Professor of Clinical Neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Director, The Danish Dementia Research Centre, Copenhagen, Denmark
and
Alistair Burns
Professor of Old-Age Psychiatry, University of Manchester, Manchester, UK; Consultant Old Age Psychiatrist, Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
3
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Acknowledgements
Thank you to Kate Freeman for her invaluable administrative support during the editing of Alzheimer’s Disease, second edition.
3 The planning of appropriate medical and social care in dementia 111
Marcel G.M. Olde Rikkert, Irena Draskovic, and Myrra Vernooij-Dassen
4 Case vignettes 117
Valeria Manera, Elsa Leone, Jennifer Thompson, Roland Zahn, Alistair Burns, and Gunhild Waldemar
Index 2
Contributors
Shelley J. Allen
Sigmund Gestetner Senior Research Fellow, Southmead Hospital, Bristol, UK
Hélène Amieva
Professor of Psychogerontology, University of Bordeaux, Bordeaux, France
Rafael Blesa
Director, Hospital de la Sant Pau, Barcelona, Spain
Henry Brodaty
Director, University of New South Wales, Sydney, Australia
Alistair Burns
Professor of Old-Age Psychiatry, University of Manchester, Manchester, UK; Consultant Old Age Psychiatrist, Greater Manchester Mental Health NHS Foundation Trust, Manchester, UK
Krishna Chinthapalli
Clinical Research Fellow, UCL Institute of Neurology, London, UK
Irena Draskovic
Senior Researcher, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Anne A. Fetherston
Academic Clinical Fellow and Specialist Registrar in Old-Age Psychiatry, Newcastle University, Newcastle, UK
Laura Fratiglioni
Professor and Director, Karolinska Institutet, Stockholm, Sweden
Julian C. Hughes
Consultant in Psychiatry of Old Age and Honorary Professor of Philosophy of Ageing, Newcastle University, Newcastle, UK
Matthew Jones
Consultant Neurologist, Salford Royal Foundation NHS Trust, Salford, UK
Roy W. Jones
Director, RICE—The Research Institute for the Care of Older People, Royal United Hospital, Bath, UK; Honorary Professor, University of Bath, Bath, UK; Honorary Professor, University of Bristol, Bristol, UK
Elsa Leone
Neuropsychologist, Centre Hospitalo Universitaire, Institut Claude Pompidou, Nice, France
Alberto Lleó
Clinical Head, Hospital de la Sant Pau, Barcelona, Spain
Valeria Manera
Neuropsychologist, Institut Claude Pompidou, CoBTeK, University of Nice Sophia Antipolis, Nice, France
Marcel G.M. Olde Rikkert
Professor, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Chengxuan Qiu
Associate Professor, Karolinska Institutet, Stockholm, Sweden
Contributors x
David Renaud
Physician, Centre Hospitalo Universitaire, Institut Claude Pompidou, Nice, France
Louise Robinson
Professor of Primary Care and Ageing and Director, Institute for Ageing, Newcastle University, Newcastle, UK
Philippe Robert
Professor, Institut Claude Pompidou, CoBTeK, University of Nice Sophia Antipolis, Nice, France
Katrin Seeher
Research Associate, University of New South Wales, Sydney, Australia
Jennifer Thompson
Neuropsychologist, Salford Royal NHS Foundation Trust, Salford, UK
Myrra Vernooij-Dassen
Professor, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
Gunhild Waldemar
Professor of Clinical Neurology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Director, The Danish Dementia Research Centre, Copenhagen, Denmark
Roland Zahn
Senior Clinical Lecturer, King’s College London, London, UK
Abbreviations
ABAD Amyloid β-peptide binding protein alcohol dehydrogenase
ABC ATP-binding cassette
ACP Advance care planning
AD Alzheimer’s disease
ADAS-Cog Alzheimer’s disease Assessment Scale
ADI Alzheimer’s Disease International
ADRT Advance decision to refuse treatment
AICD APP intracellular domain
APh Anterior pharynx-defective phenotype
APOE Apolipoprotein
APP Amyloid precursor protein
AT Assistive technology
BACE β-site APP cleaving enzyme
BDNF Brain-derived neurotrophic factor
BPSD Behavioural and psychological symptoms of dementia
BRACE Bristol Research into Alzheimer’s Disease
CCT Cranial computed tomography
CDK Cyclin-dependent kinase
CDRSB Clinical Dementia Rating scale–sum of boxes
ChEI Cholinesterase inhibitor
CIBIC Clinicians Global Impression of Change
CR Complement component receptor
CREB cAMP-response element binding protein
CSF Cerebrospinal fluid
DAD Disability Assessment for Dementia
DAT Dopamine transporter scanning
DLB Dementia with Lewy bodies
DSM Diagnostic Statistical Manual of the American Psychiatric Association
EEG Electroencephalography
EFNS European Federation of the Neurological Societies
LRP Low-density lipoprotein receptor-related protein
LTD Long-term depression
LTP Long-term potentiation
LXR Liver X receptor
lyPPA Logopenic variant progressive aphasia
MCA Mental Capacity Act
MCI Mild cognitive impairment
MMSE Mini-Mental State Examination
MOA Monoamine
MOCA Montreal Cognitive Assessment
mPTP Mitochondrial permeability transition pore
MRCCFA Medical Research Council Study on Cognitive Function and Ageing
MRI Magnetic resonance imaging
NDMA N-methyl-D-aspartate
NFT Neurofibrillary tangles
NGF Nerve growth factor
NHS National Health Service
NIA–AA National Institute on Aging–Alzheimer’s Association
NICE National Institute for Health and Care Excellence
NO Nitric oxide
NPI Neuropsychiatric Inventory
NSAIDs Non-steroidal anti-inflammatory drugs
PCA Posterior cortical atrophy
PEG Percutaneous endoscopic gastrostomy
PEN Presenilin enhancer
PET Positron emission tomography
PHF Paired helical filaments
PiB Pittsburgh compound B
POA Power of Attorney
PPA Primary progressive aphasia
PPAR Peroxisome proliferator-activated receptor
RCT Randomized controlled trial
REM Rapid eye movement
ROS Reactive oxygen species
RXR Retinoid X receptor
RYR Ryanodine receptor
sCJD Sporadic Creutzfeldt–Jakob disease
SES Socioeconomic status
SIB Severe Impairment Battery
SORL Sortilin-related receptor
SPECT Single photon emission computed tomography
SSRI Selective serotonin re-uptake inhibitor
TACE Tumour necrosis factor-α converting enzyme
TNF Tumour necrosis factor
TREM Triggering receptor expressed on myeloid cells
VASCOG International Society of Vascular Behavioural and Cognitive Disorders
VLDL Very low-density lipoproteins
Brayne 2006; UK
Prince, et al. 2013; US
Chan, et al. 2013; China
Anstey, et al. 2010; Australia
Figure 3. Age-specific prevalence of dementia (per 00 population) across countries.
The CSHA Group 2000; Canada
Matthews & Brayne 2005; UK
Plassman, et al. 2011; USA
Figure 3.2 Age-specific incidence of dementia (per ,000 person years) across countries.
Figure 5. Representative examples of MRI and FDG-PET scans in patients with Alzheimer’s disease. Panel A shows left hippocampal atrophy and hypometabolism (red arrows) in a patient with a typical amnesic presentation of AD. Panel B shows left-sided temporoparietal hypometabolism (yellow arrows) in a patient with the language presentation of AD. Panel C shows bi-parietal and occipital atrophy on the MRI and bilateral posterior hypometabolism on the FDG-PET (green arrow) in a patient with posterior cortical atrophy.
(B)
(C)
Dementia disorders: an overview
Roland Zahn and Alistair Burns
Key points
• Dementia is a clinical syndrome which comprises three domains: cognitive impairments, behavioural symptoms, and impairments of activities of daily living
• Dementia may be caused by a wide range of brain disorders and systemic conditions. Alzheimer’s disease (AD) is the most frequent cause of dementia
• Clinical interview, neuropsychological assessments, brain imaging, routine blood tests, and neurological examination are the most important instruments for differentiating between the causes of dementia
. What is dementia?
Dementia is a clinical syndrome operationally defined as cognitive impairment in at least two domains interfering with activities of daily living (Diagnostic Statistical Manual of the American Psychiatric Association: DSMIIIR and DSMIV-TR). Dementias are called major neurocognitive disorders in DSM-5, where impairment in only one domain documented by concern of patient or informant and neuropsychological tests, as well as interference with independence in everyday activities, is required. Classically, dementias referred to global cognitive impairment and always included prominent memory impairment. With the improvement of treatment, management, and diagnostic procedures, dementia disorders are detected at earlier stages and therefore the symptoms can often be focal rather than global. Dementia syndromes can also start with other symptoms than memory, for example language problems.
Although dementia in elderly people has been recognized by clinicians since a long time, it was only at the turn of the twentieth century that different causes and forms of dementia became suspected. This was possible due to following up patients with dementia syndromes during the course of their illness until death and then microscopically investigating silver-stained slices of their brains post-mortem.
In 906, Alois Alzheimer described neurofibrillary tangles and senile plaques in the brain of patient Auguste D. who had suffered from a progressive dementia, which we now call Alzheimer’s disease (AD) in recognition of this discovery. Despite these early case reports, it was not until the end of the twentieth century that sensitive clinical criteria were formulated that predict a probable post-mortem neuropathological diagnosis of AD. The sensitivity of clinical criteria for probable AD is very good (sensitivity above 80% with a specificity of about 70%). This means that the clinical diagnosis of AD is correct in most patients but that we may still diagnose somebody with probable
AD when neuropathology would show a different cause. Conversely, there are some patients with atypical symptoms who exhibit AD-typical neuropathological changes post-mortem, however with an atypical regional distribution leading to atypical symptoms. This differential diagnostic challenge will become increasingly important in the future when costly disease-modifying treatments become available, especially in case these treatments have serious side-effects.
.2 How frequent is dementia?
The prevalence of dementia increases with age, doubling with every five-year increase. Between 65 and 69 years of age the prevalence of dementia is estimated at .3% in the United Kingdom, rising up to 32.5% in people older than 95 years. Estimates of frequency of subtypes of dementia should be interpreted with caution because the clinical information available in large epidemiological studies is often insufficient for accurate differential diagnosis. Frontotemporal dementia (FTD) may be as likely as AD in patients younger than 65 years, but most people with dementia are late-onset patients (around 98% of all dementia patients in the United Kingdom). At least 60% of dementias are caused by AD and the proportion is higher if cases with additional vascular changes are considered (i.e. ‘mixed dementia’).
.3 Different forms of dementia and their diagnosis
One of the most important diagnostic instruments is the interview with a caregiver of the patient. In this interview it is important to ask for the first and most prominent symptom, the ‘lead’ symptom of the disease which often dates from many years earlier. Further, it is crucial to ask about the course of the problem, whether it started slowly or suddenly and at what pace the progression was noted.
Time course and lead symptoms indicate which diseases one needs to consider and rule out. As a general rule, one should be alarmed when there is a sudden or subacute onset, i.e. if the dementia syndrome has developed within weeks from normal functioning. Particular diagnostic attention should also be paid to rapidly progressing dementia syndromes in which there is marked decline within three to six months after onset. In both subacute onset or rapid decline, one needs to initiate a more detailed diagnostic assessment. This includes usually an analysis of the cerebrospinal fluid (CSF) to determine cell count and 4-3-3 protein sensitive to Creutzfeldt–Jakob disease (CJD) and the exclusion of encephalopathies caused by autoimmune or inflammatory diseases. A magnetic resonance imaging (MRI) examination including axial and coronal T-, T2-, fluid-attenuated-inversion-recovery, and diffusion-weighted images is needed in these patients. Electroencephalography (EEG) usually shows general slowing in encephalopathy patients. In CJD there are often characteristic triphasic complexes.
In the clinical history and blood tests it is also important to look for signs of an occult cancer (e.g. increased blood sedimentation rate) which may in rare cases lead to autoimmune reactions with antibodies directed towards neural tissue, or could cause brain metastases which do not necessarily show up on a cranial computed tomography (CCT) without contrast. In those cases an MRI should be considered. When cognitive impairment is slowly progressive, the neurological exam is otherwise normal and routine diagnostic assessments do not contradict a neurodegenerative disorder, then the diagnosis of a probable cause of dementia is guided by lead symptoms and the neuropsychological test profile (for an overview see Figure .). In neurodegenerative dementias,
Lead symptoms of dementia syndromes
Neurological examination
Past medical history and history of presenting complaint (patient + caregiver) If rapidly progressive (3–6 months) or subacute (weeks) onset If sig. abnormal
Lead symptoms
Impairment of recent memory
Behavioural changes
Impairment of language or speech
Fluctuating confusional states or impairments of attention
Visuospatial impairments
Further investigations
MRI, EEG, CSF to excl. Creutzfeldt–Jakob, autoimmune, or in ammatory encephalopathies
Typical AD?
Behavioural variant FTD?
Progressive aphasias?
Lewy-body dementia?
Posterior cortical atrophy?
Figure . ‘Lead’ symptoms are the most prominent and first symptoms to appear in the course of a dementia syndrome. Lead symptoms differ because neurodegeneration starts in different regions of the brain before spreading to other parts. Often they need to be explored retrospectively. This overview considers progressive cognitive disorders in which neurological symptoms (e.g. rigor, akinesia, muscle fasciculations, gaze palsy, orthostatic dysregulation and bladder incontinence, hyperkinetic movements, abnormal pupillary responses) are not prominent. If such symptoms are present, other forms of dementia need to be considered which are not discussed here. A CCT without contrast is needed in all patients to exclude haematoma, larger tumours, and normal pressure hydrocephalus. The degree of large or small vessel disease needs to be assessed on CCT. Neuropsychological test examination is necessary to identify characteristic profiles of impairment for different forms of dementia and to get objective confirmation of clinical reports. Other causes of dementia syndromes need to be considered if the clinical history or routine laboratory points to complex-partial seizures, chronic alcoholism, autoimmune disorders, signs of occult cancer or renal or liver failure, electrolyte changes, thyroid dysfunction, vitamin B2 and folate deficiencies. ‘Lead’ symptoms point in the direction of possible syndrome diagnoses. A syndrome is a combination of clinical symptoms and/or criteria which is defined in order to correspond most closely to a specific disease (i.e. aetiology). Here, we give an overview of which syndrome diagnoses one needs to consider for slowly progressive cognitive disorders in which the neurological exam and CCT appears normal or only shows atrophy and minor vascular changes. In order to establish a clinical syndrome diagnosis, one needs to check consensus criteria for the particular diagnosis (see suggested readings). As discussed in the text, it is impossible to find a one-to-one correspondence between a clinical syndrome diagnosis and a neuropathologically defined disease, but there are probabilistic associations.
the non-contrast CCT can appear normal or may show atrophy or small-vessel disease affecting less than one-quarter of the white matter. Differential diagnostic specificity increases when looking at regional distribution of abnormalities on structural T-weighted MRI, diffusion tensor-weighted MRI, 8-fluoro-deoxy-glucose positron emission tomography (FDG-PET), amyloid-beta (Aβ) biomarkers in CSF or amyloid
PET. Quantitative analysis of images is more sensitive and specific but rarely practiced in clinical settings (e.g. see Figure .2). See Chapter 5 for a detailed overview of the diagnosis of AD.
.3.
Impairment of recent memory
The lead symptom of impairment of recent memory is characteristic of typical AD. Patients cannot remember important events, such as family gatherings, which happened weeks or days ago. Old memories, such as childhood events, are relatively spared in the beginning of the disease. Impairments of recent memory are associated with the degree of damage to the medial temporal lobe and posterior cingulate cortex which are affected early in the course of typical AD (see Figure .2).
.3.2
Behavioural changes
The lead symptom of behavioural changes with intact recent memory and visuospatial skills is characteristic for the behavioural variant of frontotemporal dementia. Patients often show socially inappropriate behaviour (e.g. touching strangers), obsessive–compulsive behaviours (e.g. hoarding, repetitive behaviours, clock watching), and changes in food preference (e.g. preference for sweet foods). Neuropathology often shows classic Pick bodies in these patients. In some patients, standard neuropsychological tests can be normal, but caution is needed when making a diagnosis without neuropsychological or neuroimaging confirmation.
.3.3
Impairment of language or speech
The lead symptom of language impairment with intact non-verbal memory and visuospatial skills is characteristic of fluent and non-fluent forms of progressive aphasia. The fluent form is called semantic dementia because patients do not only lose the ability
Typical neuroimaging ndings in AD Parieto-temporal
Posterior cingulate/precuneus
Figure .2 Brain regions typically involved in patients with mild to moderate stages of AD are depicted: medial temporal lobe, posterior cingulate/precuneus and parieto-temporal cortex.
Data from unpublished single case analysis using Statistical Parametric Mapping Software (<http://www.fil.ion. ucl.ac.uk/spm/>, group results and methods further described in Zahn, et al., Psych. Res.: Neuroimaging (2005), 40: 5–3).
Decreased glucose-metabolism (blue) in one typical AD patient compared with aged controls
Decreased grey-matter volume (blue) in one typical AD patient compared with aged controls
to understand the meaning of words but also of non-verbal material such as pictures. Both forms are classified as forms of frontotemporal lobar degeneration, often confirmed by neuropathology. However, non-fluent patients frequently turn out to have AD with atypical distribution on neuropathology. Patients with progressive aphasia usually show intact delayed recall of geometric figures (e.g. a circle) from memory which distinguishes them from patients with typical AD on neuropsychology.
.3.4 Fluctuating confusional states or impairments of attention
Fluctuating confusional states warrant exclusion of autoimmune, inflammatory, paraneoplastic (i.e. antibodies against neural tissue in patients with occult cancer) as well as toxic and metabolic causes. The picture can occur together with visual hallucinations and neuroleptic hypersensitivity or Parkinsonian features in Lewy-body dementia. Multiple strokes or small vessel disease within the basilar artery territory also need to be considered.
.3.5 Visuospatial impairments
Some patients show predominantly visuospatial and apraxic difficulties due to atrophy of the occipital or parietal lobes (posterior cortical atrophy). Most of these patients show AD-typical neuropathology with atypical distribution.
.3.6 Vascular dementia
The diagnosis of vascular dementia or ‘major vascular cognitive disorder’ according to the International Society of Vascular Behavioural and Cognitive Disorders (VASCOG) criteria can only be made based on neuroimaging showing either multiple large vessel disease-related strokes, an extensive single infarct or haemorrhage in critical areas (usually thalamus or basal ganglia), multiple lacunar infarcts or haemorrhages in these areas, or extensive and confluent white matter lesions (more than one-quarter of the total white matter had been previously suggested). Despite these criteria, we have seen patients with extensive haemorrhages to basal ganglia and thalamus on MRI scans who showed mild cognitive impairments but no major changes in functioning after recovering from the acute phase. Milder cerebrovascular changes often contribute to the cognitive decline in AD and the distinction between ‘mixed’ dementia versus pure AD is gradual. White matter hypodensities on CCT do not need to be vascular; they can also point to other white matter diseases and should be carefully evaluated in marked cases. CSF analysis may be needed for differential diagnosis against inflammatory causes of white matter diseases.
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Pathophysiology of Alzheimer’s disease
Shelley J. Allen
Key points
• The neuropathological diagnosis of Alzheimer’s disease (AD), requires the presence of amyloid plaques and neurofibrillary tangles, which comprise β-amyloid (Aβ) and tau protein fragments respectively. This diagnosis still relies on post-mortem examination for certainty, although this may change with improved imaging techniques and biomarkers
• Familial AD (FAD), a rare form of dementia with early onset, may result from mutations in one of three genes, APP, PSEN, or PSEN2, each of which is directly related to the increased production of Aβ
• The ‘amyloid hypothesis’ suggests that Aβ is the principal stimulus for AD and that the ensuing disease process results from its overproduction or reduced clearance. This is still considered valid although an earlier role of tau in dementia is currently being given more prominence
• Aβ initiates the pathological process; abnormal phosphorylation of tau may be obligatory in continuing and amplifying this degenerative process. This has important implications for therapeutic strategies
• The relatively selective vulnerability of the projection neurones of the serotonergic, noradrenergic, and cholinergic systems, and the cortical glutamatergic systems provide the rationale for current pharmacological treatment
• The most robust risk, after increased age, for sporadic AD is the presence of the APOE ε4 allele coding for the apolipoprotein E4 (APOE) protein polymorphism. The protein APOE is involved in Aβ clearance and neuronal repair, whereas APOE4 contributes to an unfavourable outcome through a number of pathways. This may prove a challenge with respect to therapeutic approaches
• Symptoms become manifest 5–20 years after the initiation of pathological processes. Even mild cognitive impairment may represent an expression of established disease
2. Alzheimer’s neuropathology
For a definitive diagnosis of AD, post-mortem microscopic histopathological examination of the brain must reveal the deposition of two types of protein aggregates: parenchymal deposits of amyloid (Aβ) extracellularly as ‘plaques’, and intraneuronal deposits
of tau protein fragments as neurofibrillary ‘tangles’ (NFT), over and above that which occurs with normal ageing. Tau deposition may also occur as straight or paired helical filaments (PHF) surrounding plaques, and as argyrophilic neuropil threads, which are predominantly neuronal dendrites containing tau deposits. Additionally, at least 80 per cent of cases have congophilic angiopathy, with cerebrovascular amyloid deposited in small blood vessel walls of the leptomeninges and cerebral and cerebellar cortex.
All three protein aggregates can be visualized using a fluorescent dye, such as Thioflavin S (Figure 2.), which binds to proteins which form β-pleated sheets. With disease progression there is an overall reduction in brain size, especially in the hippocampus and temporal lobe, where cortical gyri become thinner and sulci wider. Certain neurotransmitter-specific pathways are particularly vulnerable including the cortical glutamatergic system and also projections from subcortical nuclei such as the serotonergic dorsal raphe, noradrenergic locus coeruleus and the cholinergic basal nucleus. Resultant neurotransmitter deficits may cause symptoms such as depression, aggression, and memory dysfunction, providing the rationale for the symptomatic drugs currently administered. There may be extensive gliosis, including hypertrophic astrocytes which have increased expression of glial fibrillary acidic protein (GFAP) and neuritic plaques frequently contain GFAP-positive astrocytic fibres. Microglial cells are increased in the grey matter near neuritic plaques and NFT. These are enlarged and are activated with increased expression of MHC Class II antigens and complement receptors; they may also express the receptor for advanced glycation endproducts (RAGE) which readily binds Aβ and mediates its effects. In later stages there is likely to be extensive cell loss with subsequent enlargement of the lateral and third cerebral ventricles. However, motor, sensory, and primary visual areas are generally spared until the end stages of the disease.
Figure 2. Microscopic examination of AD neuropathology in temporal cortex. A section of temporal cortex stained with Thioflavin S, a fluorescent stain, showing clusters of amyloid plaques and neurofibrillary tangles and cerebrovascular amyloid at low magnification. Insert (top left) shows higher magnification of an amyloid plaque; the image at top right) shows high magnification of neurofibrillary tangles.
Neuro brillar y tangles
Amyloid plaques
Cerebrovascular amyloid
Dysfunctional axonal transport due to NFT formation will affect passage of a number of proteins including growth factors. For instance, nerve growth factor (NGF), which is synthesized in the cortex and hippocampus and retrogradely taken to the cholinergic basal nuclei, is known to have impaired transportation.
The importance of NFT as a correlate of dementia severity was reported in 99 by Braak and Braak who described a well-defined route of deposition of increasing density with progressive stages of dementia. Stages and 2 of NFT deposition are largely subclinical and this degree of NFT deposition is fairly common in the normal elderly. NFT are largely restricted to the transentorhinal, entorhinal, and CAI regions of the hippocampus. At stages 3 and 4, NFT accumulates in the hippocampus and limbic system, and at the final stages, 5 and 6, this spreads to the neocortex. NFT deposition is statistically more closely linked, than amyloid accumulation, with stages of dementia. One reason suggested for this may be because of the extracellular location of amyloid plaques and the ready availability of clearance enzymes including insulin-degrading enzyme (IDE) and neutral endopeptidase (neprilysin) to remove the plaques. Removal of intracellular NFT may be thought of as more difficult and may result in the extended presence of a trail of neuronal ‘tombstones’. Amyloid plaques are frequently observed at the terminals of neurons which have intracellular NFT which suggests that tangles may form due to retrograde effects of Aβ actions at the synapse.
We now understand that the disease process is initiated at least 5–20 years before the first symptoms of cognitive impairment. With the growing availability of early diagnosis using imaging techniques and new biomarkers, there is hope that by increasing our understanding of the basic mechanisms which underlie the pathology we may actually be able to reverse what has hitherto thought to be an irrevocable process. With this comes a focus on the earliest changes likely to trigger the pathology, such as synaptic withdrawal which marks the loss of communication within neuronal pathways. A number of studies both in human brain and animal transgenic AD models show a significant loss of synapses; in mice this is evident very early in the pathology. The focus therefore has moved away from the importance of the amyloid plaques and neurofibrillary tangles in the disease process to the soluble Aβ oligomers and phosphorylated tau peptides.
2.2 Genetics of familial Alzheimer’s disease
The amyloid Aβ peptide present in parenchymal plaques or cerebrovascular deposits is a 4 kDa cleavage product of the amyloid precursor protein (APP), coded for by the APP gene. It has three main splice variants, APP770, 75, and 695, of which APP695 is the major neuronal form. APP is a multi-functional protein, important in development and synaptic plasticity. Although Aβ production occurs in normal neurons as well as those from AD, there are much higher brain levels of Aβ in AD, probably due to increased production or reduced clearance.
In autosomal dominant familial forms of AD (FAD), symptoms usually present earlier in life (i.e. before 60 years) and are due to mutations in one of three genes: APP, PSEN, or PSEN2 on chromosome 2, 4, or respectively. According to the Alzforum database <http://www.alzforum.org/mutations>, although many mutations are non-pathogenic, there are at least 25 APP pathogenic mutations, over 200 PSEN, and at least 6 PSEN2 clearly pathogenic mutations which lead to autosomal dominant forms of AD. Familial early-onset AD accounts for less than 5 per cent of cases of AD; however, the underlying mechanisms provide an indication as to how the majority of sporadic (isolated or non-clustering) AD cases may occur. Those living with Down’s syndrome (trisomy 2) usually develop AD symptoms and pathology by their 40s, and this
is thought to be due to the third copy of the APP gene provided by the extra chromosome 2. Thus gene duplication or the presence of mutations, which facilitate an increase in Aβ, result in AD pathology and consequent symptoms of cognitive dysfunction. Many of the FAD mutations present in the three aforementioned genes have been shown to result in an increase in total Aβ production or an increase in the Aβ-42:Aβ-40 ratio; that is, the two common forms of Aβ which comprise 42 and 40 amino acids respectively. This lends credence to the ‘amyloid hypothesis’ which suggests that all AD pathology and symptoms are derived from the toxic effects of Aβ, essentially by its overproduction or lack of clearance. Of the two forms, Aβ-42 has been shown to be more neurotoxic; it is usually found within parenchymal plaques as it has a propensity to aggregate more rapidly. Aβ-40 is found predominantly in the vasculature as it is sufficiently soluble to be cleared to the blood vessels before being deposited.
2.3 Processing of amyloid precursor protein
The ‘amyloidogenic’ route, by which Aβ is produced during the processing of APP, is described in Figure 2.2. In the normal brain this constitutes only a small part of
Figure 2.2 The processing of amyloid precursor protein (APP) to form Aβ.This schematic shows the APP770 splice variant, and amino acid residue numbers are derived from this. In the APP695 variant, most commonly found in neurons, the two N-terminal exon insertions are excluded. Cleavage may commonly occur by α-secretase in the plasma membrane or by β-secretase during recycling through the endosomal pathway. In normal neurons, the enzyme α-secretase cleaves APP about 90–95 per cent of the time to form the C-terminal peptide C83 (83 amino acids long), and the N-terminus called APPα (or soluble sAPPα). α-secretase comprises ADAM 9, 0, or 7. Normally, 5–0 per cent of the time, the enzyme β-secretase cleaves APP to form C99 and sAPPβ. Subsequently γ-secretase cleaves within the hydrophobic membrane to form the peptide p3 (non-amyloidogenic pathway) or Aβ (amyloidogenic pathway) respectively. The APP intracellular domain (AICD) produced in the non-amyloidogenic pathway is degraded, whereas the identical fragment produced in the amyloidogenic pathway is transferred to the nucleus where it acts as a transcription factor and is stabilized by adaptor proteins such as Fe65. One of the target genes for upregulation includes that for neprilysin.
the processing of APP protein, the rest is processed by the ‘non-amyloidogenic’ pathway where Aβ is not produced. The enzymes responsible for cleavage of APP are α-, β-, and γ-secretase. α-secretase (comprising three enzymes, known as ADAM 9, 0, and 7) are members of the ADAMs (A disintegrin and metalloprotease) family; ADAM 7 is also known as tumour necrosis factor-α (TNFα) converting enzyme or TACE. β-secretase cleavage is due to the activity of two aspartyl proteases, β-site APP cleaving enzyme (BACE) and 2, the former of these is most important in the brain. γ-secretase is a complex of four proteins, presenilin or 2, nicastrin, PEN2 (presenilin enhancer 2), and APha or APhb (anterior pharynx-defective phenotype ). Presenilin is the catalytic component of γ-secretase, responsible for cleaving the APP C-terminal peptide (C99 or C83) to form either Aβ or a non-toxic peptide, p3. This γ-secretase complex has a large number of substrates other than APP, such as Notch, low-density lipoprotein receptor-related protein (LRP), cadherins, ErbB4, and the cell-surface glycoprotein CD44. Mutations near the C-terminal region of Aβ (such as the ‘London’ mutation V77I) or mutations in PSEN or 2 lead to an increase in the Aβ-42:Aβ-40 ratio as this is the site of cleavage after either 40 or 42 residues. Conversely, the ‘Swedish’ double mutation at the N-terminus of the Aβ peptide results in an increase of both Aβ-40 and Aβ-42. This is because this mutant APP has an approximate hundredfold higher affinity for BACE than the normal APP protein.
2.4 The toxicity of A
β
2.4. Aβ: mitochondrial damage and calcium
Aβ, particularly the Aβ-42 form, has adverse effects on neurons and the cellular environment of the brain, and it is suggested that an accumulation of these effects over a long period of time eventually causes enough neuronal damage to generate symptoms consistent with AD. The brain has a high rate of oxygen consumption yet low levels of protective antioxidant enzymes and therefore is vulnerable to damage from oxidation and the reactive oxygen species (ROS) produced. Aβ accumulates intraneuronally in endosomes and lysosomes and disrupts protein degradation. Mitochondrial dysfunction also occurs early in the disease process and is related to the presence of Aβ Damage includes decreased mitochondrial membrane potential, loss of respiratory enzyme activity, production of ROS, and calcium dysregulation.
An important aspect of toxicity in the AD degenerative process is the control of calcium homeostasis and there are a number of processes which may facilitate an undesirable rise in intraneuronal Ca2+. Extracellular Aβ oligomers, in particular Aβ-42, have been shown to bind to normal cellular prion protein at the plasma membrane to increase entry of Ca2+ into the neurone. The APP intracellular domain (AICD) peptide may also be involved by affecting the sensitivity of the channels (InsP3 and ryanodine receptors (RYRs)) that cause Ca2+ levels to be released from internal stores. High levels of Ca2+ may also cause the mitochondria to release cytochrome C, with subsequent initiation of caspase cleavage and controlled cell death (apoptosis) and/or synapse reduction via long-term depression (LTD). At the mitochondrial membrane Aβ may also interact with cyclophilin D to form a mitochondrial permeability transition pore (mPTP) which contributes to leakage of mitochondrial constituents such as cytochrome C.
2.4.2 Aβ: binding partners and synaptic dysfunction
Aβ is able to bind many proteins and thus interfere with their expression and function. Amyloid β-peptide binding protein alcohol dehydrogenase (ABAD) is a binding
partner of Aβ. This enzyme is important in glucose-deficient environments and is able to increase the brain’s ability to use ketones, where it can be protective, as seen after a stroke. However, in the presence of Aβ, this normally protective enzyme is able to facilitate apoptosis. When ABAD is overexpressed in transgenic AD mouse models, the presence of Aβ results in spatial and temporal memory deficits. Aβ also binds the transcription factor cAMP-response element binding protein (CREB), which is important in formation of memory. CREB controls expression of a number of important proteins including brain-derived neurotrophic factor (BDNF), known to facilitate long-term potentiation (LTP), a correlate of memory formation. Notably, BDNF levels are reduced in AD brain and this fact alone probably contributes significantly to synaptic loss and memory dysfunction. Still under examination are the roles of Aβ oligomers and hyperphosphorylated tau in the profound synaptic dysfunction seen early in AD. The presence of Aβ is known to be associated with a decrease in the phosphorylation of glutamate N-methyl-D-aspartate (NMDA) receptor, which is required for LTP and synaptic strengthening. This results in an increase in receptor endocytosis and reduced LTP. Calcineurin (Ca2+-dependent protein phosphatase) is necessary for Aβ-induced spine loss and endocytosis of glutamate receptors. This suppression of LTP by Aβ can be prevented by inhibition of caspase-3. Tau appears to be required for some of the Aβ induced synaptic defects as its removal ameliorates some of the synaptic and behavioural deficits seen in animal models of AD.
2.4.3 Aβ: inflammation
The deposition of Aβ into parenchymal plaques acts as a catch-all for other molecules and eventually an inflammatory response may be invoked. As we age, the balance of immune capability shifts from the humoral cell-mediated immune response and antibody production to rely further on the innate response involving proinflammatory cytokine production. Therefore with continued Aβ production, activated microglia produce proinflammatory mediators, such as the cytokines interleukins and tumour necrosis factor-α (TNFα), upregulate the complement system and produce ROS and excessive amounts of nitric oxide (NO) by inducible nitric oxide synthase (iNOS) which leads to neuronal cell death.
2.4 Tau
Importantly, the production of Aβ is linked with the deposition of tau, thought by many to be the more important of the two peptides in terms of neuronal degeneration and its associated symptoms.
Mutations in the tau gene MAPT have not been shown to be a primary cause of AD. Tau mutations are usually seen in frontotemporal dementias (FTDPs) such as frontotemporal dementia with parkinsonism associated with chromosome 7 (FTDP-7); chromosome 7 has the MAPT gene within it. Those living with FTDP-7 have tau deposits but rarely amyloid plaques. It seems that Aβ is ‘upstream’ of NFT formation and that tau mutations circumvent this step and do not invoke excessive Aβ production. The protein tau is a microtubule-binding protein, keeping microtubules in an assembled state by stabilizing α- and β-tubulin strands and enabling axonal transport. Tau exists in six isoforms, each with three or four microtubule-binding domains in the middle region of the protein. Microtubules facilitate passage of cargo containing nutrients, neurotransmitters, etc., from the cell body to the axon by kinesin protein complexes and towards the cell body by dynein protein complexes. Tau prevents cargo
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CHAPTER VII
CORRECTION OF SPEECH DEFECTS
In addition to the ordinary faults and failings in speech possessed by many in common, there are the special and specific defects, such as stammering, stuttering, lisping, and the like. Every defective is to be pitied, as many professions and occupations are of such a nature as practically to bar men and women who cannot speak well. There are the social and ethical handicaps, also, to be considered, as well as that of economics. The defective speech of a child renders him the butt of his playmates’ rude and often brutal jokes. The sensitive is thus driven away from society. He becomes a solitary and not infrequently his life is ruined.
Speaking of the stutterer, one who is not afflicted by this disease (for so authorities have determined it to be), cannot realize what a terrible life he lives. Dr. Scripture, of Columbia University, New York City, who is one of the greatest authorities on this subject, says: “One boy often threw himself on the floor, begging his mother to tell him how to die. Another boy asked for a letter to his father, telling him to keep the other children from laughing at him. Many stutterers become so sensitive that they imagine everybody is constantly making fun of them. The life of a stutterer is usually so full of sorrow that it can hardly be said to be worth living.”[3]
The speech delinquent is shy, timid, super-sensitive, constantly harboring the thought that people are laughing at him. He gradually shuns society, lives unto himself, and in many instances becomes morally depraved. He contracts a morbid outlook upon life in general, and often is driven to criminality. This statement is no exaggeration. The Board of Education in New York City, after thorough investigation, found that “one school child in four suffers from speech defect,” and that “among boy criminals, nine in ten suffer from the same malady.”
In the Grand Rapids schools classes for the sole purpose of correcting speech defects were organized.
The mechanical arrangement was as follows: Twelve classes were arranged for in five different schools with a half hour a day for each class. The children were grouped according to age, kind of defect, etc., and a teacher with special training for the correction of speech was sent from school to school to give the instruction.
Our plans for this year (1918) are practically the same as for last excepting that we have more special teachers and will be able to reach a greater number of schools and give more time to individual cases.... During the school year of 1916-17, we had under instruction 107 children and obtained the following results:
This year we will have under instruction of our special teachers about 250 children, and in addition to this we hope to work for correction and prevention of speech-defects in general by giving instruction in voice culture and corrective phonetics to all of the children of the primary grades. This work will be done by the grade teachers under the supervision of the speech department.[4]
T P
A person with a slight impediment in his speech, due probably to some minor organic disorder, could be much helped by the average
teacher, if the latter would give this subject of speech serious consideration. Of course there are cases where, from birth, the child’s speech organs have been impaired, and again, disease or some surgical operation may have caused interference with their proper functioning. In such cases as these a speech specialist is needed and often medical aid as well.
We do not presume to suggest with any degree of authority just what to do and what not to do in such extremities, but rather to present a few fundamental and tried principles which have proved successful in many cases. There are two classes whose speech defects are due to some mental cause—the Stammerers and the Stutterers.
C S
The stammerer finds it extremely difficult to begin to make any audible vocal sound. He stares blankly at you with a very slight, if any, suggestion that he is trying to speak. For the time being he is a mute, with no power to speak, and yet with every means of speaking. This is a pitiful condition in which to be.
The next stage finds the stammerer able, after a snapping of his fingers, or bending of his knees, or lifting up of a foot, or swinging his arms, or after some similar bodily action, to speak along smoothly with no suggestion of an impediment for a considerable period of time, after which he again lapses into silence. The following characteristics are common to most stammerers:
1. He is inclined to speak too fast when started.
2. He has no control over his breathing.
3. He often endeavors to speak during inhalation instead of during exhalation.
4. He is extremely sensitive, always fearing that he is making a mistake.
5. His face usually carries an expression of bitter sorrow and despair.
6. He is usually intensely grateful to any one for a kind word of help.
7. He tries with the utmost skill to conceal his defect.
8. He is usually weak physically.
9. He is usually of a nervous temperament.
10. He usually possesses splendid courage and high ideals, which too often are destroyed because he cannot accomplish them with this weight of halting speech about his neck.
T S
The stutterer, unlike the stammerer, is able to make an audible sound at will. His difficulty lies in his inability to say more than one sound until he has repeated the initial sound from six to fifteen times. It seems that he must get up a certain amount of speech momentum: “B-b-b-bring me th-th-th-that b-b-b-book.” Or, “W-w-w-well, I think it is a v-v-v-very fine day.”
In a large measure the causes of stuttering and stammering are identical. Stammering is stuttering in the superlative degree. What is true of the stammerer is also true of the stutterer, with the exception that the stutterer is less melancholy, and less conscious of his defect.
For both, or either, practice in simple exercises is very necessary, but before specific training is given, the defective should be interviewed concerning his health. If a boy or girl is not given sufficient food and proper food (and such is often the case), there is small chance for speech improvement. Oftentimes it is found that these speech delinquents are playing too hard and wasting the nervous energy which should be utilized in mastering their vocal impediment.
The most successful way of handling these problems is to have the defectives placed in separate classes according to their particular needs and ages. Then get a physician’s diagnosis of each individual case. This diagnosis generally gives the special teacher the knowledge necessary for intelligent correction. The teacher must be patient, gentle, sympathetic and yet determined. She herself must possess ease and real enjoyment in speaking.
Practice Exercises
1. Speech defectives must first learn how to relax. They should spend at least ten minutes daily at home lying flat on their backs concentrating the mind on separate parts until the whole body is completely relaxed. This relaxation exercise can and should be carried on daily. At school, a similar though modified exercise should be attempted.
2. They must master diaphragmatic breathing. This exercise should follow the relaxation exercise, for the best results are obtained while lying on the back; the next best while sitting erect.
(a) Inhale slowly, filling lower lobes of lungs first, and then the upper part of chest. While doing this count ten mentally; exhale, counting ten mentally. Repeat five times.
(b) Inhale ten counts again, hold breath five counts, exhale ten counts. Repeat five times.
(c) Inhale slightly, then purse lips to impede the air as it passes out; now give one short puff with spasmodic contraction of abdomen. Repeat five times, inhaling slightly before each puff.
(d) Inhale deeply, then give one long puff with continuous contraction of the abdomen. Repeat five times, inhaling deeply before each puff.
3. Tone production should follow breathing exercises.
(a) Count orally 1-1-1-1-1 with spasmodic abdominal contraction. Repeat five times. Be sure that breath is taken in after each count.
(b) Count orally 1-1-1-1-1 with continuous abdominal contraction. Repeat five times.
(c) Inhale deeply and count orally 1 to 10, stressing every other count. Some students cannot do this unless the teacher keeps time with ruler as a baton, striking some object. Others can only do this by walking slowly, repeating a count on every other footfall. Repeat five times.
(d) Select a lyric with marked rhythm and read in concert in sing-song style. Repeat each stanza five times, giving marked pulsation to each accented syllable. Tennyson’s “Song of the Brook” is especially good for this purpose.
(e) Take a simple prose selection and mark it off in thought groups, and then read slowly and measuredly in concert, giving a fairly long pause between each group. Hamlet’s “Instructions to the Players,” and Lincoln’s “Gettysburg Address” are splendid for such work.
When the defective has learned to speak fluently memorized work, then he should be taught confidence in simple conversational exercises. This work should be, so far as possible, voluntary on the part of the pupil. Let the class form a circle, each one sitting with a sense of ease and relaxation and then, as they are inclined, take part in conversing on some simple, interesting topic. Some will have to be urged to participate while others find great delight in such work.
In regard to training in enunciation, this work has been found to be more successful when given late in the development of the defective. After he has gained confidence in speech ability and cultivated, to some degree, real enjoyment in voice production, he is better prepared to consider this more or less purely technical training. In very extreme cases, however, it will be found necessary to begin speech instruction with him as you would teach a child. Such
students must be taught the proper control of lips, tongue and jaw, as though they had never learned speech at all.
Experts who have devoted a lifetime to the study of speech evils and their remedy find a large variety of causes for them, as well as immense diversity in manifestation. One may seem to be born with a tendency to stammering, stuttering or lisping; another can trace the habit to a fright, to imitation, to some exhaustive disease, to nervous timidity, to self-consciousness. But whatever the cause, or however the evil manifests itself, it is a living nightmare, a dreadful, everpresent burden to its victim. Hence parents and teachers should seriously endeavor to correct the habit as speedily as it is discovered. For if it be long-continued it is almost sure to produce shyness, timidity, lack of necessary self-reliance, even moroseness, sullenness and other consequences of perpetual unhappiness.
At the outset let it be understood clearly that all harshness, unkindness, or severity of treatment in word or deed, adds to the evil and renders it more difficult of eradication. The victim of the habit is to be sympathized with, and lovingly encouraged. Yet promptness, firmness and persistency are essential in the production of a cure. The following suggestions should be put into practice, but seldom or never in the presence of strangers, or at any time when they would heighten the sufferer’s embarrassment. They must also be followed with happy cheerfulness.
1. When a victim of one of these habits begins to stammer or stutter, stop him immediately, and say pleasantly but firmly and crisply, “Stop!” Then command: “Take a deep breath! Now hold it! Now think of what you want to say—each word!” Then allow the stutterer to let out his breath; then inhale again deeply, and begin his speech. If he fails, see that he begins again. Practice this as often as you can. Exercises can also be made up, following the same procedure, that will be of incalculable benefit, as, for instance, taking a deep breath, then repeating as much of the alphabet as is possible before breathing again.
2. Cultivate slowness of speech. Insist upon words being spoken slowly, with great distinctness and clearness of articulation. The
moment stuttering begins, issue the commands: “Stop! Deep breath; think; breathe out, breathe in; now!” Let the teacher say his words very slowly and constantly encourage the pupil to do the same.
3. Cultivate the habit of rapid thinking. This can be done by a series of exercises played as games if necessary. For instance: “The Game of Names.” The teacher says, “Flower!” The pupil replies, “Rose.” If the teacher has a list ready he can call out his names as quickly as possible, such as, Animal, Tree, Water, Bird, Dog, etc., while the pupil responds, Horse, Oak, River, Sparrow, Bulldog, etc. The interest can be increased by repeating a generic term, requiring a different species for answer. Flower, Animal, Tree, Water, etc., can have a score or more of different answers.
Another exercise in prompt thinking is that of “Association of Ideas.” The teacher gives out a name—whatever occurs to him—as, for instance, “Tree.” The pupil immediately responds, “Leaves.” Then the teacher may add, “Autumn,” and the pupil, “Poetry,” and so on. Or the associations may all be required from the pupil. The words used as starters should be carefully chosen, of course, to meet the mental condition of the pupil; such words as Baby, Doll, Mamma, Bed, House, etc., being good for children of tender years.
Another excellent exercise is that of “Contrasts or Differences,” where the teacher says, “Boy,” and the pupil responds, “Girl.” “Black” calls forth “white,” “heavy” is responded to by “light,” etc.
Equally good is “Finishing Quotations” or “lines”—provided, of course, the pupil is old enough for such a mental exercise. For instance, the teacher says, “Everything is not gold,” while the pupil should respond, “That glitters.” “My country,” would bring out “’Tis of thee,” or “Right or wrong.”
Anything that quickens the intellect and demands ready response is of material help, but the teacher must not forget that, in this mental-promptness exercise, slow and deliberate speech also are essential on his part and that of the pupil.
4. Whenever it is found that a pupil stammers or stutters over a word beginning with a consonant, as, for instance, “bread,” require
him to drop out the initial letter and say “read,” or even “ead.” Such words as pie, Tommy, tub, butter, top, bank, tumble, tell, nut, lap, can be used. Let him say, “ie,” “ommy,” “ub,” etc. Then when he is sure of this part of the word, let him, after taking a deep breath, try the full word, saying it again, but always slowly and distinctly.
5. Teach the pupil to sing his sentences. Begin with some simple salutation, as, “Where are you going?” and let it be sung to the notes:
Listen | MusicXML
Where are you going? I’m go-ing home
Then let a response be sung reversing the music, “I’m going home.” “How do you do?” “Where are your father and your mother?” “How far is it to the market?” are sentences that can be sung. The teacher should invent his own music and words, but insist upon slow, deliberate utterances of tone and word. This is a wonderful help in certain kinds of cases.
6. There are certain simple exercises or calisthenics that materially aid in strengthening the muscles of the head, neck, throat, jaw, etc. The teacher can utilize these according to his best judgment. Any book of calisthenic or physical exercises will suggest those most useful.
7. But above all, in seeking a cure of these distressing evils, use the psychical or spiritual remedy Give the pupil confidence that God never intended him to be cursed by a stammering, stuttering, or lisping tongue. He is the child of an Infinite and Loving Father. All good is his, if he will learn how to take it. Urge him to restful, trustful reliance upon the tender help of the Great Power outside of himself, in conjunction with the efforts you and he together are making to effect a cure.
To the teacher who needs thorough preparation upon this subject we can commend heartily Dr. E. W. Scripture’s book “Stuttering and Lisping,” published by the Macmillan Company, New York.
CHAPTER VIII
ENUNCIATION AND PRONUNCIATION
The study of the subject of enunciation should come comparatively late in the development of the pupil, say, beginning with the fifth grade. There are other fundamentals that the pupil should be well grounded in before any definite concentration of effort should be put upon enunciation.
The majority of children and adults are backward in mastering the art of correct speaking, therefore, if the teacher begins by expecting the pupil to be accurate in enunciation, which is really one of the finishing touches, he is in danger of deadening forever the desire for self-expression and enjoyment in speaking.
Pronunciation should precede any drill in enunciation. The pupil is quick to grasp correctness in right pronunciation, and desires it fully, but he cares little for enunciation. Most pupils will shy just a little when you tell them that the proper way to pronounce, or rather to enunciate the word education is ed-u-ca-tion and not ed-ji-ca-tion. Or, take the vowel (a) as in ask, which should be pronounced (ạ). Invariably the untutored will give the vowel the extreme flat sound of (ă) as in hăt, and will think that he is affected if he give it the proper soft, broad sound. He will likely think this even if you compromise with the sounds.
So our policy has been to forego acute criticism in enunciation until the student has acquired considerable momentum in speechdesire. In other words, we are more interested, during his early studies, that he develop and cultivate the desire and will to express, than that he express himself accurately. Then, later, we gradually call his attention to his slovenly speech. Above all things let us beware of quenching the sacred fire of spontaneity, for without that all speech loses its charm and power. Is it not better that the student be stimulated to speech action, even though it be imperfect in some—
even in many—respects, than that he be conscious of all his defects and never speak at all?
Clearness and precision in enunciation and pronunciation mark the genuineness and strength of one’s character. Even the brightest person, if he mispronounce his words, is accused of mediocrity and is suspected of being unaccustomed to the society of refined and cultured people. There should be daily systematic drill in childhood when correct speech habits are most quickly and firmly established. Another great advantage of early training is that this is the period when the student is least self-conscious.
There are three essentials for clear and exact enunciation and pronunciation: First, an acute ear; second, diligent practice; and third, constant vigilance. These three essentials should be kept constantly in mind in carrying out the following exercises. We should first see that the student’s ear can detect the correct, pure resonances, and then pursue vigorous practice in them. At first this kind of exercise is tedious and irksome, but with accomplishment comes keen pleasure.
Let us begin with the vowel sounds. For the word exercises we shall take words often mispronounced as well as poorly enunciated. Thus we shall be doing two important things: cultivating the ear, and improving word production.
E O
The vowels are either long, short, or diphthongal. The resonances of the long vowels begin at the back, passing through the middle, to the front of the mouth. Thus:
The above represents the approximate and relative openings of the mouth in long vowels.
You notice the mouth aperture is narrow at the back, wide in the middle and narrow again at the front. For practice AW and AH and OO are the most valuable because the two chief difficulties of the student are; first, to open his mouth wide enough, and second, to keep his speech forward on the lips. Usually his speech is throaty. Practice the following in concert and individually in order to secure freedom in controlling the mouth:
1. Repeat E A AW AH O OO consecutively on the same pitch.
2. Change the pitch and repeat on each note of the scale.
3. Give a decided rising inflection to each vowel sound.
4. Give a decided falling inflection to each vowel sound.
5. Give a decided circumflex inflection to each vowel sound.
6. Blend them altogether by the straight inflection in a singing tone.
7. Laugh them He He He He, Ha Ha Ha Ha, Haw Haw Haw Haw, Hah Hah Hah Hah, Ho Ho Ho Ho, Hoo Hoo Hoo Hoo.
E T
In pronunciation there is a right and a wrong way. Some people are so desirous of appearing exact in this matter that they often introduce superfluous sounds. For example, such persons pronounce evil—ē´vĭl, instead of ē´vl; towards—tō-wŏrdz´ instead of tō´-erdz.
This habit of introducing an extra sound that is unnecessary reflects upon the learning of the individual quite as much as the neglecting of a sound that is necessary. Let us not attempt to foster extravagant niceties of speech, but let us cultivate in ourselves and our pupils an appreciation of, and a desire for, pure, substantial, and impressively spoken English, showing them that the real beauty of our language lies in its simplicity and its inherent, convincing power.
E
E P
Take up the exercises below in the following manner: First, discover the correct position of tongue, lips and jaw for producing the particular sound under consideration. Second, repeat the sound many times. See that you use your organs of speech properly in regard to the positions indicated at the beginning of each vowel exercise. After the repetition of each sound, let lips, tongue and jaw relax to normal position. Third, in repeating the words be sure the ictus or vocal stroke is properly and decidedly placed.
The main purpose is to develop pure vowel resonance, but inflectional freedom may be cultivated at the same time, if great care is taken not to interfere with the correct vocal positions of tongue, lips and jaw. Beware of a tendency in this direction. (See discussion of Inflection in another part of this book.)
K P
In showing the correct pronunciation of words in the following exercises, the simplest method has been adopted. The words are rewritten with a set of letters which have invariably the same sound and are familiar to everyone.
Webster’s New International Dictionary and Phyfe’s Words Often Mispronounced are the principal authorities consulted. The authors are greatly indebted to these works for help in determining correct pronunciation. The following table gives the diacritical marks used in the following pages:
ē ēve
[.=e] d[.=e]pend
ĕ bĕt ẽ hẽr e recent ī glīde
[.=i] [.=i]dea ĭ ĭt ō gō
[.=o] [.=o]bey ô absôrb ŏ hŏt ū blūe
[.=u] [.=u]nite û sûrge ŭ bŭt oo ooze oo book
Transcriber’s Note: [.=a] etc were printed as the letter with a macron above and a dot above that. These particular diacriticals are not used on any of the following pages, so the decision was taken not to attempt to represent them in any other way, because there are no corresponding precomposed characters in Unicode and font support for combining marks is often poor
The Vowel Sound as in “Awe”
Note: Tongue sags low and should not move; contact[5] is just a little over half way back of the middle of the mouth; mouth wide; lips well rounded. alder al´der, not ăl´der. almost—al´most, not al´must. also al´so, not ŏl´so.
always al´wāz, not al´wuz.
auction ak´shun, not ŏk´shun.
audience—a´dĭ-ens, not ŏ´jens.
cauliflower—ka´li-flow-er, not kŏ´li-flour.
caldron—kal´drun, not kŏ´drun.
Chaucer—Chau´ser, not Chŏw´ser.
Chicago—Shi-ca´gō, not Shi-kŏ´gō.
cornet—kôr´net, not kôr-net´.
exorbitant—egz-ôr´bi-tant.
falcon—fô´kn, not fŏl´kun. for—fôr, not fur.
ordeal—ôr´dēl, not ôr-dēl´.
ordinary—ôr´dĭn-ā-rĭ.
The Vowel Sound as in “Star”
Note: Tongue sags and is widened; contact is low and in center; mouth open wide; lips relaxed almost normally.
arctic—ärk´tĭk, not är´tĭk.
arduous—är´dū-ŭs.
armistice—är´mĭs-tĭs, not är-mĭs´tĭs.
bazar—ba-zär´.
encore—än-kor´, not ĕn´kor.
en route—än root´, not ĕn rout. far—fär, not fŭr.
father—fä´thẽr.
soprano—sō-prä´nō, not sō-prăn´ŏ.
staunch—stänch, not stănch.
taunt—tänt, not tănt.
tzar—zär.
tarlatan—tär´la-tan, not tarl´tan.
Parsifal—pär´sif-äl.
partisan—pär´ti-zăn.
particularly—pär-tik´yū-lẽr-lĭ.
The Vowel Sound as in “Ask”
Note: Tongue sags and is a trifle narrower than the above resonance in ä; mouth open wide; lips relaxed.
asked—åskt, not ăskt, nor ăst.
aversion—å-vẽr´shun, not a-ver´zhun.
bass (fish)—bås, not băs.
bath—båth, not băth.
chant—chånt, not chănt.
contrast (vb.)—kon-tråst´, not kon´trăst.
draft—dråft, not drăft.
draught—dråft, not drăft.
glass—glås, not glăs.
grant—grånt, not grănt.
grasp—gråsp, not grăsp.
mast—måst, not măst.
isinglass—ī´zĭng-glåss, not ī-zŭn´glăs.
pianist—pi-ån´ĭst, not pe´a-nist.
aft—åft, not ăft.
casket—kås´ket, not kăs´ket.
The Vowel Sound as in “Can”
Note: Tongue sags and widens; contact is front; mouth open moderately wide.
accept—ăk-sĕpt´, not ĕk-sept´.
accurate—ăk´kū-rat, not ăk´kẽr-ĭt.
algebra—ăl´je-bra, not ăl´je-brā.
ally—ăl-li´, not ăl´li (n) and (vb).
and—ănd, not ŭn, nor änd.
bade—băd, not bāde.
calcium—kăl´sĭ-ŭm, not kăl´shĭ-ŭm.
camera—kăm´e-ra.
canyon—kăn´yun.
catchup—kăch´up, not kĕch´up.
chasm—kăz´m, not kăz´um.
exact—egz-ăkt´, not eks-ăkt´.
flannel—flăn´nĕl, not flăn´nĕn.
harass—hăr´ăs, not har-răs´.
maritime—măr´ĭ-tĭm, not mâr´ĭ-tĭm.
olfactory—ŏl-făk´tō-rĭ, not ŏl-făk´trĭ.
The Vowel Sound as in “Fade”
Note: This is a diphthongal or double sound beginning on arch of tongue in middle of mouth and moving forward to just back of upper front teeth; mouth is open wide for first resonance but narrows for second.
aeronaut—ā´ẽr-ō-nat.
amiable—ā´mĭ-a-bl.
apparatus—ăp-pa-rā´tŭs, not ăp-pa-ră´tus.
apricot—ā´prĭ-cŏt, not ă´prĭ-cŏt.
chaos—kā´ōs.
Danish—dā´nĭsh, not dă´nĭsh.
data—dā´ta, not dă´ta.
disgrace—dĭs-grās´.
heinous—hā´nŭs, not hē´nŭs.
naked—nā´kĕd, not nĕ´kĕd.
acorn—ā´kŭrn, not ā´kŏrn.
patriotic—pā´trĭ-ŏt-ĭk, not păt´rĭ-ŏt-ĭk.
plague—plāg, not plĕg.
slake—slāk, not slăk.
wary—wā´rĭ, not wâ´ri.
ignoramus—ĭg-nō-rā´mŭs, not ĭg-nō-ră´mŭs.
The Vowel Sound as in “Led”
Note: Tongue arched; contact at top of arch; mouth moderately open; lips relaxed.
access—ăk´sĕs, or ăk-sĕs´.
address—(n) and (vb) ad-drĕs´.
cemetery—sĕm´ē-tĕr-ĭ, not sĕmĭ-trĭ.
centennial—sĕn-tĕn´nĭ-al.
equipage—ĕk´wĭ-pāj, not ĕ-kwĭp´ĕj.
equitable—ĕk´wĭ-ta-bl, no ĕ-kwĭ´ta-bl.
every—ĕv´ẽr-ĭ, not ĕv´rĭ.
evident—ĕv´ĭ-dĕnt, not ĕv´ĭ-dŭnt.
excellent—ĕk´sĕl-ĕnt, not ĕk´slŭnt.
preface—(n) and (vb) prĕf´ās.
legislature—lĕj´ĭs-lāt-yŭr
exit—ĕks´it, not ĕgz´it.
exist—ĕgz-ĭst´, not ĕks´ĭst.
irreparable—ĭr-rĕp´a-ra-ble, not ĭr-rē-păr´a-bl.
generally—jĕn´ẽr-al-ĭ.
instead—ĭn-stĕd´, not ĭn-stĭd´.
The Vowel Sound as in “We”
Note: Tongue arched to upper forward position; mouth aperture narrow. This is a single vowel resonance.
