Senile Cataract
changes in the age of the lens
Stage of senile cataract can
epithelial cells and the addition
be explained as below:
of a different lens fiber cells.
2
Progressive
oxidation
Incipient cataract; At this stage opacities ranging from
damage of old lenses developed
equatorial
into senile cataract. Some studies
shaped towards the anterior
show an increase in the product
and posterior cortex (cortical
of the oxidation and reduction of
cataracts).
anti-oxidant
subcapsular cataracts, which
vitamins
reduction
of
superoxide
dismutase.
important
for
the the
and enzyme It
seen
edge
serration
Posterior
anterior
subcapsular
is
opacities ranging posterior, a
oxidation
gap is formed between the
process in the formation of
lens
cataracts.
network
Lens opacities resulting lens
and
cortical contains
degenerative
tissue
fiber a (body
is not transparent so that the
Morgagni)
pupils
cataract. This turbidity can
are
white
and
gray.
on
Incipient
Opacities can also be found in a
cause
variety of localization in the lens
refractive index is not the
cortex and nucleus like. Fundus
same in all parts of the lens.
oculi
This form is sometimes settle
becomes
increasingly
difficult to be seen as more's hard
poliopia
therefore
2
for a long time. Examination
osmotic
shadow negative test.
degenerative lens material. In
Intumesen opacities
cataract; accompanied
Lens
circumstances mencembung
by
lenses will be able to create
swelling of the lens due to
barriers
degenerative lenses absorb
secondary
water. Water seeps into the
Examination shadow positive
gap resulting lens becomes
test.
swollen and large lens who
2
pupils
causing glaucoma.
Mature cataracts; In mature
will push the iris so that the
cataract, opacities has about
chamber becomes shallow
the entire mass of the lens.
than with the normal state.
Opacities
Pencembungan this lens will
deposits of Ca ions thorough.
be able to give complications
Liquid lens so that the lens
of
Cataracts
will exit back to the normal
cataract
size. Will occur if the lens
glaucoma.
usually
occur
in
is
caused
opacities
and lead to myopia lentikuler.
will lead to calcification of
In this state of hydration can
the lens. Anterior chamber
occur until the lens cortex
will return to normal size.
will mencembung and bias
Examination
power will increase, thus
negative test.
lamp
examination
seen
2
throughout
by
intumesen running quickly
providing miopisasi. On slit
2
pressure
long
shadow
Hypermature cataracts; This stadium has undergone a
vacuoles on the lens with the
process
lens fiber lamellae stretch
degeneration, can be hard or
distance.
soft
Immature cataracts; Opacities
degenerates lens out of the
is not about the entire lens
lens capsule so that the lens
coating.
volume
becomes smaller, yellow and
increase due to increased
dry. On examination with the
Lens
of and
melt.
further Mass
slit lamp seen in the chamber
the
and the presence of the lens
resulting in a decrease in
capsule
visual acuity.
folds.
When
the
process is accompanied by progressive capsule,
cataract
the
thick
rays
enter
into,
2. Often Feel Dazzled
lens
Sight to read felt
liquid
dazzled when lighting is
cortex degenerate and can not
too
get out, then it will show the
surferrers
cortex forms such as milk
pleased to read in places
bag
with
accompanied
by
a
strong,
so
the
often
low
feel
lighting.
nucleus are immersed in the
Besides, sight becomes
cortex of the lens because it
brighter at dusk than at
is heavier. This condition is
noon.
referred
to
as
cataract
Morgagni.
3. Seeing The Black Spots In A Field View of the
E. The Symptomps
Specific Eyes Positions
The signs of senile cataract are:
These usually
1. The Decreasing of Visual Acuity
complaints occur
beginning
at
the stage
(incipient). Patients will
When
cataracts
complain
slowly
occur at the edges of the
unobstructed sight as a
eye lens, the visual acuity
smokescreen that grew
will not change, but if the
thicker. When cataracts
location is in the middle
develop the sight would
of lens opacities, the sight
like smoky, foggy, even
will
to
just like seeing light at
with
the
the back of the thick fog.
of
light
not
interfere distribution
be
able
entering the retina is more real. Cataracts will block
4. Complaining of Diplopia atau Poliopia
So, the patient saw an
preventive measures to prevent
object double or multiple.
the occurrence of senile cataract.
This early sign of felt see
One of them are way with the
the lights or the moon
socialization
which much when you
especially for people which are
see with one eye closed.
very close to the risk factors,
This occurs because of
they are:
refraction
2
(refraction)
who irregular from the eye lens. 5. Myopia
this
disease,
Peoples who strated to being old
2
Diabetes Mellitus sufferers
2
People who mostly exposed
Due to the occurrence
by UV rays because of their
of cataract, lens absorbs the fluid so that becomes
of
works 2
Amiodarone, Chlorpromazinc
convex lens and the eye
(sedative),
kortikostcroid,
refractive
power
lovastatin,
phcnytoin
increased,
resulting
(antiseizure,
shadows will fall in front of
the
retina.
Early
treatment) consumer. 2
cataract patients will feel happy to see close does
epilepsy
Individuals which smoked 20 cigarettes or more a day
2
People
with
lactosa
or
not need glasses anymore.
galactosa
dietary,
low
But would have difficulty
riboflavin,
triptofan,
and
seeing far because of the
another amino acid dietary.
eye occur mioposasi on.
Giving education about diet
F. Senile Cataract and Blindness Preventive As we know, senile cataract is a type of cataract which very might be suffered by the Elderly. However, we can do some
high in vitamin C, E, and carotene antioxidant effect can be used to reduce the risk of cataracts due to the influence of free radicals.
Meanwhile, to prevent blindness in patients
let us try to further expand charity which
with senile Cataract is the early detection
provide socialization of risk factors senile
and cataract surgery. The last few years
cataract as well as raising funds for free
various operating techniques have been
cataract surgery.
developed from the writings of the ancient techniques
to
the
latest
techniques
fakoemulsi. Based on the integrity of the
No one wants their old age life filled with
posterior lens capsule, two main types of
darkness.
surgery
catarak
development of their offspring in the rest of
extraction (ICCE) and extracapsular cataract
their life. Everyone wants to see the beauty
extraction (ECCE).
of the world until the their time is in the end.
are
intracapsular
lens
Everyone
want
to
see
the
And, we can give it to the them, the
Conclusion
brightest life.
No body wants to be blind. But, cataract (especially senile cataract) follows people
References
with age. Senile Cataract is an eye disease
1. Agarwal, S., Agarwal, A., Apple,
that occurs at age 50 years or older. People
D. J., Buratto, L., Alio, J. L., &
suffering from senile cataract may develop
Agarwal, A. (2002). Textbook of
blindness if left unchecked. If blindness
OPHTHALMOLOGY.
occurs, the patient will have a decrease in
Delhi: Jitendar P Vij.
quality of life. Family and those closest to unavoidably would have be weighted. Sufferers
can
feel
useless
and
may
accelerate the time of death.
New
2. Bunga, S. (2014). Pengaruh Media
Puzzle
Huruf
Braille
Terhadap Pengenalan Abjad Pada Anak Tunanetra. Jurnal Pendidikan Khusus.
As Medical Student, we can reduce the
3. Harman, R. J., & Mason, P.
number of sufferer. We often held a charity
(2002).
as a form of our empathy to the society.
Healthcare.
Usually the charity is performed with of
Pharmaceutical Press.
blood pressure or mass circumcision. Now,
Handbook
of
Pharmacy Grayslake:
4. Maulana, d. R. (2015, January 2).
7.
dr. Razi. Retrieved from wordpress:
Healthly Eyes Without Glasses and
http://razimaulana.wordpress.com
Health Without Drugs. Kansas City.
5. Pujiyanto, T. I. (2004). Faktor-
8. Sehat Selalu. (2015, January 3).
Faktor Risisko yang Berpengaruh
Retrieved
Terhadap Kejadian Katarak Senilis.
http//www.sehatselalu.com
PhD Thesis, Universitas Diponegoro, Magister Epidemiologi, Semarang. Retrieved January 3, 2015
Richardson,
from
D.
R.
Sehat
(1940).
Selalu:
9. Sharma, M., Kumar, D., Mangat, C.,
&
Bhatia,
Epidemiological
(2008). Studay
of
Correlates
Wormald, R. (2013). The British
Elderly Population Aged Over 65
Asian
Years
Eye
Study:
In
Ut,
Cataract
An
6. Rauf, A., Malik, R., Bunce, C., & Community
Of
V.
Among
Chandigarh.
The
Outline of results on the prevelance
Internet Journal of Geriatrics and
of eye disease in British Asians with
Gerontology.
origins from the Indian subcontinent. Indian Journal Ophthalmol, 61:53-8.
10. Tana, L. (2004). Faktor Resiko dan Upaya Pencegahan Katarak Pada Kelompok Kerja. INFORMASI.
? Video
Look At Me !""#$%&&'''()*+"+,-(.*/&'0".!123'!-45'6-789:
Give, Love, And Serve !""#$%&&'''()*+"+,-(.*/&'0".!123;<=>/?'@@=A:
Diabetes In Elderly, Youth Responsibility !""#$%&&'''()*+"+,-(.*/&'0".!123@!BCD.EFG,H:
Share Your Warmth, Keep The Elders Healthy !""#$%&&'''()*+"+,-(.*/&'0".!12367I/*J-A5B':
Geriatric Activities To Fight The Degenerative Disease !""#$%&&'''()*+"+,-(.*/&'0".!123*KLMNDOPQ#9:
Save Elderly From Danger !""#$%&&'''()*+"+,-(.*/&'0".!123RR#DST@A*BL:
ABC Power For Elder !""#$%&&'''()*+"+,-(.*/&'0".!123UP#L"*V)LU*:
Golden Age, Move The Golden Body !""#$%&&'''()*+"+,-(.*/&'0".!123+"U5N2=R.HC:
Geriatric Disease : Osteoporosis !""#$%&&'''()*+"+,-(.*/&'0".!123=WXJD?YZ9PH:
Osteoporosis !""#$%&&'''()*+"+,-(.*/&'0".!1232V)Z[\R<RC.: :
? Scientific Poster
ROBOTICS EXOSKELETON FOR PHYSICAL REHABILITATION IN DISABLED POST- STROKE GERIATRIC PATIENT Cindy Kahono, Sallie Naomi Atma Jaya Catholic University of Indonesia
Synopsis: Stroke is an age related-disease. As the number of geriatric population and their life expectancy increase, therefore the stroke probability will also increases. From the current method of health care, the mortality number caused by stroke might decrease but the patient disability post-stroke still occurred. To obtain optimum recovery, intensive, and focus rehabilitation is needed. Due to this fact, the 21st century has currently offered robotics exoskeleton as a new method of rehabilitation for disabled post stroke patient that can fulfill the current needs in health care. Conducted via systematic review, the study obtained proof of robotic exoskeleton to be used as a physical rehabilitation in upper limb and lower limb, and the safety test of this product on disabled post stroke geriatric patient. The study conducted showing result that robotic exoskeleton in physical rehabilitation is acceptable to be used as a rehabilitation property (algorithms program success), cause a significant motoric improvement in patients (improvement in Jerk, strength, velocity, and motoric assessment chart), and also safely (no adverse effect occurred) used. And thus it is concluded that robotic exoskeleton is more effective as a rehabilitation method compared to the current conventional rehabilitation method and it is also safe to be used as a rehabilitation property in disabled post-stroke geriatric patients. Keywords: geriatric, robotic exoskeleton, post-stroke, physical rehabilitation
GENISTEIN IN TEMPEH AS POTENTIAL SUBSTANCE IN PREVENTING NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION Ayudhea Tannika, Budiman Atmaja, Giovanni Reynaldo, Sri Handawati Wijaya University of Kristen Krida Wacana
Synopsis: Age-Related Macular Degeneration (AMD) is the leading cause of severe vision loss in persons over age 50. Indonesia has the highest prevalence of AMD compared with other countries in South-east Asia. Unfortunately, current AMD management methods offered requires a lot of funds. Besides, several problems have been noticed during the clinical development of angiogenesis inhibitors. With the idea that progression of AMD is associated with the angiogenic trait of retinal micro vascular, the authors suggest the use of a substance in tempeh called
genistein as a potential angiogenesis inhibitor. This study is conducted by searching the worldwide websites, journals and articles to know AMD pathogenesis, what kind of substances take place in the progression of the disease, reviewing the potential substances in inhibiting the pathogenesis process, and reviewing substances in tempeh which has effects on certain process in AMD neovascularisation. AMD progressively destroys the macula (the central portion of the retina) and thereby impairs central vision. In the retina, angiogenesis is an important component of normal physiological events and is also involved in pathological processes. It has been suggested that hypoxia could be the primary stimulus for ocular neovascularization and hypoxia-induced angiogenic factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). Antiangiogenic drugs are stopping neovascularization in wet macular degeneration. Recent reports indicated that genistein, a naturally occurring isoflavonoid exhibits strong antiangiogenic activity. The genistein significantly inhibited hypoxia-elicited bFGF protein expression in a concentration-dependent manner. Genistein suppresses the activation of bFGF receptor and adversely manipulate the expression of bFGF protein in RPE cells through autocrine way; proving the hypothesis that genistein have an important application in the treatment of retinal and subretinal neovascularization. Keywords: Age-Related Macular Degeneration (AMD), neovascularization, genistein, tempeh
WEIGHT BEARING EXERCISES TO REDUCE THE RISK OF FRACTURE IN ELDERLY PATIENT WITH OSTEOPOROSIS El-nissi, Jefryanto, Kezia Joselyn, Stefina Gunawan University of Kristen Krida Wacana
Synopsis: Osteoporosis is one of the big public health problems, especially for elderly. It has been identified as one of 10 most important conditions affecting the entire human race. World Health Organization (WHO) defined osteoporosis as a skeletal disease, characterized by low bone mass and micro-architectural deterioration of bone tissue, with consequent increase in bone fragility and susceptibility to fracture. Osteoporosis leads to risk of falls and fractures. In elderly, these fractures can have numerous effects of function and quality of life. It is important to prevent multiple fractures that can lead to mortality. Specific weight-bearing exercises in three key fracture sites (wrist, hip, and spine) have shown tremendous improvement of boneâ&#x20AC;&#x2122;s resistance and consequently reduce the risk of fracture. Weight-bearing exercises include jogging, walking, stair climbing, dancing, and soccer. In these exercises, bones and muscles are pushed to work against gravity. Since gravity is holding them down, endurance is required to move against it. Bone is mechanosensitive, therefore a sufficient magnitude of the external forces loaded upon the bone is needed to create a fluid flow within the lacunarâ&#x20AC;&#x201C;canalicular network to stimulate bone formation. Mechanical loading stress on bone causes tissue deformation within bone that stimulates the bone to adapt by remodeling to oblige these demands, and ultimately improve boneâ&#x20AC;&#x2122;s resistance to fracture. It takes around 3-4 months for the completion of the bone remodeling cycle (bone resorption, formation, mineralization). Therefore, training should be held for at least 6-8 months to fully obtained the potential changes in structural properties. Keywords: osteoporosis, elderly, fractures, weight-bearing exercise
BACKPACK FOR WOMAN TREND AS POSTURE-TRAINING SUPPORT FOR OSTEOPOROSIS PREVENTION Fabianto Santoso, Cynthia Viryawan, Andy William, Shelly University of Indonesia
Synopsis: Osteoporosis is a common disease of the elderly. International Osteoporosis Foundation (IOF) chapter Indonesia reported that prevalence of osteoporosis in Indonesia is about 28,8% men and 32,3% women. On other hand, prevalence of osteopenia is more bigger; 41,8% in men and 90% in women. Postural kyphosis is one of the consequence of osteopenia. Prevention aims to maximize bone density and improving posture for minimize fracture risk so it could improve quality of life. In this poster, the authors explain about posture-training support for osteoporosis prevention, especially vertebrae, to prevent kyphosis. Using literature review to gain data to be analyzed and synthesized, it is then known the concept of backpack for woman is adapted from orthoses which is used to treatment osteoporosis. One study explained about design orthoses for posture-training support is like mini backpack that contains 680 gram or about 1,5 pound. We need role of many parties to implementation this trend. The study concludes that the trend of backpack for women can be one of prevention methods for osteoporosis in women so that minimize postural kyphosis and its burden in oneâ&#x20AC;&#x2122;s quality of life and so on.
POTENTIAL OF GLUCAGON-LIKE PEPTIDE 1 (GLP-1) ANALOGUES IN THE TREATMENT OF ALZHEIMER’S DEMENTIA THROUGH POTENTIATION IN INSULIN SIGNALING Andy William, Shelly, Fabianto Santoso, Cynthia Viryawan University of Indonesia
Synopsis: Alzheimerâ&#x20AC;&#x2122;s disease (AD) dementia is a debilitating disease characterized by cognitive impairment which commonly affects people over 65. The prevalence of AD worldwide in 2010 is 35.6 million people and is estimated to be doubled in 2030. As of today, available treatments are only symptomatic. AD is characterized by accumulation of A! plaques, which are thought to trigger the disease. Therefore, treatments investigated in the past focused in targeting these plaques. However, the clinical trials investigating the efficacy of antibody against A! plaques has been producing disappointing results. Therefore, there needs to be a shift in perspectives of the pathogenesis of AD. This review aims to assess the efficacy of intranasal GLP-1 analogues in the treatment of AD dementia. Defective insulin signaling in brain is an early event that precedes AD dementia. Normally, insulin would bind to insulin receptor (IR) and activates IRS-1, which in turn activates PI3K pathway. This pathway is important in maintaining neural haemostasis. In AD, A! oligomers which results from chronic stress cause insulin resistance, which induce neuronal apoptosis. GLP-1 is an incretin which act as insulin sensitizer. By binding to GLP-1 receptor, it can also activate PI3K pathway. GLP-1 analogues (liraglutide, exentide) has the advantage over its endogenous form by being resistant to DPP-4, thereby prolonging its half life. Preclinical studies involving alzheimer mouse models indicate that GLP-1 analogues can improve neurogenesis and clearance of A! plaques. If applied intranasally, it can reduce its side effects and improve its penetration through blood-brain barrier. And so it is concluded that intranasal GLP-1 analogues has the potential to be the treatment of AD Dementia. However further clinical trials need to be done to confirm its efficacy.
ANTIOXIDANT EFFECT OF CLITORIA TERNATEA TO PREVENT LENS OPACIFICATION IN AGE-RELATED CATARACT Felix Lee, Jevi Septyani, Shirley Ratnasari University of Indonesia
Synopsis: Cataract is a disease with high prevalence among elderly people. If left untreated, it could cause blindness and hence decreasing quality of life in patients. Indonesia was reported of having the highest cataract cases among all Asian countries in 2012. The only available treatment for cataract is through surgery. However, cataract removal demands a high cost procedure and usually patient may need additional medications and specific eye care after the surgery. Clitoria ternatea plant extract has a potential to prevent the worsening symptoms of cataract by its antioxidant property. Besides, Clitoria ternatea is found abundant and cheap in Southeast Asian countries, like Indonesia. The objective of this scientific poster is to give information about the potential and benefits of Clitoria ternatea as the new possible alternative treatment in the future for age-related cataract aside from surgical treatment. Literature review from trusted medical textbooks, journals and websites. All of the information obtained from the resources are then analyzed systematically and sought the correlation through logical reasoning to deduce a conclusion. A study showed that Clitoria ternatea contains polyphenol compounds, like 1,2,3,5Cyclohexanetetrol and flavonoid, which give its antioxidant property by suppressing Fentonâ&#x20AC;&#x2122;s reaction, and hence Reactive Oxygen Species, which could oxidised the lens protein, are not produced. Another experimental study showed that after administering Clitoria ternatea extract to rats, there are increase level of reduced glutathione (GSH) and increase activity of antioxidant enzymes, like superoxide dismutase, catalase and glutathione peroxidase. Clitoria ternatea plant extract has a potential to prevent severity of age-related cataract through its antioxidant activity. Besides, it is readily available and low-cost in Indonesia. However, further research is needed to prove the efficacy of this plant extracts to treat agerelated cataract. Keywords: Age-related cataract, Clitoria ternatea, antioxidant, polyphenol compounds
THE USE OF VARIOUS TRAINING PROGRAMS TO IMPROVE BALANCE AND REDUCE FALLS IN ELDERLY PEOPLE: A LITERATURE REVIEW A.A. Putu Sandra, Abdullah Rayhan, Betty Merdiani Putri University of Trisakti
Synopsis: This literature review was aimed to determine the use of various training programs and the impact to physical abilities as part of fall prevention in elderly people. Besides the ultimate aim, guide in selecting an appropriate exercise according to the condition of the elderly. The research journals were conducted using Medline, PubMed, Researchgate, Oxford Journal, Indian Journal, Elsevier, Wiley Online Library, and etc. The search included article in English language, human, elderly, people aged 65+ years, and time span 2000 until 2014. The search field being the title and abstract. The key words used are falls, falling, prevent, prevention, reduce, training, exercise, water, land, elderly, older. From the research, it is known that prevention held in many hospital and alternative institutions give a significant improvements in improving the balance, neuromuscular performance of not only those of elder patients with abnormal posture, neuromuscular disorder, or bone disease, but also in the normal life to prevent fall and improving health and quality of life. After fall prevention program continue to be accepted around the world, the studies prove that it give significant improvement in elder patient. The main task now is to increase the awareness of society. Key words: Fall Prevention, Land and Aquatic fall prevention exercise, WBVT
INNOVATION FOR OSTEOPOROSIS VACCINATION: THE ROLE OF ANTI-SCLEROSTIN ANTIBODY AS SCLEROSTIN INHIBITOR IN OSTEOPOROSIS PREVENTION ON HIGH RISK GERIATRIC PEOPLE Thoha Muhajir A., Kharisma Ridho H., Rahadi Akbar., Nur Afiati Nadhiyah., Januardi Indra Jaya University of Brawijaya
Synopsis: Osteoporosis is a silent disease characterized by low bone mass which are associated with reduced bone strength and increase of fracture risk. Osteoporosis is the second worldwide disease problem after heart disease. Osteoporosis occurs because the unbalanced activity of osteoclast as a bone resorption cells and osteoblast as a bone formation cells tha. Osteoporosis occurs both men and women, but mostly on postmenopausal women older than 50 years old. Initial therapy for osteoporosis treatment due to menopause is anti-resorptive agent that can not stimulate bone formation, also paratyroid hormone (PTH) that can stimulate bone formation, but also has ability to stimulate bone resorption so become less effective. Recent study show that antibody anti-sclerostin can stimulate bone formation without stimulating bone resorption. So
one of the solution is to induce antibody anti-sclerostin as the prevention of osteoporosis in high risk geriatric people. Sclerostin is a protein produced by SOST gene expressed by osteocytes in the human bone. Sclerostin act as a negative regulator in the bone formation. Individu with sclerostin deficiency has high bone mass, increased bone strength, and resistance to fracture. Sclerostin works by inhibiting the Wnt and bone morpho-genetic protein signaling pathways that are critical for osteoblast proliferation and activity. Monoclonal antibodies were obtained and characterized using bacterially expressed and insect cellâ&#x20AC;&#x201C;expressed recombinant scl. Inhibition of sclerostin by systemic adminitration of Antisclerostin monoclonal antibody increased bone formation, bone mass, and bone strength in nonfractured bones in non human primate models.!So this antibody-mediated blockade of sclerostin represents a promising new prevention approach for the anabolic prevention of people with high risk bone-related disorders, such as postmenopausal osteoporosis. Keywords: Osteoporosis, Sclerostin, Wnt Signalling, Monoclonal Antibody
GERIATRIC DIABETIC CLINICAL MANAGEMENT: A CONCEPT OF CARE TO THE ELDERLY SUFFERING FROM DIABETES MELLITUS TYPE-2 Asa Mutia Sari University of Diponegoro
Synopsis: Diabetes Mellitus (DM) is one of the most common chronic diseases affecting older persons, and the prevalence of DM has increased exponentially throughout the world. As it is in the model geriatric care & clinical management of DM type 2, the benefit to risk ratio is to be assessed when treating this particular patient population. This particular is aimed at making the reader more understand the roles of geriatric care & clinical management and how it affects the people with diabetes type 2 in the elderly. Understanding the special dynamics of geriatric patients by geriatric care & clinical management will aid in the optimum management of their diabetes. Randomized clinical trials and systematic reviews of International journals and some research was searched for relevant data and guidelines on each DM type 2 topic. Evidence tables were constructed summarizing new evidence. Management of DM is highly challenging
in the elderly. The main goals during
management include : â&#x20AC;˘ Optimizing functional and daily routine activities. â&#x20AC;˘ Avoidance, minimizing and preventing microvascular and macrovascular complications. The management of older adults with type 2 diabetes requires careful consideration of the effects that advancing age and changes in health status can have on the competing risks and benefits of therapeutic interventions. Ideal geriatric care requires a multidisciplinary approachand interaction with geriatricians, diabetologists, pharmacists, social workers, diabetes educators, and dietitians to ensure the most efficacious treatment.
? Public Poster
YOU CAN’T AFFORD TO WAIT WHEN IT COMES TO STROKE Hasbi Abdul Rozak, Farah Shafira University of Jenderal Achmad Yani
Stroke is a serious, life-threatening medical condition that occurs when the blood supply to part of the brain is cut off. Older people are most at risk of having strokes. If you are south Asian, African or Caribbean, your risk of stroke is higher. Most of you know that stroke is a common disease especially in elder people but most of you also donâ&#x20AC;&#x2122;t know what to do and whatâ&#x20AC;&#x2122;s going to happen next and it will increase the chance of the complications to occur such as brain swell, high blood sugar, high blood pressure, blood vessel spasm, coma and even death. Firstly, to prevent those complication you have to recognize the general symptom of stroke such as sudden weakness or numbness in the face, arm, or leg on one side of the body. Abrupt loss of vision, strength, coordination, sensation, speech, or the ability to understand speech. Sudden dimness of vision, especially in one eye and there are so many left but these are easily recognized. Strokes are a medical emergency and urgent treatment is essential because the sooner a person receives treatment for a stroke, the less damage is likely to happen. Treatment depends on the type of stroke you have, including which part of the brain was affected and what caused it and your doctor know it the best. Most often, strokes are treated with medication. This generally includes medicines to prevent and remove blood clots, reduce blood pressure and reduce cholesterol levels. In some cases, surgery may be required to treat brain swelling and reduce the risk of others complication. You will also recommended to join a community that will help you heal. So, when you feel S.A.F.E run to your doctor with no doubt!
!
DEPRESSION IN THE ELDERLY Qonita Farah Faadhilah University of Sriwijaya
Depression in the elderly is a common psychosociogeriatric problems, not a normal part of aging. Depression in the elderly needs to be taken seriously. Many factors contributed to depression in the elderly, among which are health problem, loneliness, fears, recent bereavement and reduced sense of purpose. Recognizing depression in the elderly starts with knowing the signs and symptoms, there are sadness, fatigue, weight loss, losing interest in hobbies, social withdrawal, sleep disturbance, increased use of drugs and negative thoughts. There many ways to prevent and help a depressed senior, and social support is amongst the most important factor for helping the elderly. This poster aims to provide information about depression in the elderly, so that the public especially the young generation can recognize and care towards depression in the elderly.
! ! ! ! ! ! ! !
ABC OF HEART ATTACK Euginia Christa, Teresa Wulandari, Nadhira Anindita Ralena University of Indonesia
!
Myocardial infarction (MI), most commonly referred to as heart attack, is a heart disease which is caused by the blockage of coronary arteries that delivers oxygen and nutrients to heart cells, resulting in necrosis of myocardial tissues. MI is one of the most prevalent coronary heart diseases (CHD) that are found in Indonesia. Predisposing factors includes sex, increasing age, unhealthy living habits and concomitant illnesses such as hypertension and obesity. According to WHOâ&#x20AC;&#x2DC;s data published in 2011, 17.05% of the total death in Indonesia is caused by CVD, responsible for one of the largest cause of deaths. Patients with MI accounts for 74.8% of all patients with CVD. The prevalence of death among MI patients increases with age, from 11% in the 35-44 years group to 33.2% in 55 years or older group. This indicates that the incidence and prevalence of MI increases with age. Symptoms of heart attack are most of the time obvious although it may be silent as well. Geriatrics that are affected may not realize that something is wrong, hence causes the delay in treatment. The prompt response towards MI may safe a live. If the heart is revived within one hour of attack, the survival rate is improved by up to 50%. However, the chance of surviving is reduced to only 23% if treatment is given within 3 hours after attack. Every 15 minutes of delayed treatment increases the probability of death by 1.6 times. According to this understanding, we decided to create this poster with the aim to improve peopleâ&#x20AC;&#x2DC;s awareness on how to recognize the signs of heart attack so that punctual realization and response towards MI can be done and more lives can be saved.
! ! ! ! ! !
THE WORLD THROUGH YOUR GRANDPARENTâ&#x20AC;&#x2122;S EYES Hansens Yansah, Nathania Sutandi University of Indonesia
! ! ! ! ! ! ! ! !
A leading cause of blindness in diabetics worldwide, Diabetic Retinopathy, is a disease that induces change in the blood vessels of the retina. The retina requires a constant supply of blood from small blood vessels to work effectively, in diabetic individuals however, a high-glucose concentrated blood constantly flows into the small network of vessels, this results in narrow, bleeding, or leaking blood vessels. Individuals with diabetic retinopathy experience one of two conditions; swelling blood vessels which will leak, or abnormal growth of new blood vessels on the surface of the retina. Indonesia has over nine million individuals with diabetes, a feat that has placed Indonesia on rank four when compared to other nations worldwide (WHO). According to a study created by DiabCare Asia in 2008, 42% of patients with diabetes in Indonesia also suffer from diabetic retinopathy additionally the risk for diabetes increases as you age. Unfortunately, late diagnosis of DM in low socioeconomic level patients may ultimately lead to progressive diabetic retinopathy (blindness). This poster has been created in the hopes of spreading the word to youths that their grandparents, too, could harbour this condition and without the proper diagnosis blindness may ensue. There are various ways of improving the condition of patients with diabetic retinopathy, but we chose to focus on active lifestyle and regular monitoring as is it the easiest to apply to Indonesia. Diabetic retinopathy is not a disease that will instantaneously cause blindness, but rather, it is a progressive disease. Upon the onset of such signs and symptoms, screening methods called comprehensive dilated eye screening can monitor the progression of the disease. The disease itself is not an inherited disease but the presence of diabetes in your genetic compound will leave a scar for generations to come.
! ! ! !
WE CARE! Fadhian Akbar, Adrian Reynaldo University of Indonesia
! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
The increasing of aged people Indonesia will be resulted in the the increasing the risk of the chronic disease among the geriatric. Based on the research, the risk of chronic disease increase 65% among the geriatric. If we canâ&#x20AC;&#x2122;t promote the health of geriatric, it is not impossible in the future when the geriatric is the phase of people to become sick. Unfortunately, It will be the burden of our health sector if we can face this risk. Geriatric have right and have needs same as us, but they are limited by their inability. As the young people, we can care to them. Start from serve them as the special age-group, for example provide them with proper facility. Then, we can also support them in fulfill their need. So, they can save from the threat of so many disease. From this poster, we hope we can raise the people awareness in supporting geriatricâ&#x20AC;&#x2122;s life. Hopefully, people around us will have an awareness to help and support the geriatric. ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
SLOW THE PROGRESS, KEEP THE MEMORIES Aristya Nur F, Meutia Julyta, Rabitah Adila, Rizka Nurhayati University of Trisakti!
As the life expentancy increased, the number of elderly worldwide has also increased. As of 2010 the number of people 65 and older is 531 million and it is projected to be 1.5 billion in 2050. As the number of the elderly increased, it’s expected that the “grey” diseases—chronic non-communicable diseases such as heart and lung problems, stroke and kidney failure—to increase. While the most common causes of disability in elderly are dementia, visual impairment, hearing loss, and osteoarthritis. Most people think that when elderly misplaced things and kept forgetting things are common occurances in their old age, while to some degree it is normal we must bear in mind that memory impairment especially when accompany with personality changes are in fact the only early signs of dementia. Dementia is a syndrome that usually is progressive in nature, caused by neurodegenerative disease—causing the brain cell to die—thus affect the memory, thinking, behavior, and ability to perform everyday activities. The total number of people with dementia worldwide in 2010 is estimated at 35.6 million. This proportion is projected to rise to 71% by 2050. As of now, there’s no known cure to stop the progress of dementia and because of this we want to raise the awareness of dementia on how to slow the progress of it since that is the only thing we can do right now. And how actually we can do that? It’s by doing things that can stimulate our brain such brain games (such as puzzle and chess), keep your daily activities in regular schedule as you come to your old age as to not makes you forget easily, and don’t forget to keep a healthy diet.
FIGHTING TO REMEMBER Pratiwi Siswaji, Prazna Shafira, Savina Umar University of Trisakti
Alzheimer's is a disease of the brain that causes problems with memory, thinking and behavior of human. It's the most common cause of dementia — a group of brain disorders that results in the loss of intellectual and social skills — that is neither normal aging nor mental illness of human being. In Alzheimer's disease, the brain cells themselves degenerate and die, causing a steady decline in memory and mental function. Increasing age is the greatest known risk factor for Alzheimer's. With Alzheimer’s, it is not just those with the disease who are impacted but also their caregivers. Caring for a person with Alzheimer’s is often very difficult and, in fact, many family or friend caregivers experience high levels of emotional stress and depression as a result. Alzheimer's gets worse over time and ultimately is fatal. Although symptoms can vary widely, the first problem many people notice is forgetfulness severe enough to affect their ability to function at home or at work or to enjoy lifelong hobbies. Other symptoms include confusion, getting lost in familiar places, misplacing things, and problems with speaking and writing. A person with Alzheimer's disease may not be able to communicate that he or she is experiencing pain, report symptoms of another illness, follow a prescribed treatment plan and notice or describe medication side effects. As Alzheimer's disease progresses to its last stages, brain changes begin to affect physical functions, such as swallowing, balance, and bowel and bladder control. New programs targeted to people at high risk of dementia are being developed. These multicomponent programs encourage physical activity, cognitive stimulation, social engagement and a healthy diet. They also teach memory compensation strategies that help optimize daily function even if brain changes progress.
Share, Help, and Care for Alzheimer Fadhilah Aliyah Nur Imani Saptogino, Reika Ravenski Novsa, Renata Eka Nindya Anggadewi, Rizkya Amelia University of Trisakti !
Alzheimer disease (AD) is the most common form of dementia. There are no available treatments that stop or reverse the progression of the disease, which worsens as it progresses, and eventually leads to death. There are currently no specific markers that can confirm with a 100% certainty AD diagnosis and the mechanisms still does not exist. According to World Health Organization, Alzheimer disease (AD) has become a major public health concern as the world’s population ages. It is projected that by 2050, people aged 60 and over will account for 22% of the world’s population with four-fifths living in Asia, Latin America or Africa. In Indonesia about 5-6% at ages over 60th eam diagnose with Alzheimer and it is the seventh leading cause of death in the United States. In the early stages, people living with Alzheimer become forgetful, especially regarding things that just happened, show orientation difficulties, and have difficulties in making decisions, and in carrying out household tasks. In the middle stage, all of these symptoms become worse, become very forgetful, difficulties in communication increase and need help with personal care. In the final stages memory disturbances are very serious and the physical side of the disease becomes more obvious. Anne Frank quotes said “No one has ever become poor by giving.” From this poster, we hope people, especially people closest to them want to share their love, help them anytime, anywhere, and taking care of the person with Alzheimer because they really need it. It also depends on family, society, and governments contributions to improve the quality of people with AD life.
!
THE LIFE YOU SAVE DOWN, THE LINE MAY BE YOUR OWN Andhika Rezky Bahrizal, Atika Rosada, Ayang Rashelda Maulidinia, Carmelita Christina, Maria Mega A, Nadya Carolina, Tiara Larasati J P University of Trisakti
! !
!
Nowadays, numbers of elderly who get abused is increasing. However, most of people do not concern much about it, especially verbal abuse. People do not know that those verbal tortures can give bad effects on elderly such as depression, social isolation, insomnia, and anxiety disorders. Another possibility is that some people may be simply carefree about it. They will think their words will soon be forgotten. In fact, most elderly tend to be more sensitive to the words they heard. Those words may echo in their minds, then they will feel useless and hard to sleep. Those are reasons why we choose verbal abuse as an essential point to be aware of. The phrases we use as a tagline, "The Live You Save Down, The Line May Be Your Own" is purposed to wake people up, and let them think again about what they have said, accidentally or intentionally. It means the elderly may be in danger because of the bad words we said to them. As it has stated before, those elderly may have psychological disorder ranged from mild to severe ones. After reading the tagline we wrote big and clear, we hope people will be more careful on words they are going to say. The girl whose expression is angry while shouting at an old man, supported with little words as the background, shows a great illustration about verbal abuse. A good combination of dark purple and dark grey represent a dark days that come to elderly who got verbal tortures. We provide website on this poster so that people know how to find more information and what to do next when they found any verbal abuse on elderly. Words can break someone into pieces, so use ours for good. That is all we made this poster for. !
OPEN YOUR EYES TO THE ISSUES AND PROTECT THE ELDERS Azlina Darsaniya Wandawa, Fadia Mutiaratu, Audriana Hutami Putri, Fadhilannisa Rinanda, King Panji Islami, Heike E.H University of Trisakti
! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
In general, elder abuse is a term referring to any knowing, intentional, or negligent act by a caregiver or any other person that causes harm or a serious risk of harm to a vulnerable adult. Each year hundreds of older persons are abused, neglected, and exploited. But it is typically underreported globally. Prevalence rates in selected developed countries (such as Indonesia) - ranging from 1% to 10%. Many victims are people who are older, frail, cannot help themselves and depend on others to meet their most basic needs. In Indonesia, there are some laws that regulate these issues, one of them is UU No. 13 TAHUN 1998 about safety or welfare of the elderly. Laws and definitions of terms vary considerably from one state to another, but broadly defined, abuse may be: physical abuse, sexual abuse, neglect, exploitation, emotional abuse, abandonment, and self-neglect. At first, you might not recognize or take seriously signs of elder abuse. They may appear to be symptoms of dementia or signs of the elderly person’s frailty. In fact, many of the signs and symptoms of elder abuse do overlap with symptoms of mental deterioration, but that doesn’t mean you should dismiss them. While one sign does not necessarily indicate abuse, some signs that there could be a problem are: bruises, frequent arguments, change in personality or behavior, and many more. But most importantly, be alert. The suffering is often in silence. If you notice changes in an elder’s personality or behavior, you should start to question what’s going on. What should we do next? Report this case to the authorities. Report this to KOMNAS LANSIA. KomnasLansia is governmental organization that coordinates the communication between government and society in performing services for the elderly. So, open our eyes to the issues and protect our elders.
IS IS A STROKE ? RECOGNIZE THE SIGN F.A.S.T ! Azlina Darsaniya Wandawa, Fadia Mutiaratu, Audriana Hutami Putri, Fadhilannisa Rinanda, King Panji Islami, Heike E.H University of Trisakti
A stroke is not a heart attack. A stroke happens when the supply of blood to the brain is suddenly interrupted. Brain cells die when they no longer receive oxygen and nutrients from the blood (ischemic stroke) or there is sudden bleeding into or around the brain (hemorrhagic stroke). Some strokes are fatal while others cause permanent or temporary disability. According to the World Health Organization, 15 million people suffer stroke worldwide each year. Of these, 5 million die and another 5 million are permanently disabled. In Indonesia, the mean age of stroke patients is 58.8 years. Knowing the signs and symptoms of a stroke is the first step to ensuring medical help is received immediately. For each minute a stroke goes untreated and blood flow to the brain continues to be blocked, a person loses about 1.9 million neurons. Face dropping on one side, arm weakness & numbness, and also difficulty with speech are the most common symptoms or signs of stroke. But they are not the only signs. Other signs of stroke may include one, or a combination of dizziness, loss of balance or an unexplained fall, loss of vision, headache, and difficulty swallowing. The signs of stroke can last a few seconds or up to 24 hours and then disappear. When symptoms disappear within 24 hours, this episode may be a mini stroke or Transient Ischaemic Attack (TIA). The longer a stroke remains untreated, the greater the chance of stroke related brain damage. Emergency medical treatment soon after symptoms begin improves the chance of survival and successful rehabilitation. Act F.A.S.T (Face dropping on one side, Arms weakness & numbness, Speech difficulties, Time call 119 for emergency) is an easy way to remember and identify the most common symptoms of a stroke. Recognize the signs and calling 119 will determine how quickly someone will receive help and treatment. Getting to a hospital rapidly will more likely lead to a better recovery. The faster you act, the more of the person you save.
PREVENTING ALZHEIMERâ&#x20AC;&#x2122;S DISEASE; WHAT DO WE KNOW ? Hardi Hutabarat, Mariska Regina - Indonesia Christian University
Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills and, eventually even the ability to carry out the simplest tasks of daily living. In most people with Alzheimer’s, symptoms first appear after age 65. Alzheimer’s disease is the most common cause of dementia among older people. Alzheimer's disease is the 6th leading cause of death in the United States. More than 5 million Americans are living with the disease and every 67 seconds someone in the United States develops Alzheimer's. 1 in 3 seniors dies with Alzheimer's or another dementia. But in indonesia, we still dont have a valid data about prevalensi of Alzheimer. Alzheimer’s is a slow disease that progresses in three stages an early, preclinical stage with no symptoms, a middle stage of mild cognitive impairment, and a final stage of Alzheimer’s dementia. The time from diagnosis to death varies as little as 3 or 4 years if the person is older than 80 when diagnosed to as long as 10 or more years if the person is younger. Currently, Alzheimer’s disease has no known cure, but recent research results are raising hopes that someday it might be possible to delay, slow down, or even prevent this devastating disease. So, early diagnosis and prevention is the best way to decreased prevalensi of Alzheimer’s disease. Alzheimer’s disease have a several sign such as memory loss, trouble with familiar tasks, difficulty solving problems, misplacing item, difficulty with word, etc. Knowledge about the signs of Alzheimer is very important for society.After we know the signs of Alzheimer’s disease, we know hot to prevent Alzheimer such as regular excercise, eat a healty diet, mental stimulation, etc. We hope by increase knowledge of alzheimer and do a early diagnosed are the best way to decreased prevalensi Alzheimer’disease. !
DEMENTIA : SEEK BEHIND THE FACE Ryka Marina Walanda – University of Tadulako
Dementia is disenabling for the sufferers and their families, and brings impact throughout the society especially for aged care and carer services. Dementia isn’t a single disease but refers to the manifestation of progressive irreversible neurological degeneration. It is characterized by impaired cognitive function, with memory loss, confusion, and personality change, and also often accompanied by co-morbidities. While there are many types of dementia with different causes, the main risk factor is ageing. Prompt diagnosis of dementia facilitates access to education and support, pharmacotherapy, cognitive training and communication therapy, all of which can significantly contribute to better outcomes, slowed disease progression, and a reduced carer burden. Sadly, diagnosis of dementia depends of recognizing gradual changes, is hindered by misconception by society and thus there is little role for healthcare intervention and also may be reasons of fear, denial and dismissal of signs as “normal ageing”. This poster aims to notify the prevalence of dementia, difficulties in its diagnosis and management, and encourage society’s awareness to reduce stigma and the discrimination of dementia.
! !
DONâ&#x20AC;&#x2122;T LOSE YOUR HOPE IN YOUR AGED LIFE! Monica Djaja Saputera, Vanessa Priscillia University of Tarumanagara
Indonesia is a part of the South-East Asian Nations, which means that Indonesia still have some oriental cultures. As we know that Indonesian people have the similarity with the Chinese and Japanese people who like to drink tea every day. But do you know that tea, especially green tea have a positive effect for elderly people? According to World Health Organization, the number of elderly people will increase to 2 billion in 2050. The increasing number of elderly people means that there will be many challenges for each country to handle those problems. Cognitive dysfunction is one of the challenges that needs care from every aspects, but the most important is to prevent the disease or prevent the progress of cognitive dysfunction. Based on some researches, green tea is known for having many effects in human body. Kazuki Ide (2014) shows the result that the consumption of green tea every day during meals is effective in improving cognitive function or reducing the progress of cognitive dysfunction on elderly people. The goal of this poster is to inform all of the people including medical students and general physicians about the benefit of drinking green tea in cognitive function. So, we hope that this poster will help the elderly people reduce the risk of cognitive dysfunction and give them happy life on their old age. Decreasing the risk of cognitive dysfunction means decreasing the challenges for the country too.
! ! ! ! ! ! ! !
MAKE EVRY(B)ONE MOVE Made Ayu Mutiara Dewi, Eka Pratiwi, Nabila Resti, Elan Aisyafuri
OA as one of the common disease have decreased quality of life of millions elderly. In Indonesia, there are 36,5 millions cases of OA in 2007, and the number increases every year. It affects the protective cartilages on the ends of the bone and makes them break down over time. This causes the bones to rub against each other, causing stiffness, pain and loss of joint movement. Osteoarthritis often gradually worsens, and no cure exists. But it can be prevented by maintaining weight control and staying active. Avoid any injuries, maintain healthy life style, and see your doctor regularly may also slow progression of the disease and help improve pain and joint function. By doing all of the stuffs that we are propose, we want to make every bone to stay healthy and we want everyone to be able to move as long as they can.
DEMENTIA IS NOT A NORMAL PART OF AGING Jonathan Alvin N.H. & Amanda Kristiani University of Diponegoro
Nowadays, it is estimated that 35.6 million people worldwide have dementia, where most of them (58%) living in developing countries. The proportion of population aged 60 and over with dementia at present time is between 2 to 8 per 100 people. However it is projected that this number will almost be doubled every 20 years, to 65.7 million in 2030 and 115.4 million in 2050. Dementia is a syndrome in which the cognitive function declining beyond normal ageing. The symptoms include memory loss, difficulties with planning, problem-solving or language and sometimes changes in mood or behavior. It affects memory, thinking, orientation, comprehension, calculation, learning capacity, language, and judgment. Dementia is progressive and it is caused by physical changes in brain. There are many known causes of dementia â&#x20AC;&#x201C; probably more than 100. The most common types are Alzheimerâ&#x20AC;&#x2122;s disease and vascular dementia. Some people have a combination of these, known as mixed dementia. Dementia is one of the major causes of disability and dependency among older people worldwide, There is often a lack of awareness and misunderstanding of dementia, resulting in stigmatization and barriers to diagnosis and care.
! ! ! ! !
ADHERENCE IN ELDERLY HYPERTENSION, YOUTH RESPONSIBILITY Christian Tricaesario - Sarah Fauzianisa - Claudia Mary J - Priscilla Jessica - Gita Ayu Rachma University of Diponegoro
Hypertension is chronic condition where the arterial blood pressure is elevated that can be caused by many diseases or circumstances. Hypertension is commonly found in elderly as their bodies undergo ageing. In most people with primary or essential hypertension, increased total peripheral resistance to blood flow â&#x20AC;&#x201C; due to narrowed small arteries and arterioles or decreased elasticity of the blood vessels â&#x20AC;&#x201C; accounts for the high blood pressure condition. Hypertension increases the risk of ischemic heart disease strokes, peripheral vascular disease, and
other
cardiovascular
diseases,
including heart
failure, aortic
aneurysms,
diffuse atherosclerosis, and pulmonary embolism. Hypertension is also a risk factor for dementia and chronic
kidney
disease. Other
complications
include hypertensive
retinopathy and hypertensive nephropathy. So it is an important condition for people to be aware of, especially for elderly. One of several ways in managing Hypertension is by using medications. There are some classes of drugs, collectively called antihypertensive drugs, to treat this condition. Once someone has taken antihypertensive drugs, they have to take it for lifetime. If they cut their medications because feeling better or feeling not sick, it may worsen their hypertension and cause other complications. A study of 73,527 patients with hypertension, published in the European Heart Journal, found that patients who did not adhere to their medication had a four-fold increased risk of dying from stroke in the second year after first being prescribed drugs, and a three-fold increased risk in the tenth year, compared with adherent patients. So compliance in taking antihypertensive drugs is highly needed, and for elderly of course it is not easy as they maybe forget to take one or they donâ&#x20AC;&#x2122;t understand the function of these drugs. Thus, it is our duty to give them comprehension and to remind them in taking their medicines.
LOST IN TIME Mona Galatia, Alicia Sandjaja, Kristiani! University of Diponegoro Are you scared being old? Old age is a condition which mankind has always reluctantly
recognized and always with resignation that relates with memory loss. Although it is realize that Alzheimerâ&#x20AC;&#x2122;s disease destroys the brain memory function, many do not realize precisely how the memory is destroyed once one is aware of the process, it becomes faster to work forward to alleviate the destruction. Alzheimerâ&#x20AC;&#x2122;s disease is a neurological disorder in which the death of brain cells causes memory loss and cognitive decline. It often happens in people about over 65 years old, but there is possibility happens too with people below 65 years old. Based on the report of Alzheimerâ&#x20AC;&#x2122;s Association, there are 44,35% people who suffered from Alzheimer and every year the probability can increase risk about 10 to 20%. What are the symptoms of Alzheimer Disease? Alzheimers Disease is a dementing illness which leads to loss of intellectual capacity. They usually hard to take in a remember new informations, such as forgetting events or appointments, getting lost on a familiar route, unable to solve simple arithmetic problems, hard to find the right word for a familiar thing. If one of the symptoms happens, we must directly go to the doctor. Doctor will give therapy and drugs as soon as possible to avoid big damage in our brain. Lifestyle choices can protect your brain. The six pillars of a brain-healthy lifestyle are Regular exercise, Healthy diet, Mental stimulation, Quality sleep, Stress management and An active social life. The more you strengthen each of the six pillars in your daily life, the healthier and harder your brain will be.When you lead a brain-healthy lifestyle, your brain will stay working stronger...longer. ! ! ! ! ! !
DARE TO CARE Andreas Yohan, Kevin Andersen, Jonathan Jose !"#$%&'#()*+,*-#.+"%/+&+*
* *
Nowadays, researchers have predicted that the number of people with Alzheimer's disease in the United States will have been doubled by 2050 and the cost of caring for Alzheimer's patients will be 5 times more expensive by then. Some researchers stated that the cost for treating Alzheimer’s patient will mostly be used for personal care. Hiring caregivers is a case in point. Even so,
We should have known that caregivers alone are not enough to cover the entire
population. Therefore, people should realize that they also need to care for them, especially the patient’s family members or colleagues. They can start by doing simple thing, such as giving a visit and care to them. Alzheimer is the most common form of dementia, characterized by memory loss and impaired intellectual abilities which have serious effect in daily life. Most people thought that dementia is a normal part of the aging, but it is not. Dementia ,caused by damage to brain cells, disrupts brain’s ability to communicate with each other. Alzheimer is a type of dementia with an accumulation of certain proteins, disturbing the communication of brain cells. 1 in 8 people older than 60 years old develop this type of dementia. There is no definitive cure for alzheimer at the moment. The purpose of this poster is to make people realize that alzheimer is common and could attack anyone, including their parents. So we invite them to respect and care for the elderly, especially those with alzheimer. In addition, we would like to give some useful tips to caregivers and family members how to reduce the risk of getting alzheimer and to improve their quality of life. We hope that this poster could help to drop the number of alzheimer’s patients and decrease the cost significantly in the near future
! ! ! !
LETâ&#x20AC;&#x2122;S FIGHT DEMENTIA WITH CARING! Tioky Sutjonong, Alvin Saputra University of Airlangga !
Over 20% of adults aged 60 and over, suffer from a mental or neurological disorder such as Dementia. Dementia is a syndrome that there is deterioration in cognitive function such as memory, thinking, and learning capacity. Dementia can be caused by injuries that affect brain such as Alzheimer’s disease. Dementia can be prevented! We don’t need to be a geriatrician, as youth we can prevent dementia too. Let’s fight dementia with CARING. C, Caring and make sure they have a quality sleep. By giving attention to their quality sleep, you have improved their brain function. Brain need to rest in order to function at optimum capacity. Deep sleep can be critical for memory formation and retention. A, An active social life. As a human we can’t live alone. Studies show that the more connected we are, the better we fare on tests of memory and cognition. We can make bond by spending time together like chatting with others. R, Regular intense physical exercise. Physical exercise can slow further deterioration in those who have already started to develop cognitive problem. The physical exercise must be aerobic and fun, such as walk at least 30 minutes or join an aerobic class but avoid a harmful movement. I, Improve brain activities. Just by reading news paper everyday, you can improve your brain activities. N, Nutrition has to be balanced. Brain needs food. A balanced diet can make brain operate at its best, so don’t forget to have a breakfast everyday. G, Guide and accompany them. By guide them and accompany them and make them happy, they will not stress, because stress has negative effect to the brain.
APPROACH YOUR ELDERS Jesslyn Valentina, Gerry, Liswindio Apendicaesar, Aura Razany University of Sebelas Maret !
Everyone wants happiness in their old age, but these expectations often do not become reality. Depression is the most often psychiatric problem occurs in elderly. World Health Organization (WHO) states that depression is on the order of four diseases in the world. This poster shows that many things are actually desired by elders. However, because of their limitations, their desires couldnâ&#x20AC;&#x2122;t be fulfilled. Depression can bring them many negative things, one of them is the lack of appetite which affects the lack of nutrients. In addition, their lack of mobility makes them unwilling to do physical activities. If they rarely socialize, they will feel lonely and meaningless, where is the spirit in that kind of life? In the end, depression can bring people closer to their death. Thereâ&#x20AC;&#x2122;s lot of things we can do as young people to be able to improve their living spirit. Firstly, pay attention to their diets every day. Monotone menus may decrease their appetite. Secondly, persuade them to have medical check-up. By knowing their own health condition, it will increase their confidence to live longer and also give positive effects to their mental condition. Furthermore, encourage and facilitate them to do some exercises. Those things can improve their both physically and psychologically life qualities. However, the most important thing, a little of your time for them, the moment you share with them can bring a lot of happiness. Approach your elders, they may need you to share with.
! ! ! ! ! ! ! ! ! !
!
ALZHEIMER, WHAT CAN WE DO ?! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
Alzheimer has attacked millions of people and become the 5th leading cause of death to people aged 65 and older. Moreover it may cause even more deaths than official source recognize. It kills more than prostate cancer and breast cancer combined and projected to kill triple more in 2050. Despite its position as a deadly disease, we know less of its pathogenesis and risk factor and we have not yet found a remedy to cure it or reverse its effect. So, what can we do? We can only detected it as soon as possible in order to get the maximum benefit from available treatment that may provide some relieve of symptoms and maintain a level of independence longer. It also beneficial because we will have more time to plan for the future because people with Alzheimer will have some difficulty to do their daily activity. In most case, the one who can recognize the early symptoms of Alzheimer is not the elderly itself, but the people around who interact with them. With this poster we want people to remembered the early sign of Alzheimer so they can help them to recognize it and treat it by bring them to doctor as soon as possible and making a good plan for their future so they will live in high quality of live even with Alzheimer. ! ! ! ! ! ! ! ! ! ! ! ! ! !
4 STEPS TO SAVE MEMORIES
Alzheimer's disease (AD), also known as Alzheimer disease, or just Alzheimer's, accounts for 60% to 70% of cases of dementia. It is a chronic neurodegenerative disease that usually starts slowly with the most common early symptom is difficulty in remembering recent events (short term memory loss). As the disease advances, symptoms can include: problems with language, disorientation (including easily getting lost), not managing self care, and behavioural issues. In 2010, there were between 21 and 35 million people worldwide with AD. It most often begins in people over 65 years of age, although 4% to 5% of cases are early-onset Alzheimer's which begin before this. It affects about 6% of people 65 years and older. In 2010, dementia resulted in about 486,000 deaths. It was first described by, and later named after, German psychiatrist and pathologist Alois Alzheimer in 1906. In developed countries, AD is one of the most financially costly diseases. It is truly one of a many diseases that needs attention. The role of the main caregiver is often taken by the spouse or a close relative. Alzheimer's disease is known for placing a great burden on caregivers which includes social, psychological, physical or economic aspects. Home care is usually preferred by people with AD and their families. Therefore, combining a few literatures we collected, we present the 4 steps to help preventing alzheimer. 1. Regularly exercise with proper diet 2. Mental stimulation to help brain-boosting 3. Be active in social life 4. Stress management
THE FIVE STEPS OF OSTEOPOROSIS
Osteoporosis is the condition in which a low bone mass and altered microarchitecture of the bone leads to increased risk of fracture. Traditionally, osteoporosis has been clas- si!ed into primary and secondary osteoporosis. Primary osteoporosis refers to osteoporotic conditions which are not related to other chronic illnesses and is usually associated with aging and decreased gonadal function, such as decreased level of estrogen, whereas secondary osteoporosis is the type of osteoporosis caused by other health problems. Disuse is one of the many reasons inducing bone loss and resulting in secondary osteoporosis.1 Indonesian health department stated that the prevalence of osteoporosis in Indonesia about 19.7% of the total population and the prevalence of osteopenia
47.1% (Indonesian
Nutrition research and development center in 2005). The increasing of life expectancy from 69.3 years (2007) becomes 71.1 years (2012) changed the composition of elderly and led to the higher risk of osteoporosis. Factors that may increase the risk of osteoporosis include: -
drop in estrogen after menopause
-
family history and body type
-
lifestyle factors and health conditions
-
lack of exercise
-
lack of calcium
Preventing Osteoporosis with ABCDE: a. a healthy lifestyle: quit smoking and keep alcohol consumption moderate b. bone care: discuss a bone density test with your healthcare practitioner if appropriate c. calcium: low-fat dairy products (200 to 300 milligrams per serving), drinking 2 glass of milk every day, canned salmon or sardines with bones, tofu and yoghurt d. vitamin D: 30 minutes of sun exposure a day and consume a healthy food. Vitamin D can be found in eggs, milk and oily fish. e. exercise: 45 minutes to one hour of aerobic activity two to three times per week ! !
THEY NEED NUTRITION MORE THAN WE DO! !
Society misconception about nutrition needed by elderly has been gone too far. Society think that elderly is enough to be given a random food as long as they will eat it without thinking the nutrition status of such a food despite it can make one to go to malnutrition and that condition can lead to an increase of chance of die because of infection, increase frequency of hospitalized, poor healing capability and decrease muscle strength which can increase the chance of falling accident. We are here want to tell society that they need nutrition as much as we are, event more than we are in order to maintain their metabolism and immune system working properly in this fragile situation. We want to promote the value to society or those who has elderly parents to care of nutrition problem to elderly around us by giving a healthful food, remember to make sure they got food regularly and care of the problem that can lower appetite like mouth and teeth problems. We hope the existence of this poster will raise the awareness of society, which to maintain the elderly to be healthy needs not only early detection and treatment but also a comprehensive solution to solve the problem of appetite and nutrition. ! ! ! ! ! ! ! ! ! ! !
HELP THEM FIGHT COPD!
COPD as one of the common disease in elderly killed thousands of people every years and projected to be the third biggest killer by 2020. Not only it kills thousand, itâ&#x20AC;&#x2122;s now considered to be one of the most troublesome diseases in elderly because it decreases millions of elderly quality of life. Now, people realize that shortness of breath is strongly related to quality of life because when they are breathless they can do less. Despite its position as a danger disease and its effect is irreversible, COPD is really easy to prevent. Passively and actively avoiding cigarette smoke that is the main risk for this disease, and remembering its symptoms and regularly doing a screening using spirometry will detected this disease earlier so the treatment can be prevented earlier and the disease progressivity can be limited as soon as possible. One problem remained when this deadly disease is not familiar in the society moreover to the elderly. So our task as a younger generation is to help them prevent this disease by actively doing what we propose in this poster. Youngster contribution will be a great power to eradicate and prevent this disease in elderly. ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
FIGHT THE PAIN !
! ! ! ! ! ! !
Osteoarthritis is a joint disease that mostly affects cartilage. Cartilage is the slippery tissue that covers the ends of bones in a joint. Healthy cartilage allows bones to glide over each other. It also helps absorb the shock of movement. In osteoarthritis, the top layer of cartilage breaks down and wears away. This allows bones under the cartilage to rub together. The rubbing causes pain, swelling, and loss of motion of the joint. Over time, the joint may lose its normal shape. Also, bone spurs may grow on the edges of the joint. Bits of bone or cartilage can break off and float inside the joint space, which causes more pain and damage. People think exercising with osteoarthritis could harm the joints and cause more pain, but research shows that people can and should exercise when they have osteoarthritis. Exercise is considered the most effective non-drug treatment for reducing pain and improving movement in osteoarthritis. Therefore, combining a few literatures we collected we present three kind of important exercise for people with osteoarthritis: exercise involving range of motion (also called flexibility exercise), endurance or aerobic exercise, and strengthening exercise. Each one plays a role in maintaining and improving the ability of people with osteoarthritis to move and function.
!
COME ON GUYS ! BE A PART OF COSINESS DEMENTIA ELDERLY !
Dementia is a generic term indicating a loss of intellectual functions including memory, significant deterioration in the ability to carry out day-to-day activities, and often, changes in social behaviour. There are five impaired symptoms of dementia. Dementia elderly experience with impaired of memory, communication and language, ability to focus and pay attention, reasoning and judgment, and visual perception. The most common difficult situations that can arise when supporting a elderly with dementia are how to relate to a person with dementia who is living a different ‘reality’ to yours and how to respond when they refuse assistance. Caregivers of dementia elderly often suffer from physical and emotional problems as a result of the stressful and burdensome caregiving process. As a young generation, we can take our part to caring the elderly with dementia. In this poster, there are some guideline how to care elderly with dementia called ‘Cosiness’ that young people can do for them. Make a elderly with dementia in cosiness situation is the main point of caring dementia. ‘Cosiness’ in our poster is an abbreviation and it is noted in note book that make us easy to remember and review again someday about dementia elderly guideline. COSINESS are abbreviation of consistent physical activity and daily routine; speak in clear, low, warm and respectful tone; introduce self when initiating contact, eye contact and touch when interaction; seat patient at small table in groups for meal; and select activities and tv/radio program according to abilities and interests. The elderly people is around of us. Dementia may could happen to our family or the other elderly which is they need our care. So come on guys, we can take our responsibility. Be a part of cosiness dementia elderly.
ALZHEIMER’S : CAN YOU REMEMBER ? !
Alzheimer’s disease is a progressive brain disorder of elderly people that gradually destroys a person’s memory and ability to learn, reason, make judgements communicate and carry out daily activity. This poster captures the process of alzheimer’s itself, where the mass of the brain gets smaller consistent with the age of the person getting older. The shrinkage of brain mass affects the drop of brain ability to perform activities such as remembering things, interpret incidents, and other activities, which makes the worse phase of this disease is when the patient loses his/her entire memory and eventually won’t even be able recognize his/herselfanymore. There are two reasons that make Alzheimer’s such an important issue and deserves special attention, first is that basically to treat someone that has alzheimer’s isn’t easy, it needs lots of patience and persistence in facing unpredictable situations with the patient, because these patients sometimes can seem to act normal, in meaning they’re able to remember things almost as good as if they’re not sick at all, but at other times, the patient can be seen very depressed at times when they’re not able to recognize other people around the him/her and even his/her own self in this case. The second reason is just as important, it’s that in several studies on alzheimer’s show that the cause of this disease is because the brain isn’t used to think or to act passive that often or in other cases can be caused by massive stress or depression. Because of that, we see by fully using the brain but in a relax way and not forcing the brain to work too much is expected to be a key factor to prevent this disease and reduce the number of patients in the future. So we describe alzheimer’s in this poster hoping that it can explain the process of alzheimer’s quite well and we also hope that the society and especially the youth to know better and be more concern of their self and to be more aware by implanting a better lifestyle in order to reduce the number of alzheimer’s patients in the future.
! ! ! !
MOISTURIZERS AS PREVENTION AND TREATMENT OF DRY SKIN IN THE ELDERLY Radius Hartanto, Liliani Labitta University of Tarumanegara
Skin is the outermost layer of a body; it serves as a protective barrier against dangerous stimulants from the environment. Thus it is essential for the public and physician to understand the importance of maintaining a healthy skin, especially among the elderly. Poor skincare among the elderly would result in several skin conditions with grave consequences, having a dry skin is one of them. Dry skin (xerotic) is a skin condition that shouldnâ&#x20AC;&#x2122;t be overlooked; it would enhance formations of wrinkles and scaly skin textures, increases the fragility of the skin, induces a sense of itchiness and sores, but most importantly a dry skin is highly susceptible to infections due to the formations of cracks and fissure along the skin. These consequences prove to be dangerous especially among the elderly. Through numerous amounts of researches and publications, it is stated that the uses of moisturizers would prevent the damage done to the skin by dryness, reduces the formation of cracks which improves the skinâ&#x20AC;&#x2122;s protective capability, and it would also improves the skin appearance.
FALLS Michelle Oswari, Monika Aprilyanti Atma Jaya Catholic University of Indonesia
The number of the Indonesian elderly population tend to increase every year. According to Badan Pusat Statistik Indonesia, the population of the elderly in Indonesia at 2010 is 18.57 million life, increasing from 2000 with 14.44 million life. And the life expectancy at present is considered to be longer than before. Falling is included as one of the Geriatric Giants. It’s a principal chronic disabilities of age that impact on physical, mental & social domains in the elderly. According to CDC, every 14 seconds, an older adult is treated in the E.R. for a fall. Every 29 minutes, an older adult dies following a fall. Falling is often left behind and underestimated, but it’s one of the most common leading cause of death in the elderly. Physiologic changes of normal aging may increase the risk of falls. Some changes input from the visual, proprioceptive, and vestibular systems, can cause balance instability. The other reasons are loss of muscle strength, changes in blood pressure regulation, age related changes in total body water and renin-angiotensin system play role to impairments in blood pressure regulation. Due to the significant decline of seniors’ abilities after a fall, it’s important to know how to prevent seniors from falling. Nevertheless, there are some difficulties when taking care of the elderly. Youth can take a part in management of falls in seniors. We can HINDER before they fall. It is by Help elders with difficulties, Install railings & bars at public places, Never stop encourage elders to exercise, Don’t forget to take elders for check up, Educate yourself & relatives for emergency, Raise awareness on how connected falls & significant decline in seniors’ abilities. HINDER before they fall!
AVOID OSTEOPOROSIS Gloria Teo, Jennifer E Dewantara, Santika Henny Atma Jaya Catholic University of Indonesia
In 2010, elders in Indonesia has reached 18.04 million of lives. This phenomenon has made Indonesia into the world top 5. Therefore, geriatric disease has become a serious issue and need more attention. Based on the national data statistics, the most common geriatric disease in this country is Osteoporosis, Heart Disease, and Diabetes Mellitus. The word osteoporosis means "porous bones". It is a disease in which the bone density and quality are so reduced that bone become porous and fragile. Osteoporosis appears due to an imbalance between new bone formation and old bone resorption. The body may fail to form enough new bone, too much old bone may be reabsorbed, or both. It occurs silently and progressively. Often, there are no clear symptoms until the first fracture occurs. According to Medscape Literature, the common symptoms are acute back/hip pain for 4-6 weeks, usually following a fall/minor trauma. Sometimes it is accompanied with muscle spasms around the back. In some cases, the patient remains motionless because he/she is afraid of a more worsening pain. The leading cause of osteoporosis is a lack of certain hormones, particularly estrogen in women and androgen in men. Woman, who is older than 60 years and during menopause with low estrogen levels, has a greater risk. Other factors that may contribute to bone loss include inadequate intake of calcium and vitamin D, lack of exercise, particular drugs/medication, or other bone disease. Osteoporosis usually results in vertebral (spinal) and hip fractures. Finally we came out with an idea called â&#x20AC;&#x153;AVOIDâ&#x20AC;?. It stands for Alcohol, caffeine and smoking which must be limited; Vitamin D consumption should be increased; Obesity must be countered through weight-bearing exercise; Increase calcium intake since childhood; bone Density must be checked regularly for an early diagnose. Let's take a step to AVOID osteoporosis!
PARKINSONâ&#x20AC;&#x2122;S DISEASE? WE DARE TO CARE Kirti A. Suharsono, Robert, Erika Indrajaya Atma Jaya Catholic University of Indonesia
Parkinson’s disease (PD) is known as a neurodegenerative brain disorder that progresses slowly and the symptoms take years to develop. A person’s brain slowly stops producing a neurotransmitter called dopamine. As a chemical messenger, dopamine is pretty similar to adrenaline, which affects brain that controls movement, emotional response, and ability to experience pleasure and pain. In PD patients, the brain contains almost no dopamine. Hence, it usually affects the ability to regulate movements, body, and emotions. It can be hard to tell if you have Parkinson’s disease, but there are 10 symptoms that can be found. Tremor or shaking, small handwriting, loss of smell, trouble sleeping, trouble moving or walking, constipation, a soft or low voice, masked face, dizziness or fainting, and stooping are the common ones you can find in most PD patients. Many people asked could PD be treated? The answer is there is no cure for PD. Medication, surgical therapy, or lifestyle modifications – more rest and more exercise are usually used to treat its symptoms. Nevertheless, there is no standard therapy for the disease itself, but only treatment based on the symptoms. There are approximately 60.000 Americans diagnosed with PD each year. Bring it broader; an estimated 7 to 10 million people worldwide are living with PD. Another fun fact is that men are one and a half times more likely to have Parkinson’s than women although there is still unknown reason. What about Indonesia? According to researches in several hospitals in Sumatera and Java, there are approximately 200.000-400.000 out of 210 million people are suffering from PD with average age above 50.
SUPPORTS ARE MEDICINE Erika Gracia, Ingrid Julia Atma Jaya Catholic University of Indonesia
Depression is a common problem in elderly but is often considered as an unimportant mental condition that does not require any treatment. In addition to it, 70% of people who suffer depression do not even realize that they have the disease. This condition makes only few people care. Nevertheless, this mental condition can affect the patientâ&#x20AC;&#x2122;s physical well being and increase the risk of other severe diseases. It may happen due to the presence of stressors, genetic factor, physical illness, low self-esteem, and problems in social life. Some physical illnesses that can cause depression are neuroendocrine abnormalities, neurodegenerative disease, and vascular depression. If a person suffers depression, they usually do not want to do anything and see anybody, but isolation and inactivity only make this worse, even can lead to major depressive disorder. To prevent it from getting worse, they need to receive the right medical treatment from professional healthcare provider, maintain healthy lifestyle, and make a good interaction with people around them. Most people think that depression as a disease can be healed by medication that they are too busy looking for the best medication and neglect the importance of support whereas the patient really need their presence and care. Moreover in some cases, the lack of attention and support may be the main causes of the depression itself. Besides it, giving support is the easiest way to help your loved one. So, letâ&#x20AC;&#x2122;s start supporting and together we can defeat depression!
BETWEEN FAMILY, APHASIA SUFFERERS LIVE HAPPILY Natasha Vinita Wardoyo, Emiliana Kartika Atma Jaya Catholic University of Indonesia
Aphasia is an acquired language disorder because of left-hemisphere brain damage, characterized by complete or partial impairment of language comprehension, formulation and use. This is commonly occurs in elderly with stroke or neurodegenerative diseases such as Alzheimerâ&#x20AC;&#x2122;s. Nearly three-quarters of strokes occur in elderly (people aged over 65). Risk of having a neurodegenerative disease also increases in elderly, though it is not impossible for youth to suffer such diseases. Facts above show that risk factors for aphasia increase with age. Even though a person with aphasia has difficulties in retrieving word, the intelligence is still intact. They want to communicate but can't find the words. This condition could degrade people quality of life out of frustration. It affects their job, relationship and social life. Research shows that eight out of ten people who suffer from aphasia become depressed. It is a serious issue if aphasia left untreated. Therefore, we find it important to raise public awareness of aphasia, through this poster, and also to share a way to communicate in dealing with aphasia. In the poster, we emphasize the word â&#x20AC;&#x2DC;familyâ&#x20AC;&#x2122;, as family members matter most to aphasia treatment. As the closest circle, they need family to understand and accept their condition. Family members, as caregivers, also enhance the role of speech-language pathologist in aphasia treatment.
DEMENTIA: UNDERSTAND, SUPPORT, & STAY ACTIVE Theodora Kristoforus, Glen Lazarus Atma Jaya Catholic University of Indonesia
This poster is created in aims to raise public awareness on dementia. Nowadays, dementia is a common disease in the elderly. However people often thought that eventually every elderly will forget things as a normal part of aging, not knowing that the pathologic process can be prevented. Thus people suffering from dementia are often neglected. Dementia patients often feel neglected and excluded from the community, while their family and friends donâ&#x20AC;&#x2122;t understand the suffering that they feel. Moral support is immensely needed for dementia patients, especially coming from their familiars. A higher participation from public to support patients with dementia is not enough. We can also prevent and reduce the risk of dementia by inducing a more active lifestyle against the common sedentary ways of the elderly. By applying the concept of â&#x20AC;&#x153;Brain? Use it or lose itâ&#x20AC;? we are training our cells to continue working against the pathological decay of aging. Sedentary lifestyle is not good for the brain. Keeping the brain active will help the prevention of dementia.
OSTEOPOROSIS: WE KNOW, WE PREVENT Fahreza Fajar Muharam, Michele Triandani Ludong University of Halu Oleo
Osteoporosis is a degenerative disease that common find in the elderly. Although the disease no longer rare to the people, it still received less attention from the society. Osteoporosis is a systemic skeletal disease, characterized by the decreased of the bone quality and density. It may causing bones become brittle and susceptible to get pathologist fracture. In this public poster, we try to explain along the increasing of the age, the bone density decreases slowly. It shows by the composition of the puzzle that was originally compose compactly, over the increasing of age the composition of the puzzle will be brittle and fragile. To avoid the premature osteoporosis we should begin to prevent it from young age by eating foods that contain a lot of calcium because calcium is an essential component for the preparation of bone density in young age. With a compact bone in young age then we can slow the bone loss in old age. But when osteoporosis was happened in our parents, we can advice them to avoid the activities that can be the disease complication and still consume calcium to fulfill the daily calcium needed.
DEMENTIA: ERASE EVERYTHING Muh. Afhal Ruslan, Amalia Nur Azizah University of Halu Oleo
Along the increased the number of elderly population in developing country, the number of dementia was increased. The problems that exist in society today, especially in developing countries such as Indonesia are the occurrence of social change. More and more people just do not have children or a big family, in charge of care, financial support and shelter. Migration to big cities is also other factors that break down the traditional family structure. Actually, people with dementia need attention and care from society especially from their family. This public poster shows the people with dementia. Their dementia will erase their memory. They canâ&#x20AC;&#x2122;t recognize their self and the other people. They can loss their cognitive function, concentration, social ability and many others. Their dementia can loss everything. As a young generation, we have a responsibility to aware for this condition. Start from our family and continued to the society. What can we give for them? Care and attention! It is look easier and simple, so we must prove that we can do it. Dementia can erase everything they have, but not our concern for them.
PARKINSON DISEASE Mardhiyah Nur Dini, Reza Agustiantwo Putra, Rizka Karina Mayang Sari University of Muhammadiyah Palembang
The process of aging is not something that happens only in the elderly, but a normal process that took place since the maturity and death ends. However, the aging effect is usually seen after the age of 40 years and above. Parkinson is a disorder of brain function which is caused by neurodegenerative processes associated with the loss of substantia niagra cause an imbalance of the neurotransmitters between dopamine and acetylcholine in their body. The exact cause of Parkinson's disease is still not known, but several factors such as the aging process of the brain, stress, infection, alcohol, head trauma, and smoke into the causes of Parkinson's disease. Clinical symptoms of Parkinson's disease is TRAP: Tremor, Rigidity, akinesia, postural abnormality. Tremor is a symptom that occurs in the form of movement from the top to down. Patients usually feel shaky at the upper extremity. This usually occurs at rest. Rigidity is the second symptom where muscle get stiffness so that when the patient walks looks like dragging. Third, akinesia is the lack of movement or facial expression that looks like a mask patients and patients also salivate when swallowing something. The last, postural abnormality which the patient's body posture leaning slightly forward that causes the patient is slow to move or walk. Management of patients whoâ&#x20AC;&#x2122;s affected by Parkinson's disease is giving drugs to balance the use of dopamine and acetylcholine in the patient's body, those are levodopa, carbidopa.. Preventions of this disease are trying to avoid trauma to the head, avoiding to consume alcohol, trying not to think much, having a healthy life and staying away from cigarettes. The role of the family is really needed in the rehabilitation of Parkinson's disease. Although, Parkinson's disease does not cause death but the patient is difficult to carry out their daily activities. "One respect can change the world"
COPD, LET THE LUNGS AGE GRACEFULLY Paulus Mario Christopher University of Pelita Harapan
Chronic Obstructive Pulmonary Disease (COPD) is a chronic irreversible or partial reversible inflammation process that causes narrowing of the small airways and structural changes of the lungs. It consists of chronic bronchitis and emphysema. COPD is one of major worldwide public health problems; especially elderly who are more prone to the irreversible and harmful effect of the disease. According to Global Burden of Disease1, more than 3 million people died of COPD in 2005, which is equal to 5% of all deaths globally that year. Whilst according to the Survei Kesehatan Rumah Tangga/SKRT (Survey of Household Health) 19922, showed that asthma, chronic bronchitis, and emphysema, ranked 6 out of 10 leading cause of death in Indonesia, it is often undiagnosed and leads to under treatment of the disease. Factors that influence development of COPD and progression are as follows; (1) Cigarette smoking which contribute as leading COPD risk factor, (2) Alpha-1 antitrypsin deficiency, (3) Age and gender, (4) Lung growth and development, and (5) Exposure to particles; such as cigarette, marijuana, passive smoking, etc. The burden of COPD leads to a life-long therapy, management, and support. Nevertheless, adverse effects from the medications may never be neglected, especially for elderly. In this poster, firstly, the poster is to raise awareness, bring about concern of people, and to promote healthy lifestyle against COPD. Secondly, I would like to introduce the management and prevention, which is to stop smoking. Thirdly, I would like to explicate the motto for COPD, which is â&#x20AC;&#x153;Let the Lungs Age Gracefullyâ&#x20AC;?. This motto emphasize on the aspect of life of human being, especially elderly, as we should be able to allow people to always enjoy their life and to allow our organs to grow old together with the rest of the body in righteous manner. Lastly, I share a brief effects of smoking on the lungs as it would cause inflammation on the lungs tissue and to acknowledge the public that COPD is something that could be treated and overcome if the main risk factor is removed. Many people misunderstood COPD, the main risk factor, and therefore underestimate its effects on health.
WHEN STROKE STRIKE, ACT FAST! Ernestine Vivi Sadeli, Paulus Mario Christopher University of Pelita Harapan
Around 400 B.C., Hippocrates recognized stroke as an apoplexy. Apoplexy is bleeding within internal organs and results with accompanying symptoms. In 1600, only then the medical communities understood that strokes are “brain attacks” associated with blockages or bleeding in the brain. Today, based on the global measurements undertaken by the WHO, it is revealed that stroke is the third highest cause of death, and the leading cause of adult disability. In general, within five years of a stroke, over half of patients aged greater than 45 years will die and many of them will have disability. In this country people suffer 795,000 strokes each year, 610,000 of which are first strokes. Stroke occurs because of a sudden failure of the brain to receive the oxygen and nutrients it needs to thrive. It can happen to anyone at any time. Since stroke is an emergency condition, early treatment is extremely important. The chances of survival are greater when treatment begins quickly, so ACT FAST! Delaying treatment may cause a permanent disability. In this poster, we would like to share our motto for overcoming stroke, that is “prevent, treat, and beat”. It is preventable when the public has knowledge of the causes and symptoms of a stroke. It could be treated successfully when the causes are found. Lastly, it could be eradicated fully when health associations take full responsibility to help creating the awareness for the general public on this cerebrovascular disease. Prevent means that stroke is a preventable disease. But at the same time, it is also treatable disease. And also social support is the most important thing to accompany and increase patient’s quality of life. Our poster share brief description on stroke, the required behaviors or actions to prevent it, and the clinical recommendation on how to detect its symptoms quickly. Our objective is to provide a general guidance on the effectiveness of specific interventions such as Life’s Simple 7. Such information will help a wide range of general public to concern with individual and community care, to promote a healthy lifestyle, propose for holistic health policies and guidance on its early treatment. The long term goal for our country is to establish a national, integrated, and community-based system to prevent, treat and beat stroke from all society.
STAY CONNECTED Raissa Metasari Tanto, Afandi Charles University of Padjajaran
Depression, one of mental health disorders commonly found in the elderly, is defined as feelings of sadness, loss, angger, or frustation with interfere with daily life for weeks or longer. This mental disorder often goes unnoticed and untreated since many people believe that depression is normal part in aging and social transitional stage. Although depression appears in elderly after some recognized situations (the death of loved ones, retirement, increased isolation, and loss of independence), it can also be related to some physical diseases, such as thyroid disorders, heart disease, cancer, stroke, parkinson, and dementia. Alcohol and sleeping pills overuse can worsen depression in older people. Furthermore, women in general are twice as likely as men to become seriously depressed. We can recognize depression in older people as having memory problems, confusion, social withdrawal, loss of appetite, weight loss, vague complain of pain, inability to sleep, irritability, delusions and hallucination. Whereas clinical and psychiatric interview are the important aspects to diagnose depression, talking with their family members or close friends are often useful in reassuring the mental condition of elderly. Luckily, outcome of treatment for depression is good. Antidepressant medication and electroconvulsive therapy are available to treat this condition, However, psychosocial supportive treatment plays an essential role in the care of elderly dealing with their life situations. Interpersonal communication helps the elderly to recognize the conflict area causing the depression, such as unresolved grief due to loss of beloved people or role transition as elderly in social community. Communication with respect and empathy also helps them to examine their thoughts and feeling regarding these situation and resolve the conflict area in order to resolve the cause of depression. Therefore, good communication between elderly and their surroundings would diminished depression and enhance their quality of life.
DEMENTIA: KEEP YOUR BRAIN YOUNG Angeline Bongelia Friska, Grace Elizabeth Claudia, Jessica Gunawan University of Kristen Krida Wacana
Dementia is a declining of mental ability such as severe loss of thinking ability, memory, and reasoning. All of them could affect the person's daily functioning and activities. Dementia inflicts parts of the brain, which involving learning, memorizing, decision-making, and language, affected by one or more of a variety of infections or diseases. Dementia is not a part of normal ageing. One obvious reason is that most elder people do not have dementia. We have some way to reduce risks of dementia. First, physical exercise. It will maintain the brain function as well. Second, keep the mind active. It will stimulate mental activity and memory training. All could delay the onset of dementia and help decrease its effects. Third, avoid stress. Stress could be a trigger to dementia. Fourth, active in social life, it will delay the onset of dementia and reduce its symptoms. Lastly, have a sufficiently rest. Once infected, dementia could not be cured permanently. Medicine may only treat the patients to have a better quality of life. Medicine may help to improve mental function, mood and behavior. Support and counseling are important for people with dementia. Person in the early stage of the illness should seek emotional support from family and friends, but sometimes, itâ&#x20AC;&#x2122;s difficult to do all the prevention and management for the disease, because elder people with health and vulnerable condition tend too lazy to do activity. Elderly people also have high ego so itâ&#x20AC;&#x2122;s hard to listen the advice from others. Everyone could participate to reduce this problem, we need to take care of people around us, help them when we see them struggling. They really need our support and understanding about their condition. So now this is our responsibility to reduce dementia in elderly people. Letâ&#x20AC;&#x2122;s fight against dementia!
EATING NUTRITIOUS FOODS IN ORDER TO PREVENT OSTEOPOROSIS Franklin Wijaya, Grace Elizabeth Claudia, Randy University of Kristen Krida Wacana
People these days tend to have everything in instant way including food, and thatâ&#x20AC;&#x2122;s why junk food become the option to get a good taste food in the fastest way. Junk food may taste good, but it is lack of nutritions for the body.In Indonesia 2 out of 5 people are at risk of osteoporosis, this is caused by low consumption of milk, and increased consumption of unhealthy food.Osteoporosis is an asymptomatic disease which cause bone fragility that can lead to bone fractures. Osteoporosis usually found on people age above 50 and especially women after menopause, on the age of 30 the Bone Mineral Density(BMD) have reached the peak. Itâ&#x20AC;&#x2122;s different in everyone based on their exercise habits and diet. People with bad diet and bad exercise habits tend to have lower BMD than people with proper exercise and good diet. Osteoporosis can be prevented from young age until 30 years old by reaching high BMD, in order to reach it we need to eat nutritious food especially food with high calcium and vitamin D like milk,bones,cheese,fish,milk,etc. Exercise regularly to help reaching high BMD especially for people under 30, decrease the loss of BMD, and to maintain BMD, the best exercise for bones are weight bearing exercise such as jogging, walking, weight lifting, and many other exercise that forces us to work against gravity. Being exposed to sunlight is good way to get vitamin D, because vitamin D is proven beneficial for increasing calcium absorptions. With a high intake of calcium and by the help of regular exercise since adolescent,everyonecan prevent osteoporosis.
CARING ELDERLY INCONTINENCE Ade Saputri, Putri Raudina Alifah, Vindy Andana Reksa Putri! University of Gadjah Mada
Based on data of UNFPA Indonesia, the elderly percentage in 2035 is 15.8% of population or 48.2 million. High numbers of elderly also come with the high percentage of health concern because elderly are very susceptible. Incontinence especially about urine is one of the most disease attacking elderly and it is one of â&#x20AC;&#x2DC;four giantâ&#x20AC;&#x2122; disease. Incontinence is involuntary loss of continence. There is many causes for an elderly get this illness not just because aging process. Changes in the elderly body make them no longer to be able to hold their urine. It can be anatomical or physiological changes, the neural or systemic disturbances also make a sense to cause incontinence. However, with this illness elder people will become more dependent. The more depending the more depressing because they cannot act the way they want. They will need help from others. This is the family role as the one they can trust. Family should act positive to this condition and actively caring. Family should be giving elderly support and keeping an eye to maintain their health. Actually this illness can be treated clinically to improve their condition but, The most important thing about this condition is how the people around treating them. It is all about action and reaction. If the people around is caring, they will just fine. Older people are very timid, sensitive, and fragile. So, the simplest way to help them is caring. Family care and love are very important thing to them. Every communication happen is always count for elderly. Treatment will be effective under these positive environments. So, just give them an action and theyâ&#x20AC;&#x2122;ll give us a reaction. After all, preventing is better than treating. Have a good lifestyle, like doing exercise regularly, eat well, drink enough water, avoid alcohols, and avoid caffeine.
MORE CARING, LESS SUFFERING Dery Rahman A, Nur Rahma Rizka P. A, Rosyida Avicennianing Tyas University of Gadjah Mada
Millions people in the world, or about 1% of world population suffer from Parkinson’s disease. In Indonesia, 876.665 people had been diagnosed as Parkinson’s disease as of 2010. The number of total death caused by this disease in Indonesia ranks the 12thin the world(Novianidkk, 2010). Parkinson’s disease is a chronic and degenerative neurological disease. This means that the symptoms continue and worsen over time, sometimes starting with a slight tremor in just one hand. Parkinson’s disease usually affects people over the age of 50, but in some cases young people can also suffer from it. The primary symptoms of Parkinson’s disease are involuntary tremor of some areas in the body, difficulty in initiating movement (bradykinesia), rigidity or stiffness of much of the limbs and trunk, postural instability that leads to poor balance and falling, as well as other motor symptoms like dysphagia (difficulty in swallowing), speech disorders, gait disturbances, and much more. As the disease progresses, this symptoms may begin to interfere with daily activities. Parkinson’s disease patient needs more times than other people to do simple activities such as walking, taking food with spoon, buttoning shirt, etc. (Guyton, 2010) Until now, there is no cure for Parkinson’s disease, but a variety of treatments provide dramatic relief from the symptoms. The purpose of this poster is to raise people’s care for Parkinson’s disease patient. Even though this disease doesn’t have a cure, people can help Parkinson’s disease patient by taking care of them, trying to help, and understanding them. We hope people can help Parkinson’s disease patient with simplest habits. We might not be able to cure them, but we can at least decrease their burden.
YOUR HAND IS YOUR HELP Priscillia Imelda, Nisrina Maulida Rozanti, Lala Sri Fadila University of Gadjah Mada
According to WHO (World Health Organization), between 2000 and 2050, the proportion of the world's population over 60 years will double from about 11% to 22%. The absolute number of people aged 60 years and over is expected to increase from 605 million to 2 billion over the same period. Elderly was considered as golden period where the diseases begin to come.It is important to prepare health providers and societies to meet the specific needs of older populations. RISKESDAS (Riset Kesehatan Dasar) result in 2007 showing that the most widely disease pattern in elderly is joint disorders, following by hypertension, stroke, and diabetes mellitus. These diseases are mostly degenerative disease. Many people assume that the older people were weak, vulnerable, and could not do a lot of activities. Some of them sometimes aside older people from the social world. From the data before, we conclude that joint disorder can be a reason why older people are difficult to do activities. Joint disorder causes older people difficult to walk even it could be immobilization or pneumonia if they often fall. Activities that considered being easy for young people are not the same as older people do with this condition. Therefore, older people need someone helps. From this poster, we want the societies, especially family, to caring this older people whom difficult to do their activities and for preventing the disease severity. One activity cannot be necessarily done much less two or more. We only have two hands. Sharing them for helping.
DEMENTIA, “RECOGNIZE, DO, SOLVE” Ririn Enggy Yulianti!"Yessika Agasa" University of Gajah Mada
According to WHO in 2012, dementia is the health priority. This abnormalities part of ageing already happened in 35.6 million people in 2012 and 7.7 million new cases every year. It is a syndrome in which there is decreasing of cognitive function which affects the ability of thinking, learning, calculating and the other. Dementia also known for the disability that happens in elderly. Dementia is the important thing that we have to solve, it affect many sectors in life. Social, economic, furthermore their human right which is frequently violated if there isn’t good quality service for them. This poster is about our responsibility to solve the problem. We have to pull the rope and release the smiling grandpa and the brain. Its mean that we have to solve and fix the problem to create more smiles in them. And one of the problems is Dementia, which is especially attack the brain. We have to pull it, it can’t release by itself, it mean that we have to do something about it because it can’t be solve without our effort. To know what we have to do, we have to recognize the case and our purpose is solving the case. So that’s why our title is “Recognize, Do, Solve” We hope the people will have an intention to recognize dementia, they will know and have more awareness for dementia. So they will do the act that they can do even thought a simple thing like caring, giving attention etc. And our goal is persuade people to solve dementia.
DEMENTIA: KNOWING, CARING, AND LOVING Widha Cahyaning Yuniarti, Nurul Hanifah Rahmadani University of Gadjah Mada
Dementia is defined as an acquired deterioration in cognitive abilities that impairs the performance of daily activities. It is a syndrome caused by various brain illnesses. Based on data estimation from the World Health Organization, there are 35.6 million people with dementia worldwide. The total global annual cost was estimated at US$ 604 billion. The most common cognitive ability lost with dementia is memory. Beside that, the other mental faculties such as language, visuospatial ability, calculation, and problem solving as well as neuropsychiatric and social deficits also arise in many dementia syndrome resulting in depression. The signs and symptoms are various. It can be merely forgetfulness that is often overlooked in the early stage of dementia to total dependency and inactivity in the late stage of dementia. Even though there is no treatment available to cure or to change the course of dementia, we can improve their quality of life. By early diagnosis, we can optimize their physical health, cognition, activity, and well-being. However, there are stigmatization and barriers to the early diagnosis and care caused by lack of understanding about dementia. We want the public to know, to care, and to love. By knowing about dementia, we can have a better understanding and raise our awareness. Then, everyone can take their own roles as caregivers and giving their utmost support and love to people with dementia. Let us make them smile by knowing, caring, and loving!
DRINK MILK BEFORE YOU DOWN Alfina Alfiani, Aliatunnisa. University of Muslim Indonesia.
Osteoarthritis is a chronic degenerative joint disease with a high prevalence among older people. The prevalence of radiological knee OA in Indonesia is quite high, reaching 15.5% in men and 12.7% in women. Because of the relatively high prevalence and it is chronicprogressive, OA has a socio-economic impact in the developed and developing countries. It is estimated that 1 to 2 million elderly people in Indonesia suffer disability because of OA. The predominant symptoms are pain, a decrease joint range of motion (ROM) and stiffness, periarticular muscle weakness and atrophy, joint effusion and swelling, and physical disability. Commonly, OA is characterized by structural changes of the entire joint. Partial to full thickness loss of articular cartilage, subchondral bone sclerosis, osteophyte formation, and thickening of the capsule are the typical clinical and radiological sign. Moderate physical activity levels appear most beneficial to prevent cartilage degeneration in patients at risk for osteoarthritis. Lower impact sports, such as walking or swimming, are likely more beneficial than higher impact sports, such as running or tennis, in individuals at risk for osteoarthritis. Obesity and overweight have long been recognized as potent risk factors for OA, especially OA of the knee. Numerous studies have shown that knee injury is one of the strongest risk factors for OA. Severe injury to the structures of a joint, particularly a transarticular fracture, meniscal tear requiring meniscectomy, or anterior cruciate ligament injury, can result in an increased risk of OA development. Dietary factors are the subject of considerable interest in OA. One of the most promising nutritional factors for OA is vitamin D. without sufficient vitamin D, bones can become thin, brittle, or misshapen.
NUTRITION EFFECT AS PRIMARY MEDICINE AND ANTI AGING FOR QUALITY OF GERIATRIC LIFE IN INDONESIA Hesti Herlinawati, Ilham Henintyo, Sandi Yudha, Gita Kristy University of Pembangunan Nasional “Veteran” Jakarta
Protein-Energy Under-nutrition (PEU) is a clinical syndrome characterised by weight loss associated with significant depletion of fat stores and muscle mass. There is a continuing spectrum of under-nutrition from mild PEU to that of visceral organ failure resulting in gross peripheral oedema. PEU is a metabolic response to stress that results in a significant increase in protein and energy requirements to maintain homeostasis. Inadequate nutrient supply primarily affects organ systems with rapid cellular turnover and can develop within 2 or 3 days of inadequate intake. Acute confusional states are often seen in PEU and are related to dehydration. Multiple vitamin and trace element deficiencies may also occur. There is no agreed gold standard definition for PEU but there are physiological and non-physiological factors that contribute to the development of PEU.
THE THIEF OF SIGHT Dian Riftya Rahmawati, Dina Savita Marchelly, Desak Made Nugrahartani University of Hang Tuah
Eyes is one of the important sense of the body. They play important role in our daily activity. But as we grew older, eyes loss their function. Most of elderly complain a incapability to see. Many of them had experienced sight disruption, it’s a condition which characterized by dropped vision or visual field reduction, furthermore it can lead to blindness. One of the causes of blindness is glaucoma. Glaucoma is a disease which can damage the optic nerves. It is due to the increasing of intraocular pressure (above 20 mmHg) which damage the optic nerves. You are at increased risk of glaucoma if your parents or siblings have the disease or you are diabetic or have cardiovascular disease. The risk of glaucoma also increases with age. Therefore, as young generation as well as a medical student, who care about health issue, feel obligated to reduce the number of blindness caused by glaucoma. Here we would like to proclaim our movement : AWARE, EXAM & CURE (AEC). AWARE means spread the awareness of glaucoma towards the elderly. Help them to know, learn, and realize that they’re in a risk of glaucoma or not, aware to live healthily and aware the danger of glaucoma. Second is EXAM, since glaucoma is The Thief of Sight, most people who have glaucoma (open-angle type) feel fine and do not notice a change in their vision at first. It develops slowly and sometimes without noticeable sight loss for many years. Everyone should check their eyes condition at regularly, to find out if there’s any eyes problem. Lastly CURE, by the time a patient is aware of vision loss, the disease is usually quite advanced. Vision loss from glaucoma is not reversible with treatment, even with surgery. If glaucoma is detected during an eye exam, your eye doctor can prescribe a preventative treatment to help protect your vision and treat the underlying disease. By supporting AEC Movement, we can play our role as young generation and help those who need our assistance.
WHERE IS MY GLASSES? Helviansyah El Farizqi, Hamidia Maulaningtyas, Muthya Shinta Devi University of Hang Tuah
Growing old is certain. The organ function will be weakening and degenerating slowly, including the brain. The brain will be unable to recall any detail thing, Dementia. What’s dementia? How dangerous that dementia is? And what’s the correlation between dementia with youth responsibility? Dementia generally is a brain disease that decreases the ability to think and remember such that a person's daily functioning is affected. Other common symptoms include emotional problems, problems with language, and a decrease in motivation. The prevalence of dementia base on Alzheimer’s Disease International (ADI) estimates that there are currently 30 million people with dementia in the world, with 4.6 million new cases annually (one new case every 7 seconds). Now all of us know that the physical and emotional demands of caring for someone with dementia can be high. As the amount of attention that is needed is increasing, more time and energy is required from the care-giver. The big question is, who should be responsible for this case? The answer is absolutely it should be YOUTH RESPONSIBILITY. As a young and medical student we have to put more attention to the people who suffer with dementia, especialy when this case spread arround our family. Be a part of their memory, be a good guider for them and make such kind of comfort condition to them with huge love, add some colors to make a “rainbow” for their life, and. That’s all of thing we can do as a young generation.
AGAINST RHEUMATISM FOR BETTER FUTURE Faradina Nabila Indrajaya, Nur Rahayu Ningrat University of Jenderal Ahmad Yani
Rheumatism is a group of diseases that affect millions people. There are more than a hundred rheumatism diseases. The most common rheumatism disease is orteoarthritis, that known as rheumatism itself by many people. It affects more than 20 million people in the world. The prevalence is 33% in USA and 23,6â&#x20AC;&#x201C;31,3% in Indonesia. It is a kind of degenerative disease, so itâ&#x20AC;&#x2122;s very common in elderly. The biggest problem of this disease is the effect to mobility. So, it will be wise to prevent this disease. Our objective is to prevent this disease by letting people know its cause, symptom, and therapy. There are many things that can cause this disease, such as abnormal blood circulation infection, stress, obesity, and, wrong body positional. People with rheumatism will feel pain and stiffness of the joint that will affect their mobility and daily activity. Therapy of rheumatism are lifestyle changes and medication. Lifestyle changes to against rheumatism are exercise and eat healthy food, such as fruits and vegetables. ! !
? Photography
I AM WITH YOU WITH THIS Lidya Oktaviani Siauw Tarumanagara University ! !
Dementia is the term used to describe group of diseases that affects the brain, starting from the way of thinking, behavior, and abilities for daily functioning. Some brain cells stop working, losing connection with other brain cells and die. The most common sign of dementia is the decreasing of cognitive skills, especially recognizing. It is generally found in geriatric patients. Dementia is diagnosed when 2 or more cognitive functions are interrupted, including memorizing skill, speaking, understanding information, and paying attention. People with dementia may experience changes in personalities and difficulties in controlling emotion. One of the most frequent diseases of dementia is the Alzheimerâ&#x20AC;&#x2122;s disease. Placing a member with dementia into care must not mean to stop family life. Family involvement can improve patientâ&#x20AC;&#x2122;s quality of life by the familiarity and linking the past. Without cooperation between caregivers and family members, an appropriate care may be difficult. Close family plays an important role in taking care of a member living with dementia. Research says that the outcomes for people with dementia improve when families stay involved with their loved ones, as they know the unique spiritual, ethnic and cultural background of patient. Being together with close family also helps suspend Alzheimerâ&#x20AC;&#x2122;s diseases and other dementias.
! !
DELAYED RETIREMENT! Chintya "#$%!&%'%!(%#)*+,-!./,0123,#'!*4!5/6*/13,%!
! ! ! ! !
The World Health Organization estimates that 200 million of the 355 million people older than 65 years are in developing countries. Indonesia as one of such countries is supposed to be aware about this issue. Moreover, it is stated that the elderly in Indonesia are more vulnerable and are in need of more respect, care, and also support. Unfortunately, Indonesia has numerous other issues beyond the elderly problem. The government is more focused on children and maternal health. Hence, health care for the elderly is often neglected. As people who cannot afford their cost of living themselves, elderly need more attention from their families, communities, and also the government. Based on Statistics Indonesia (Badan Pusat Statistik) data in 2011, it is stated that 45,41% elderly in Indonesia is still struggling to fulfill their cost of living. As pictured in this photograph, this old man is a fisherman in Jakarta. I can cogently say that this old man is not supposed to work anymore considering his age and his capability of doing his daily activities. His physiologic changes make him more vulnerable to illnesses. Through this photograph, I would like to encourage us to broaden our perspective about the community around us. Aging is inevitable and delayed retirement in developing countries is hard to avoid. All we can do is keep this population healthy in order to reduce their burden of life. It is important to give support and care financially or by establishing better communication with them.
! ! ! !
! ! ! ! !
SMILE CAN BE AN OPTION Chici Endah Purnamasari, Indah Puspitasari Univesity of Halu Oleo
Smile is an expression that shows the greatness of spirit and broad-mindedness. Smile is also a mental and psychological therapy, our effort to resist the pressures that we have face. With smile, without realizing we are trying to entertain ourselves from any problems. With smile, unconsciously we treating the collapsed mental at once trained to be more rigid. Smile with intention and prayer in grief and distress is the best medicine for us to find a solution and get out from the psychological pressure and indirectly provide drugs to people affected by the stress and for those who have many problems in their life. This photographer show us, how the youngest can enter and change the older world with her attention, that showing in her smile. Relieve their psychological stress that can accelerate the generative process. What should we do when we see an elderly in a complicated problem? Itâ&#x20AC;&#x2122;s our responsibility to enter in their world and make them more comfortable. When many drugs are contraindicated due to old age, a smile can be an option. ! ! ! ! ! ! ! ! ! ! ! ! ! ! !
SOCIAL ACT: TIME FOR CARE
Nadiah Nurul Ikhsani University of Padjajaran
It is fortunate that lately, Social Act is often being carried on many occasions as one of its highlights, and why it is? Social Act is a chance that many can experience, moreover us as medical students, to interact with people around and if possible, help them. According to WHO in 2012, for the first time, in five years ahead there will be a higher number of geriatrics above 65 years old than infants under 5 years old, and what we can do following to that information is to ensure the well-being of geriatrics, by that means, ensuring their health. United Nations stated that later on, in developing countries, people donâ&#x20AC;&#x2122;t die because of communicable diseases, but because incommunicable diseases, say stroke, heart failure, or chronic pulmonary diseases, and that is the main underlying reason for bad health condition for most geriatrics, as WHO stated. By Social Act, we can prevent and promote their health, by checking their current condition, giving them education about their current health and somehow, we can promote their wellbeing for the better. Sometimes, what they need the least is being cared for, and aside from all stated health problems of geriatrics, loneliness can also be the underlying cause that can manifest in worse health conditions.
DEALING WITH GERIATRIC’S PATIENT MEANS RESOLVING THEIR PROBLEMS HOLISTICALLY Eifraimdio Paisthalozie University of Krida Wacana Christian !
! ! ! ! ! ! ! ! !
Geriatrics is a branch of general medicine whose focus in treating the illness in the old age based on the clinical, preventive, and social aspects of the illness, without forgetting that the old-age patients are having a special condition that may give different outcomes compared to the young. Many challenges will arise from dealing with old-age patients, such as the patient’s fragility, the complex co-morbidity, patient’s response to the treatment, and the patient’s compliance which usually decreases the treatment’s outcome. In addition, old-age patients often present with subtle clinical manifestation along with their several chronic illness which may blurring the real condition they’re having. And this, surely will affect the clinicians to work even harder to establish the diagnosis and starting the most appropriate treatment. Dealing with geriatric’s patient isn’t a simple thing, sometimes the treatment itself could complicate the illness therefore, we should consider it well. I photographed the eyes of one of the old-age patient I often meet. She’s having her old days accompanied with diabetes mellitus and its multiple complication, chronic kidney disease and still undergo routine insulin injection to maintain her blood glucose. She has been through a lot of clinicians, procedures and medicine in order to add more years to enjoy her old days. Oftentimes, depression and regret come to her and torturing her. But again, and again I see those light of hope in her eyes that oneday she’ll enjoy her last minute of life in a peaceful state. And I want to spread this hope to every single old-age patient to keep holding on whatever burden they might be dealing, now. That’s why I give the title of my photo “Hope in the Eyes of Elderly Patient." ! ! ! ! ! ! ! ! !
NO TITLE Adhe Ikmaynar Puteri University of Muslim Indonesia
Different with the stigma in society, that the elder people should be reducing their activity, its actually worsened their health condition and lowering their confidence. By doing some light exercise or activity in the morning regularly will help to maintain their health, and avoiding them from degenerative diseases. Because exercising also can help to slowing down the aging process, maintaining enough blood flow through the body preventing hypertension, strenghten the muscles and joints , strenghten the heart muscles preventing heartd diseases, reducing stress, also for the overweight elder people it can reduces their body weight which can help them to avoid getting disease such as osteoarthritis ot heart disease due to the obesity problem. In some studies its also said that exercising regularly can increase the amount of oxygen flow to the brain that can help to maintain the elder people's ability to memorize things, which usually decreases as they grow older. But one thing to be noticed is the type of exercises the suits the elder. The exercises must be safe, not too hard or demanding too much energy or may cause any injury because old people are quite easy to feel exhausted or get injured during exercises. The exercises that are safe for them for example, bicycling in a smooth road, aerobic dance, walking, or swimming. Or even just a regular chores like gardening, or cleaning the house. Stretching is also very crusial for the old people before they start the exercise to prevent any muscles or joints to be injured. All of this of course must be supported by people around them, friends, family, and neighbors. Because the moral supports will help the old people to feel more confidence and care about their health.
WHERE IS MY GLASSES? Quri Meihaerani Savitri University of Hang Tuah
She is my grandmother, i snap this picture when she want to read her book then ask me “Where is my glassess?”. Well, her glasses is right on her head. She is 80 years old and forgot almost in anything. Like did she have a lunch or not, did she already take a pills or not, talking the same matter repeatedly and start to not recognize her neighbor. Dementia (Pikun in Bahasa) usually occurs in individuals who are 60 years and older. The total number of people with dementia worldwide in 2010 is estimated at 35,6 million and projected to rise to 71% by 2050. Many people think dementia is a common abnormality that affect the elderly. But in fact, according to WHO International, dementia is not a normal part of ageing. Dementia is a syndrome, usually of a chronic or progressive nature, caused by a variety of brain illnesses that affect memory, thinking, behaviour, and ability to perform everyday activity. This “Forget Syndrome” seems not harmful. But imagine your grandmother walking around then forget her way back home and the bad people take an advantage of her.
That could be
dangerous. Caring for a loved one with dementia poses many challenges for families. Not only difficult to remember things, dementia also can cause mood swings and even change a person’s personality and behavior. Sometimes it could be difficult dealing with dementia especially in communication. Best thing you can do is being their friends that understand. Listen them with your ears, eyes, and heart even they just talking repetition old stories. Set a positive mood for interaction and get her/him attention so she/he could understand and listen to you, and don’t forget to use simple word and talk slowly when you ask her/him.
STAY POSITIVE AND STAY ACTIVE Christopher Adhisasmita Yandoyo University of Trisakti
This is the photo of 75 years old elderly siting in her bed while reading a book and hearing her favorite songs in the radio, keeping aware of any mosquitoes flying around her, and placing her favorite books, mobile phone, and notes around her. As shown in the photograph she looks great for her age wearing black blouse and batik like leggings. She looks like having a good quality time of herself doing some stuff she like. The elderly members of our communities are some of our greatest assets. They have seen the roar of change, the upset of recession, and the power in our humanity at work. They are one generation that has really unique behavior and style because of it. Sometimes they are moody, and sometimes they are so calm and so quiet, and sometimes they like to have a lot of conversation with other people and family members around them. They are experienced members of community who needs special attention and recognition to feel like they are still one of them and can actualize themselves like what they want to do and want to be. The message that we are trying to spread through our photograph is to open peopleâ&#x20AC;&#x2122;s eyes that we as young people need to ENCOURAGE the elderly to stay doing some positive activity like reading some books, communicating to society through social media, having an agenda for living and stay active every time and everywhere, and having some positive thought because it will really help them to SIGNIFICANTLY reduce their possibilities of having an Age Associated Memory Impairment (AAMI), Mild Cognitive Impairment (MCI), even having Dementia (decreasing in cognitive ability and behavioral skills) caused by less stimulation and releasing of stress factor to the brain. Stay Positive and Stay Active Grandma and Grandpa!
I NEED MONEY TO STAY ALVE Ayang Rashelda Maulidinia University of Trisakti
Finding older people working in our community is not a new thing. We can find it in every economic level. Some older people work as lecturer, entrepreneur, or even some of them work as cleaning service or trading like you see in this picture. But have you ever think how far we can tolerate older people who go to work? Elder mistreatment is not a familiar word but it is familiar for us to do. There are many kind of mistreatment, like physical abuse, neglect, financial abuse, emotional abuse, etc. Something that surprise us is family or care giver, who live together with older people and have direct interaction with them, is the most common doer. This is a picture about an old man who trading the crackers from one place to another. He is blind. You can guess it from his appearance, using black eyeglasses and a stick as a guidance for him to walk. Every people who see him feel become sympathy then buy his crackers. No sad feeling from his face. He always smile as long as he walk. It is okay to let people like that to work as long as there is no finance abuse behind it. We call it finance abuse if there is a family or his care giver who needs money then push older people to work and they donâ&#x20AC;&#x2122;t get any profit from that. Pushing older people to give their money to fulfill a familyâ&#x20AC;&#x2122;s daily need also called finance abuse. Letâ&#x20AC;&#x2122;s care about elder mistreatment. If we find that in our community, we have to make a report to police and Komnas Lansia (National Commission of Older People). Every older people have their own right to get their successful healthy aging.
MORE AGE, MORE WATER Andhika Rezky B. University of Trisakti
Dehydration is common condition that found in older adults. Older adults showed a general decline in total body water, and even this loss of body water was the cause of all symptoms of aging. Homeostasis of fluid balance is an important prerequisite for healthy aging. The high prevalence of disturbances of fluid balance among older adult patients has triggered us to make this photograph. Dehydration is the result of a fluid imbalance therefore an inadequate circulating volume resulting from either the consumption of too little fluid or due to a loss of too much fluid. Environmental and disease-related risk factors for dehydration have a very high prevalence among older adults. Being over 85 years old and female, having five or more chronic diseases, taking five or more kinds of medication, and being bedridden were significant risk factors in developing a moderate degree of dehydration. Dehydration often causes atypical symptoms such as confusion, constipation, or less frequently fever or falls. Confusion, constipation, and falls are part of the very frequently occurring "geriatric giants." Maintaining the delicate fluid and electrolyte equilibrium of older adults (>65 years of age) is an integral part of nursing care. Caregivers play a crucial role in the prevention of dehydration, as it has been shown that verbal prompting to drink between meals was effective in improving fluid intake . It has been demonstrated that when older adults know that they should not trust thirst but should drink because it is healthy for them. Caregiver should allowing adequate time and supervision during meals, encouraging family members to participate in feeding, and registering fluid intake. This picture show you about the importance of caregiver role in preventing dehydration by providing mineral water every day and make sure that they drink well.
WILLING FOR BETTER LIVING Gerry University of Sebelas Maret
As we know, there’re countless diseases that are ready to attack the elders. Age, as the main factor, affect the body, causing problems such as decreased normal functions, regressive developments, and metabolic problems. We also notice that the symptoms and sickness of old people are correlated
with their life style and habits which accumulate as they’re aging.
Hundreds of infections await every moment because of reduced immune system. Women somehow are less fortunate because of menopause that contributes for more disease caused by hormonal imbalance.
In this piece of photograph, it’s shown that an elder women with walking stick of hers and that is helped by her daughter is walking towards social service that provided by AMSAIndonesia in NAE 2014, we can see her spirit to receive medical check-up and consult her health issues with doctors. It would be very helpful if all elders especially in Indonesia (as one of developing countries) have the eagerness to approach health facility, because without their own or their family awareness, it is difficult for health providers to follow-up their health condition.
It’s known now that geriatric problems couldn’t be solved if we only depend on the elders themselves, because not every elders are like this one in the photograph, we as young generations, play a great role for the betterment of elders’ health.
ALONE IN DESPAIR Januardi Indra Jaya University of Brawijaya
This photo was taken to address one of the most common problems of elderly yet preventable, depression. Depression is one of problem faced by elderly that can lead to increase the risk of cardiac disease, slow progression of rehabilitation and loss of appetite, like what it shown in the picture, which can lead to malnutrition and decreased their quality of life. We see the problem of depression in elderly are mainly because they feel alone and no one take care of them. The purpose of this photo is to raise the awareness of society that depression may happened to every elderly and they have to identify it because it is danger, moreover it account for most cases of suicide among elderly. We should be care for them, making their life more cheerful, and help them ease their problem and not letting them alone in despair
THEY NEED YOUR SUPPORT Januardi Indra Jaya University of Brawijaya
This photo is about an elderly who do a rehabilitation of his joint problem in a drizzled day helped by his daughter who gives him protection from the rain with her umbrella. It shows to us how one support can help elderly to successes their rehabilitation process and make them stick to schedule for rehabilitation even under rainy situation. Contribution of younger people in the current situation where the number of elderly is high is really important in order to maintain the quality of life and to prevent such a disability occur in elderly. Thatâ&#x20AC;&#x2122;s why we promote this image in order to spread the message to society that they need our support more than any other thing because without support from us, whatever things doctor plans to them whether itâ&#x20AC;&#x2122;s treatment or rehabilitation will never be successful. Yes, they really need your support!
CARING ELDERY Andreas Jeffrey University of Brawijaya
This photo tell us how we care to elderly.Elderly process of gradual disappearance - the land's ability to improve / replace themselves and maintain a formal function so it can not withstand the infection and repair the damage suffered. According to the organization's (WHO) includes the elderly middle age is the age group 45-59 years, Old age is the age group 60-74 years, Old age is the age group of 75-90 years old, and very old age is the age group above 90 years. Alzheimer’s desease is named by Dr.Alois Alzheimer in 1906.Alzheimer’s desease is a desease of the brain that causes problems with memory,thinking and behavior.it’s not normal part of aging.in most people with alzheimer’s symptoms first appear after age 60.Alzheimer’s desease is the most common cause of dementia among older people.dementia is the loss of cognitive functioning-thinking,remembering, and reasoning and behavioral abilities, to such an exent that it interferes with a person ‘s daily life and activities. Possible causes of memory problems include: •
Depression
•
Medication side effects
•
Excess alcohol use
•
Thyroid problems
•
Poor diet
•
Vitamin deficiencies
•
Certain infections
•
Alzheimer’s disease and related dementias How to treat Alzheimer’s desease
•
Maintaining Mental Function
•
Managing Behavioral Symptoms
•
Identifying the symptom
•
Understanding its cause
•
Changing the caregiving environment to remove
•
challenges or obstacles
PAIN OF LONELINESS Camoya Gersom University of Brawijaya
It is true that it is inevitable, the fact that children will someday leave their parents to take care of their own lives. It is actually a good thing to do, being responsible for your life, knowing how to feed yourself and your own family, knowing how to work hard to live. But it is also a fact that there are many elders that were not only left by their children, but they are also neglected, or maybe worse, forgotten. Elders need our care because most of them are no longer fit to work as hard as how they used to. It is saddening to know that many elders feel pain and fall into various diseases, not because they have bad immunity and nutrition, but because they feel lonely and stressed due to family members who left them. This picture is about a man who feels sad because many of his family have deceased and his children have left him to go after better lives. It is good to live a good life, but for whatever it's worth, never forget that your elders are in your care to enjoy a good life as well. After all they have done to us, how can we possibly just neglect them?
THE FRAIL STEP Chrisandi Yusuf University of Brawijaya
Do you remember how our parents were the ones who taught us how to walk? They would accompany us step by step, slowly but surely, making sure we learnt how to walk while at the same time protecting us from falling. Like any other humans, everybody will someday go back to how they were before. Learning how to walk. We will go back to the times where it was difficult to land a foot for a simple step. But before we're there, our predecessors are the ones who get there first. Don't you think it is our responsibility to pay them back by helping them? What man would want to stay at only one place just because their feet are getting more vulnerable and frail? It would be stressful, imagine if it happens to your parents and loved ones. Be the guide for a better quality of life. Start from the simplest things. Be the help to guide the frail steps. For it is not a life without living it with care. It is time for us the young generation, to reach their hands and to help and raise their life.
DO NOT ASK ME TO REMEMBER, JUST REMEMBER THAT “I NEED YOU” Amy Tryabto Arifin University of Hassanudin
This photograph captures an elderly person that has alzheimer’s disease which is a progressive brain disorder of the elderly. This disease is able to make someone gradually lose their memory bit by bit, starting with the smallest things like forgetting where you put things, forgetting some family members and relatives, forgetting ways to do some basic activities, and on a more extreme level, can be able to even not recognize his/herself one day. On this stage, the patient really needs presence of someone else to help do some daily activities and also to act as the patient’s memory in case the patient forgets something because an alzheimer’s patient can go to a depressive state when he/she fails to recall a memory that they find important to them. But it’s unfortunate that until this day, a precise cure is not found yet. Which makes the best that we can do to help the society now is to prevent this disease to grow even more severe by showing that we do care these patients and always give our love, and show patience in guiding the patient.
SMILE FOR LOVE Dilanny Puspita Sari Maranatha Christian Unviersity
The background of the photograph I took is Dementia which is a decline or loss of reasoning, memory, and other mental abilities (the cognitive functions such as judgment, thinking, behavior, and language), mostly caused by advancing age. Now considered to be normal in elderly. But of course could be avoided, and if its already happen we can still enhance the quallity of life of the patients. Its my grandmother in the picture, she has Dementia, in her late 70s age. She was a teacher, a baker, a leader in some organizations she used to active in, and i tell you sheâ&#x20AC;&#x2122;s really an active lady, even after she retired. To see her right now like 180! from what she used to be. Sometimes really shocked me, how a really independent woman who takes care of whether it herself or anybody else, can be that brittle, dependent, and confused. This is my grandmother after she got bathed by my mom (who really avoided the camera). My mom takes care of my grandma really really well, really patient, and with all her heart. She know the disease is irreversible, and of course will get even worse, but she always maintain my grandmaâ&#x20AC;&#x2122;s quality of life. She bathes her, feeds her, then in the night she accompany her. So this is the point I wanna deliver. We may cant reverse the disease. But in the picture, my grandma smiles, because I know deep there she feels loved. And thats what important, to enhance her quality of life, to make her feels loved, that she still have a family she can counts on. Thats what gonna make her stay around for little more while, to stabilize her condition for more time.