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Alzheimer’s disease and other dementias 

Alzheimer’s disease and other dementias

Alzheimer’s disease and other dementias

John R. Hodges

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date: 27 April 2017

Dementia is defined as a syndrome consisting of progressive impairment in memory and at least one other cognitive deficit (aphasia, apraxia, agnosia, or disturbance in executive function) in the absence of another explanatory central nervous system disorder, depression or delirium.

Epidemiology and classification

Prevalence—dementia is common, affecting about 8% of all people over 65 years, rising to around 20% of those over 85 years. It is estimated that the 18 million people with dementia worldwide will increase to 34 million by the year 2025, with this increase being most marked in the developing countries.

Classification—dementia may be classified in terms of (1) its cause—these are many diseases, some of which are remediable and thus justify investigation (e.g. vitamin B12 deficiency, thyroid hormone deficiency), but most cases result from Alzheimer’s disease, vascular disorders, or subcortical diseases of the brain; or (2) according to the pattern of cognitive loss—this alternative perspective may contribute usefully to diagnosis, to the level of care required, and allow refinement of prognosis.

Particular causes of dementia

Alzheimer’s disease—the most common cause of dementia, probably caused by cerebral accumulation of the Aβ‎ fragment of the amyloid precursor protein. The initial cognitive deficit is impairment of episodic memory (see Chapter 24.4.1), which is thought to reflect the earliest site of pathology in the medial temporal lobe structures. Progression of disease is marked by failing memory, increasing disability in managing complex day-to-day activities, mental inflexibility, and poor concentration, eventually leading on to language and visuospatial impairments, apraxia, and failure of semantic memory. Neuropsychiatric symptoms are common and behavioural problems can be prominent. Agitation, restlessness, wandering, and disinhibition cause considerable carer burden. Terminal stages are characterized by reduced speech, ambulatory difficulties, dependence, and incontinence. The mainstay of treatment is social support and increasing assistance with day-to-day activities. Cholinesterase inhibitors generally achieve modest improvements in cognition in around 25 to 50% of patients.

Frontotemporal dementia—increasingly recognized as a common cause of dementia, particularly in younger patients. Usually associated with tau or ubiquitin-positive interneuronal inclusions. Clinical presentation is with progressive changes in personality and behaviour, or (less commonly) with progressive aphasia. There is no specific treatment.

Dementia with Lewy bodies—a common cause of dementia in the elderly. Typical presentation is with progressive cognitive decline, paralleling that seen in Alzheimer’s disease, but with (1) marked spontaneous fluctuations in cognitive abilities; (2) visual hallucinations; (3) spontaneous parkinsonism; and (4) exquisite sensitivity to neuroleptic medication. May respond to treatment with cholinesterase inhibitors, but neuroleptic drugs should be avoided whenever possible.

Vascular dementias—a wide variety of vascular diseases can affect the brain, with the most important vascular syndromes being (1) large infarcts, (2) lacunar infarcts, (3) small-vessel disease (Binswanger’s disease), (4) cerebral amyloid angiopathy, and (5) cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL).

Subcortical dementias—these include (1) Huntington’s disease, (2) progressive supranuclear palsy, (3) Parkinson’s disease, and (4) corticobasal degeneration.

Treatable causes of dementia—these include (1) normal-pressure hydrocephalus—the classic triad of presenting features comprises cognitive impairment, gait disturbance and incontinence; (2) chronic subdural haematomas; (3) benign tumours; (4) metabolic and endocrine disorders—including hypothyroidism, Addison’s disease, and hypopituitarism; (5) deficiency states—including vitamin B12 deficiency; and (6) infections—including neurosyphilis and HIV infection.

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