TopDoctors 18 by Top Doctors

issue 18

:: Your Guide To Living Well ::

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Top Doctors Magazine

Brain-stimulating activities reduce risk of cognitive impairment in seniors

“Brave the Shave for Kids with Cancer” 2017

Dr Dona Cooper MD

March is Colon Cancer Awareness month. On this edition of Top Doctors Magazine, I have invited Dr. Subrahmanyam Behara of Renaissance Gastroenterology to educate us about the important role colonoscopies play in early detection of colon cancer. Getting screened can save your life! I would also like to congratulate Dr. Dona Cooper on the release of her new book “Get Healthy for Life.” It talks about how to live a longer, stronger and more energetic life. And last, as a member of the Valley Alliance of Mentors for Opportunities (VAMOS), I would like to thank the staff, board members, committees and sponsors for their support and excellent work at our 2017 golf tournament. It was a success! We were able to raise funds for the scholarships that will be given to our local students. Once again, thank you and I hope you enjoy this edition.

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During this interview, when asked what inspired her to write the book, “Get Healthy for Life” Dr. Cooper replied, “As I began to reassess my purpose in life and ponder on my effectiveness as a physician in making lasting changes in the lives of my patients, I also began to ask myself, “Why are so many people dying from diseases such as diabetes, hypertension, heart disease and cancer? How do we stop the epidemic of obesity and diabetes in our children?” She was concerned that if this trend continued, the children’s lifespan will be shorter than that of the parents.

HAVEN 27 SAFE FORENSIC EXAM CENTER Dr. Cooper explained, “It is very obvious that we are living in an era of advanced medical science and in the United States of America we have the best hospitals, well trained healthcare providers, and the most advanced technology, yet patients are sicker than they have ever been and thousands are dying daily from diseases that are not only preventable, but also curable.”

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Colon Cancer The Importance of

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Screening

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Even though I promised to give you the perfect diet to start off the newyear, everyone has to look for their own diet. Your mom is right, you are unique. Meanwhile lets help you with one that could lead you to possibly your perfect diet. That might be the Ketogenic diet, another typical fad diet? Actually, it’s been around for a while now and people get some pretty good results from it. So what exactly is so different? Well most of these fad diets simply tell you to eat certain types of food and avoid those certain types of food and «voila» you’re on your way to losing 100 pounds, not really. What’s special about the Ketogenic diet is that it changes how your body feels and most importantly how your body uses energy by placing you in a state known as Ketosis, and this is where all the magic happens. In Ketosis your body starts utilizing substances known as Ketone bodies which are produced by the breakdown of your body fat. It is important for you to first understand that your body loves glucose, and if it has glucose on hand it’s going to use that first for energy. In a Keto diet the amount of carbohydrates you consume goes down, therefore in order to combat the fat your body uses stored glucose but that eventually is going to run out as well. The next step your body will do is to convert Ketones into energy with a few steps that happen with the liver and the Kreb cycle ( series of chemical reactions to release energy from carbohydrates, fats, and protein). This also is really good news for your brain since your brain loves glucose, it can function on Ketone bodies as well. In fact, Ketone bodies provide more energy per gram for the brain v.s. glucose. So it’s a win- win for your mental capacity. Now, so far everything sounds good , your body doesn’t rely so heavily onto carbohydrates, burns a lot of fat and your brain functions pretty well, but of course there is always

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Top Doctors Magazine

a catch. A number of catches in this case study shows that power output decreases in cases where maximum intensity is required. This makes sense because the breakdown of glucose via Glycolysis (breakdown of sugar into energy) is a crucial role in providing the immediate energy for your body. When there is no glucose and glycogen in your body, intense workouts become a lot harder and the lack of glycogen also affects muscle growth since there is a strong positive connection between glycogen availability and protein synthesis take the glycogen away and the process slows down. Also, there is the Keto flu; something that happens when your body starts transitioning off the carbs and rely more heavily on ketone bodies. The Keto-flu which isn’t an actual flu contains symptoms such as headache, fatigue, coughing, nausea, upset stomach. The positive note though is that passes quite quickly and won’t come back again unless you get out of Ketosis (approximately five days into Keto diet). The Keto diet is also very food restricted. A conventional diet has you eating about 50% carbohydrates, 20% fat, and 30% protein and a Keto diet on the other hand has you eating up to 70% fat, 25% protein, and 5% carbohydrates or at least under 30 grams.

That is a huge change most people cannot do. Cutting out so many carbohydrates is easier said than done. This is a huge bout by it self and a lot of times a losing battle but even with the drawbacks people still advocate for it (as I do for some of my trainees). The reason that is the case can be summed up from this study in the Ann Internal Medicine of 2004, a low carbohydrate diet such as a Keto diet had better participant retention compared to a low fat diet. That is saying even though with all the drawbacks, individuals on a Keto diet find much easier to stick to the diet more so than a conventional one. This is because with so much more fat and protein dense foods your satiety or fullness level goes up much faster. A 200 Calorie chicken breast or 200 calories worth of green leafy vegetables will make you feel more full then say 200 calorie carb-heavy pasta. Even if that is the case, a calorie is still a calorie. Yes, protein and fat calories will make you feel more full but won’t help you lose weight if you’re eating more calories than you can burn .

·To start you off eat proteins that are low in fats example: chicken breast, turkey breast, white fish, tuna ·You can mix in some of the ones that have more fat for example: sirloin, salmon, trout, eggs ·Add a lot leafy vegetables but stay away from some examples: breads, tortillas, potatoes, fruits, dairies, starches, sugars Is the Keto Diet for you? Well, it all comes down to it «DEPENDS». If you’re a person that struggles with feeling full when going on a weight loss diet then «yes», then the Keto diet might help you fight those feeding frenzies, just remember those drawbacks that will occur. At the end of the day it still comes down to calories in versus calories out. On the next article we will be talking about where the fat goes when you «burn it off .» Who can guide me for a Ketosis diet? There is a lot of books on the subject matter but only a handful people know how to guide people going through this type of diet. If you need more information you can contact me via social media my contact information is down below. Happy new year, god bless, and let’s keep encouraging each other.

Follow me on: @theycallmeyoda Albert Gramoff

Brain-stimulating activities reduce risk of cognitive impairment in seniors According to several long-term studies, mild cognitive impairment (MCI) affects between 16 and 20 percent of people aged 65 and over. MCI refers to a loss of cognitive function that is not severe enough to interfere with daily activities, but which is very likely to develop into dementia. Numerous studies suggest that between 20 and 40 percent of people who have MCI go on to develop dementia. New research examined the link between brain-stimulating activities and cognitive functioning in healthy adults aged 70 and over. The researchers also assessed the influence of the apolipoprotein E (APOE) ε4 genotype. Studying the link between MCI and brainstimulating activities

The team examined 1,929 cognitively healthy seniors in Olmsted County, MN. The participants were examined and deemed normal at the beginning of the study. They provided information about their participation in brain stimulating activities during the year preceding their enrolment in the study. Researchers then clinically followed the participants for approximately 4 years to see how many of them developed MCI. They performed neurocognitive assessments of the seniors at baseline and evaluated them every 15 months. In their statistical analysis, Dr. Geda and team used Cox regression models

and adjusted for sex, age, and education. The team also took blood tests from the participants to determine APOE ε4 genotyping. The APOE ε4 genotype is a variant in the APOE gene commonly associated with a high risk of late-onset dementia. Existing research has not yet uncovered the mechanism responsible for this association, but it has found links between the gene variant and the buildup of Alzheimer’s-related amyloid plaques. Brain-stimulating activities lower the risk of MCI

The researchers found that brainstimulating activities significantly decreased the risk of new-onset MCI. Some of these activities included computer use, crafts, social activities, and playing games. The association between reading books and a decreased risk of MCI almost reached statistical significance. According to the authors, the findings mean that engaging in brain-stimulating activities even in later life can lower the chances of developing MCI. Researchers also noted the lowest risk of MCI in those participants who engaged in mentally stimulating activities, but who were not APOE ε4 carriers. Conversely, they found participants who did not engage in cognitively stimulating activities, and who were also carriers of APOE ε4, to have the highest risk of MCI.

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“Brave the Shave for Kids with Cancer” 2017

St. Baldrick’s Foundation and Doctors Hospital at Renaissance Health System hosted the 9th Annual RGV “Brave the Shave for Kids with Cancer” event on Sunday, February 26, 2017. In an effort to raise funds for childhood cancer research, members of the community, and members from TeamDHR, shaved their heads in solidarity with the many children braving the fight!

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E-CI GA RET TES

MAY INCREASE CARDIOVASCULAR RISK Electronic cigarettes are becoming increasingly popular, but little is known about the risks they pose to cardiovascular health. New research investigates the link between habitual electronic cigarette use and cardiovascular risk.

More and more people use electronic cigarettes (e-cigarettes) instead of conventional ones, as the former are perceived to be safer. E-cigarettes do not contain tobacco and do not involve combustion. However, e-cigarettes still contain the addictive nicotine and some of the chemicals found in regular cigarettes. In 2009, the U.S. Food and Drug Administration (FDA) warned that e-cigarettes contain “detectable levels of known carcinogens and toxic chemicals to which users could be exposed.” New research examines the link between regular e-cigarette use and the implications for cardiovascular risk. Analyzing cardiovascular risk factors in those who use e-cigarettes The study was led by Dr. Holly R. Middlekauff, of the David Geffen School of Medicine at the University of California in Los Angeles, and the findings were published in the journal JAMA Cardiology. Dr. Middlekauff and team hypothesized that people who routinely use e-cigarettes would have increased oxidative stress and an imbalance in the cardiac autonomic tone - both considered cardiovascular risk factors.

They say: “Nicotine, which is the major bioactive ingredient in e-cigarette aerosol, with its metabolites, may harbor unrecognized, sustained adverse physiologic effects that lead to an increased cardiovascular risk profile in habitual e-cigarette users.”

The team gathered 23 healthy users of e-cigarettes aged between 21 and 45 who did not smoke conventional cigarettes and were not taking any prescription medication. The study also used a control group consisting of 19 healthy individuals that met the same criteria but were not users of e-cigarettes. Researchers performed an electrocardiogram to measure the participants’ heart rate variability during both quiet rest and controlled breathing. They distinguished three different spectral components - high frequency, low

frequency, and very low frequency. The team also took blood tests and analyzed the blood for parameters of oxidative stress. Finally, Dr. Middlekauff and colleagues conducted a statistical analysis. E-cigarette users are more likely to have cardiovascular risk factors. The findings confirmed the researchers’ hypothesis. The low-frequency component, as well as the low frequency to high frequency ratio, were increased among the e-cigarette users. This suggests that people who used e-cigarettes experienced a shift in their cardiac autonomic balance towards sympathetic predominance. The sympathetic nervous system takes control of the cardiovascular system in “emergency” situations. It produces the “fight or flight” response when the individual is in danger, increasing the adrenaline levels in the heart. As for oxidative stress markers, the researchers found an increased level of low-density lipoprotein oxidizability. This indicates that lipoproteins containing the apolipoprotein B are prone to oxidation. Overall, this means that compared with the control group, users of e-cigarettes were more prone to increased cardiac sympathetic activity and increased oxidative stress - both signs of tobacco-related cardiovascular risk. Therefore, habitual e-cigarette use has physiologic effects, many of which may seriously affect the users’ cardiovascular health. The authors caution against the cardiac risks and recommend further investigation of the adverse health effects of inhalable nicotine.

In an exclusive interview, Top Doctors magazine had the privilege and honor to interview Dr. Cooper, who is no ordinary doctor. She is described as a “Doctor on the Move,” positively changing healthcare outcomes in the Rio Grande Valley. In her latest book, “Get Healthy for Life,” she invites readers to “Discover the 9 Secret Pillars of Health to Live a Longer, Stronger, More Energetic Life.” During this interview, when asked what inspired her to write the book, “Get Healthy for Life” Dr. Cooper replied, “As I began to reassess my purpose in life and ponder on my effectiveness as a physician in making lasting changes in the lives of my patients, I also began to ask myself, “Why are so many people dying from diseases such as diabetes, hypertension, heart disease and cancer? How do we stop the epidemic of obesity and diabetes in our children?” She was concerned that if this trend continued, the children’s lifespan will be shorter than that of the parents. Dr. Cooper explained, “It is very obvious that we are living in an era of advanced medical science and in the United States of America we have the best hospitals, well trained healthcare providers, and the most advanced technology, yet patients are sicker than they have ever been and thousands are dying daily from diseases that are not only preventable, but also curable.”

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Top Doctors Magazine

Dr. Cooper has experienced more than twenty-five years of love, dedication, long hours at the office, stressful hospital rounds, home visits, but yet felt the love and passion which she once had for medicine was slowly vanishing.

Clinic,Walk with the Dr., Dinner with the Doctors, community programs such as the “Pharrmacy Program” in conjunction with the Food Bank located in Pharr, Texas, in which vegetables are donated to her patients.

As a result, Dr. Cooper became inspired and engaged in helping people live a healthier life and wanted to create awareness. And this is where she began her journey to give the gift of health. In this special issue we are excited to announce the most recent gift of health from Dr. Cooper- the release of her very own first book Get Healthy for Life which is now a Best Seller book! And the excitement does not stop there, she is the author of several other books which will be out soon! We might me able to give you a sneak peek of her upcoming book #2… stay tuned! Follow her on www.gethealthywithdrcooper.com

She also just opened the Cooper Wellness Health Food Store where wellness solutions will be offered with a full line of vitamins, supplements, shakes and much more!

Dr. Cooper gives the gift of health thorough many philanthropic activities in which she actively participates. In 2010 she founded Faithful Path Ministries, a non-profit organization, to provide free health to marginal (underprivileged) communities world wide. “My next international medical humanitarian event will be June 29- July 9, 2017, I will be providing medical aid in the country of Senegal, West Africa” she explained. For more details visit email: donadockerymd@gmail.com The AMEN Clinics (Adventist Medical Evangelistic Network) is another organization where she travels as a volunteer around the world donating her time while helping the underprivileged and uninsured so that they are able to receive free medical aid. In 2016, with hard work and dedication Dr. Cooper started efforts to bring the AMEN Clinic to our area. The dream became a reality a Mega Clinic -which normally occurs in places like Los Angeles, San Antonio, Greece, Haiti, etc.- now was taking place right here in the heart of the RGV, it was named “Get Healthy Mega Clinic.” The mega clinic- which now became a yearly event- was not only a total success, but a blessing to many. With the help and support of wonderful volunteers, healthcare providers, sponsors, among others over 1,400 patients received aid, more than two million dollars in services were rendered, more than 540 volunteers participated, and over 60 healthcare professionals donated their time. Additionally, Dr. Cooper also gives the gift of health while she shares her messages of hope and healing in her television show “Get Healthy with Dr. Cooper,” in her magazine called Get Healthy during her many events such as Get Healthy Mega

Dr. Cooper shared that during her twenty-five years and over of practicing internal medicine she had seen too many lives destroyed as a result of diseases which are easily preventable with the integration of simple lifestyle changes. She said “Therefore, for the past several years I have integrated the GET HEALTHY FOR LIFE solution to empower my patients to change their health destiny. In this program the emphasis is placed on educating, inspiring and empowering the patients to change lifestyle habits. This program addresses the root causes of diseases. Patients are instructed on how to make simple, but effective changes that will not only lead to prevention, but in many cases to patients experiencing disease reversal.” Dr. Cooper said, “I can now truly say that my love for medicine has never been stronger.” She now spends more time working with her patients, educating them on how to live their lives differently in order to prevent or reverse chronic diseases. Her patients are now enjoying better health, they are happier and they now have a new vision in life. We asked Dr. Cooper to share with us some insights about her new Best Seller book Get Healthy for Life and this is what she said “As you continue to read my book you will be educated on various important subjects such as the impact that food, exercise, rest, healthy relationships and faith has on health and longevity. As for me, I am delighted. I am excited because I am experiencing so many health miracles in the lives of my patients. I am a doctor on the move with the goal to positively change healthcare outcomes using lifestyle modifications, for all the people I am able to reach. Why don’t you join the movement! My goal is to educate, inspire and empower you too!” Order your very own copy of this Best Selling Book NOW simply go to: www.gethealthywithdrcooper.com For more information visit the Cooper Wellness Center 3604 N. McColl Rd. McAllen, TX 78501 or call 956-627-3106 or go online: www.cooperwellnesscenter.com / Cooper Internal Medicine located at 801 E. Nolana Ste. 12 McAllen, TX or call 956-686-8802. www.cooperinternalmedicine.com

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DEMENTIA BY AIR POLLUTION A FIFTH OF DEMENTIA CASES MAY BE CAUSED BY AIR POLLUTION, STUDY SUGGESTS New research strengthens the previously reported link between air pollution and cognitive decline, after finding that exposure to fine particulate matter could significantly raise the risk of developing Alzheimer’s disease and other dementias.

the EPA’s permissible limit in 2012 (35 micrograms per cubic meter of air) - were found to be at an 81 percent greater risk of global cognitive decline and have a 92 percent increased risk of developing Alzheimer’s disease and other dementias.

The research found that exposure to high levels of particulate matter 2.5 (PM2.5) - tiny air pollution particles that are up to 2.5 micrometers in diameter - increased older women’s risk of dementia by over 90 percent, compared with low PM2.5 exposure.

The results remained after accounting for numerous confounding factors, including race and ethnicity, socioeconomic status, lifestyle, and the presence of other medical conditions. The researchers estimated that if their findings ring true among the general population, then exposure to high PM2.5 levels could contribute to approximately 21 percent of dementia cases.

Senior study author Prof. Caleb Finch, of the Leonard Davis School of Gerontology at the University of Southern California (USC), and colleagues say that if their findings apply to the general population, then PM2.5 could account for around a fifth of dementia cases. The researchers recently reported their findings in the journal Translational Psychiatry. - PM2.5 are fine particles consisting of solids and liquid droplets that are emitted from sources involving combustion, such as power plants and motor vehicles. - PM2.5 are 2.5 micrometers in diameter or smaller. To put their size into perspective, the diameter of a PM2.5 particle is around 30 times smaller than that of a human hair. Because they are so small, PM2.5 are easily inhaled, which can pose numerous problems for health. According to the United States Environmental Protection Agency (EPA), exposure to fine air particles can increase the risk of heart attacks, asthma, and reduced lung function, as well as premature death for individuals with heart or lung disease. In recent years, studies have suggested that exposure to such pollution may also raise the risk of dementia. Prof. Finch and team decided to investigate this association further in their new study. Alzheimer’s risk increased by 92 percent with high PM2.5 exposure. The researchers arrived at their findings by analyzing the data of 3,647 women from 48 U.S. states who were part of the Women’s Health Initiative Memory Study (WHIMS). All women were aged between 65 and 79 and were free of dementia upon study enrollment. As part of the WHIMS, participants’ cognitive function was assessed annually. Using data from the EPA, the team estimated the women’s daily PM2.5 exposure at their place of residence. Compared with women who lived in areas exposed to low PM2.5 levels, those who resided in areas with high PM2.5 levels - defined as levels that exceeded

Air pollution may worsen plaque formation in presence of APOE ε 4 gene. Interestingly, the increased risks of global cognitive decline and dementia as a result of high PM2.5 exposure were strongest among women who possessed the APOE ε4 gene, which is associated with the development of Alzheimer’s. With this in mind, the team conducted mouse experiments in order to investigate how PM2.5 exposure affects the brain in the presence of APOE ε4. Using cutting-edge particle concentrators, the researchers exposed two groups of female mice to nano-sized air pollution for 15 weeks. One group possessed the APOE ε4 gene and one did not. Study co-author Constantinos Sioutas, of the USC Viterbi School of Engineering, explains that the particle concentrators “essentially take the air of a typical urban area and convert it to the air of a freeway or a heavily polluted city like Beijing.” “We then use these samples to test exposure and assess adverse neurodevelopmental or neurodegenerative health effects,” he adds. Compared with mice without the APOE ε4 gene, those that possessed the gene were found to accumulate around 60 percent more beta-amyloid plaque in their brains. Plaques are clusters of beta-amyloid protein, which are believed to destroy neurons. According to the researchers, their findings provide “clear evidence” that fine particle air pollution is related to dementia risk, and they provide the first evidence that exposure to these particles can exacerbate beta-amyloid accumulation. The team plans to conduct further studies that will assess how high PM2.5 exposure influences cognitive function in both men and women.

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HEALT SYSTEM DHR had our Quarterly Night Owl visits!!! Our amazing leadership team came together to go around and recognize our awesome night shift employees. Thank you to all our employees for all that you do!

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FORENSIC EXAM CENTER AT RENAISSANCE On Friday, February 3, 2017, Doctors Hospital at Renaissance Health System announced the opening of Safe H.A.V.E.N.â&#x20AC;&#x201D;Helping All Violent Encounters Now. Safe Haven is a forensic exam center that provides comprehensive, compassionate, and patient-focused care for children and adults that have been abused or sexually assaulted. Members of the medical community, local and federal officials and law enforcement attended the press conference to learn more about this much needed community service. Safe Haven services can be accessed through the DHR emergency department or by calling 956-362-5100.

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Subrahmanyam Behara, MD Gastroenterologist

Colon Cancer and

by: Subrahmanyam Behara, MD

Colorectal cancer is the third most common cancer and cause of death from cancer in the United States. However, it can be detected in asymptomatic patients at a curable stage – with an easy screening exam. Several studies have shown lower mortality among those patients who undergo a screening colonoscopy versus those who don’t. Screening detects polyps that can be removed during the colonoscopy, which in turn can prevent the polyps from leading to colon cancer. Colon cancer is a disease that afflicts both men and women, so everyone over the age of 50 should speak with their physician about being screened.

50 compared to Caucasians. Ashkenazi Jews also have higher incidences of colorectal cancer.

The Importance of Screening

Risk Factors: A key risk factor of colon cancer is age, with dramatic increases in colorectal cancer incidence after age 50. Another key factor is family history. Persons who have had a family member affected by colon cancer have an increased risk for developing the disease themselves. Patients with familial colorectal cancer typically present at a younger age than those with sporadic disease. Since most malignant polyps form slowly, over 10 years or so, it is recommended to have your first screening 10 years before the age at which a close relative was diagnosed. First degree relatives with colorectal cancer increases an individual’s lifetime risk two-fold. If an individual younger than the age of 45 develops colorectal cancer, the lifetime risk for first-degree relatives is about 20%. Individuals with certain recognized syndromes, such as Lynch syndrome and familial adenomatous polyposis, have an 80% and 100% lifetime risk, respectively, for developing colorectal cancer. The presence and duration of colitis in inflammatory bowel can also increase the risk of colorectal cancer. Ethnicity and race are risk factors as well. African Americans have a higher incidence and death rate of colorectal cancer and have a higher proportion of colorectal cancer under the age of

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Obesity, diabetes and smoking have been independently associated with an increased risk of colorectal cancer while physical activity has consistently been shown to protect against colorectal cancer. Environmental factors such as consumption of red meat, high fat intake, alcohol, tobacco usage, and menopause confer some risk. Diets higher in fish, calcium, dairy, fruit, vegetables and selenium are associated with a lower risk. Screening, surveillance and prevention Adenoma’s (polyps) and early cancers are often asymptomatic but potentially curable if found and removed, while symptomatic colorectal cancer is more likely to be in advanced stage. Screening men and women at age 50 or above for colorectal cancer has shown to increase survival. Screening colonoscopy reduces cancers by 68 to 80% in persons who undergo the exam. Average screening should start at the age of 50. Several organizations recommend the screening for patients between 76 to 80 years of age should be tailored on the basis of presence of coexisting illnesses and screening should be stopped after 85 years of age. My recommendations: 1. Start screening colonoscopy at age 50 and every 10 years thereafter. 2. If adenomatous polyps are detected, have a repeat colonoscopy in 3 to 5 years depending on the number and size. 3. If there is a family history, start screening colonoscopy at age 45 or 10 years earlier than the age at which the relative developed cancer. 4. Avoid red meat, processed meat, a high fat diet, alcohol and tobacco. 5. Exercise regularly. Have a diet high in fish, vegetables, dairy and fruit. Take selenium, calcium and vitamin D.

Low levels of glucose in the brain may trigger Alzheimer’s More than 5 million people in the United States live with Alzheimer’s disease. Before they develop the full-blown illness, many of these patients start experiencing a mild form of cognitive impairment. This can include problems with their reasoning, judgment, or memory that are greater than normal, yet do not interfere with daily functioning. As recent studies have suggested, even before the first signs of cognitive impairment, the levels of glucose in the brain begin to decline. Glucose is crucial for good cognitive functioning. In fact, our brains rely heavily on this source of energy, using half of all the sugar in our body to fuel reasoning, memory, and learning. New research - led by Dr. Domenico Praticò, a professor at the Center for Translational Medicine at the Lewis Katz School of Medicine at Temple University in Philadelphia, PA investigates more deeply the impact that glucose deprivation has on the brain. The findings were published in the Nature journal Translational Psychiatry. Studying the impact of glucose deprivation on the brain. Dr. Praticò has shown in a previous study that, to make up for glucose deprivation, the brain builds up the protein called phosphorylated tau. The tau protein then creates so-called tangles - “gridlocks” of twisted fibers of tau that block the transportation of nutrients through to the neurons. Eventually, these tangles cause the brain cells to die. A larger number of tau tangles is usually associated with an increased severity of Alzheimer’s and dementia. The previous study by Dr. Praticò investigated this mechanism in vitro and showed that tau buildup occurs using the P38 kinase pathway. In this new research, the team has examined the mechanism of tau phosphorylation as a response to glucose deprivation in vivo, using a mouse model.

Dr. Praticò and colleagues used mice that have been genetically modified in a way that replicates memory problems and tau pathology typical of Alzheimer’s disease. When the mice were 4 or 5 months old, some of them were administered 2-deoxyglucose (DG) - a chemical compound that prevents glucose from entering the cell and being processed into energy. The mice were injected with the substance over several months, and at the end they were tested for cognitive function using maze tests to evaluate memory and learning. P38 kinase directly associated with memory impairment. The glucose-deprived mice performed much worse in the cognition tests than those that had not received DG. Additionally, a microscopic evaluation of the mice’s brains revealed that neurons in the glucosedeprived mice had abnormal synaptic functioning. Memory encoding and storage were impaired because the interneural synapses were unable to communicate properly with each other. Furthermore, the researchers also found high levels of phosphorylated tau and high numbers of dead cells in the brains of DG-treated mice. Following up on Dr. Praticò’s previous research, the team examined P38 activation and found it to be directly associated with memory deficits. “The findings are very exciting,” says Dr. Praticò. “There is now a lot of evidence to suggest that P38 is involved in the development of Alzheimer’s disease.” According to him, the findings support the fact that even small episodes of chronic glucose deprivation can damage the brain. “There is a high likelihood that those types of episodes are related to diabetes, which is a condition in which glucose cannot enter the cell. Insulin resistance in type 2 diabetes is a known risk factor for dementia,” Dr. Praticò explains. The authors conclude by noting that this is the first time that a study has offered “in vivo experimental evidence” that glucose deprivation in the brain - by activation of the P38 kinase pathway - triggers memory and cognitive impairment, synaptic miscommunication between neurons, and neuronal death. They also comment on the possibilities for treatment, as this is the first time that P38 has been identified as a potential new drug target for Alzheimer’s disease: “Drugs targeting this kinase in the brain may represent a suitable therapeutic approach for the treatment of both AD [Alzheimer’s disease] and related tauopathies for which impaired glucose utilization is an established risk factor.”

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