Alzheimer's Disease / Dementia

Epidemiology

Alzheimer's disease is the commonest cause of senile dementia.

The prevalence is about 1% at age 60, rising rapidly to 40-50% after the age of 85. It is slightly more common in women.

Pathophysiology

Pathologically, the brain is atrophic; the characteristic microscopical features are loss of cortical neurones with amyloid plaques and neurofibrillary tangles.

The cause of Alzheimer's disease is unknown. Genetic factors are important in some cases; the apolipoprotein E4 gene has been studied intensively. Familial Alzheimer's disease has been associated with genes encoding amyloid precursor protein on chromosome 21 and a separate gene locus on chromosome 14.

People with Down's syndrome (trisomy of chromosome 21) develop Alzheimer's disease, if they survive over the age of 40 years.

Clinical Features

Memory loss is usually the first symptom; it is often noted by family and friends before the patient. It begins with "short-term" memory. "I asked him to change the light bulb. I had to ask again 10 minutes later and he denied I had spoken to him". Taken in isolation, such an event is within the fabric of normal daily life. However, slowly over the subsequent months or years a pattern emerges of consistently forgetting new information. This has a dramatic effect on daily life.

Long-term memory, "the memory of things past", is eroded and other interlinked cognitive functions become involved. Language problems may begin with word finding difficulty, followed by the gradual loss of comprehension of the spoken word, reading and writing. The speech production may remain "fluent" but progressively "makes less sense"; a pattern referred to as receptive or fluent dysphasia. Sometimes language features dominate the presentation; this subtype is labelled primary progressive aphasia.

Other areas of cognition which are impaired include:

• Attention span: difficulty in continuing to perform a specific activity, eg counting from 1-20, listening to the wife speak

• Calculation: difficulty in addition, subtraction etc

• Ideational apraxia: difficulty in performing a complex motor task due to a loss of understanding of what is involved, eg wiring a plug, getting dressed

• Visuo-spatial: difficulty in recognising objects, people and other subtle aspects of visual perception, eg getting lost while driving or walking around the house, inability to recognise faces. visual perspective. given the presence of normal power and sensation.

There is an associated change in personality and behaviour. "I've lost the man I married 40 years ago".

Depression is common as are visual hallucinations. Verbal and physical aggression towards family and carers is not infrequent.
Investigation

The exclusion of potentially treatable causes of dementia is important; blood tests are done to check for easily identifiable and treatable conditions including hypothyroidism, B12 deficiency and neurosyphilis, although the latter is rare in the Ireland nowadays.

Depression may mimic dementia and should be actively screened out. Imaging the head (with CT or MR scanning) may be indicated in some cases if there is a suspicion of hydrocephalus (dementia, ataxia and urinary incontinence) or tumour (progressive focal onset). Examination of the CSF and other more esoteric tests are done in selected cases.

In a younger age group (under 60 years) or if the history is short, the possibility of vasculitis, HIV infection or CJD may need to be considered. Cerebrovascular disease causing multi-infarct dementia and Lewy body dementia, associated with Parkinsons disease, are the commonest differential diagnoses.


Written by Medpages Editorial Team
Last Editorial Review: 21/1/2010