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Introduction to Alzheimerās Disease
OVERVIEW
Alzheimerās disease (AD) is a chronic, progressive, neurodegenerative disease that affects the brain. It mainly occurs in older people and involves progressive declines in memory and other cognitive functions. The brains of people with AD are characterised by shrinkage due to neuronal loss, the presence of plaques composed of the insoluble protein beta-amyloid, and the accumulation of an abnormal form of the protein tau to form neurofibrillary tangles. Management with conventional medicine mainly uses acetylcholinesterase (AChE) inhibitors and/or memantine combined with supportive care. This chapter describes the features of AD, pathological processes, diagnosis and management with conventional medicine.
Definition of Alzheimerās Disease
Alzheimerās disease (AD) is a degenerative brain disease that involves progressive decline in memory, language, problem-solving and other cognitive skills due to neuronal damage. This affects a personās ability to perform activities of daily living (ADL) and may be accompanied by personality changes and behavioural disturbances.1,2 AD is named after the anatomist Alois Alzheimer who reported histopathological changes in the brain of a patient named Auguste D, who had died in 1906 aged 51 years after having been admitted to the Frankfurt hospital in Germany suffering from progressive memory loss, delusion and hallucinations. Using a silver staining method, he identified the neuritic plaques and neurofibrillary tangles which have become defining pathological changes in brains affected by AD.3
Vernacular terms including ādementiaā and āsenile dementiaā are used to refer to AD, however, AD has received the following internationally recognised formal names and definitions:
ā¢Alzheimerās disease: NINCDS-ADRDA criteria developed by National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and the Alzheimerās Disease and Related Disorders Association (ADRDA).4
ā¢Dementia in Alzheimerās disease: International Statistical Classification of Diseases and Related Health Problems (ICD 10) (codes F00.0, F00.1, F00.2, F00.8).5
ā¢Dementia of the Alzheimerās Type: Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM 4-TR).6
ā¢Neurocognitive disorder due to Alzheimerās disease: Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5).7
Since a definite diagnosis of AD requires verification of AD pathology via autopsy or invasive tests, the categories āpossibleā, āprobableā and ādefiniteā Alzheimerās disease depending upon the diagnostic evidence and level of diagnostic certainty are included in the NINCDS/ADRDA criteria.4
In this monograph the term AD is used throughout except when specific sources are referenced or quoted.
Clinical Presentation
The onset of AD is insidious with gradual progression over a number of years without prolonged plateaus. In mild AD the typical clinical presentation is in persons of advanced age who have impairment in memory, learning and cognition which may be accompanied by disturbance in executive function. However, nonamnestic variants are present that involve visuospatial impairments or progressive logopenic aphasia.7,8
Mild neurocognitive disorder (NCD) due to Alzheimerās disease manifests typically with impairment in memory and learning, sometimes accompanied by deficits in executive function. At the major NCD phase (moderate to severe) there are also impairments in visuoconstructional/perceptual motor ability and language, whereas social cognition and procedural memory (e.g. dancing, playing musical instruments) tend to be preserved until the later stages of the disease.7,8 In the late stage of AD there are gait disturbances, aphasia, dysphagia, incontinence, myoclonus, and seizures. Pneumonia and loss of ability to swallow leading to aspiration are frequent causes of death.2,7
Depression and/or apathy are often evident earlier in the course of the disease and common features of the moderate to severe stages are psychotic features, irritability, agitation, combativeness, and wandering.7 These non-cognitive behavioural and psychological symptoms of dementia (BPSD) are experienced by up to 90% of patients at some time during the course of the disease.9
Epidemiology of Dementia and Alzheimerās Disease
Dementia was estimated to affect over 35 million people worldwide in 2010 and this number was predicted to double in 20 years.10,11 In China, the estimated number of people with dementia (all types) in 1990 was 3.68 million (1.93 million with AD) and in 2010 it was estimated to have grown to 9.19 million (5.69 million with AD).12
AD is the most common type of dementia in the United States (US) comprising 60ā80% of cases although a proportion of these suffer from mixed forms of dementias.2 It is estimated that in the US in 2010, 4.7 million individuals aged 65 years or older had AD.13
The prevalence of AD rises steeply according to age group with US census data suggesting the following proportions of individuals with a diagnosis of AD in the following age groups: 65ā74 years (7%), 75ā84 years (53%) and 85 years and older (40%).7 In a review of 39 epidemiological studies conducted in Europe and US, Takizawa (2015) reported variation in incidence from country to country, which may be due to differences in classification rather than population differences, with a prevalence range of 3% to 7%. Prevalence is higher in women than in men with almost two thirds of AD sufferers in the US being women.7,14
Burden of Alzheimerās Disease
In terms of cost, AD is associated with a high social and economic burden. For example, the burden has been reported to be heaviest on caregivers in the earlier stages of the disease (44ā69 hours per week in moderate AD), shifting to institutions at severe stages with considerable variation in medical cost estimates from country to country.14
Risk Factors
The lifetime risk of having developed AD at age 65 was one in six (17%) for women and for men it was one in eleven (9%). However it is likely that AD is underdiagnosed and the higher prevalence in women is influenced by the higher longevity of women.2 Other risk factors include family history, history of traumatic brain injury (TBI), cardiovascular disease and related conditions (diabetes, midlife hypertension, midlife obesity, smoking), physical inactivity, level of education and social engagement, mild cognitive impairment (MCI) and depression.2,15
Genetic mutations are estimated to account for about 1% of AD cases, particularly mutations in the genes for amyloid precursor protein (APP), presenilin 1 (PSENl), or presenilin 2 (PSEN2) which lead to early onset AD. Mutations in the apolipoprotein E (APOE) gene can also increase the risk of AD. Those with a history of a moderate traumatic brain injury (TBI) have twice the risk of developing dementia while the risk is 4.5 times in those who had a severe TBI.2,7,15,16 It is estimated that potentially modifiable risk factors are involved in about one third of AD cases worldwide.15
Pathological P...
