Alzheimer's disease

Alzheimer's disease (AD), a neurodegenerative disease, is the most common cause of dementia and characterized clinically by progressive intellectual deterioration together with declining activities of daily living and neuropsychiatric symptoms or behavioral changes. The most striking early symptom is memory loss (amnesia), usually manifest as minor forgetfulness that becomes steadily denser with illness progression, with relative preservation of older memories. more...

As the disorder progresses, cognitive (intellectual) impairment extends to the domains of language (aphasia), coordinated movement (apraxia), recognition (agnosia) and those functions (such as decision-making and planning) closely related to the frontal lobe of the brain, reflecting extension of the underlying pathological process. This consists principally of neuronal (cell) loss (or atrophy), together with deposition of amyloid plaques and neurofibrillary tangles. Genetic factors are known to be important, and polymorphisms (variations) in three different autosomal dominant genes - Presenilin 1, Presenilin 2, and Amyloid Precursor Protein - have been identified that account for a small number of cases of familial, early-onset AD. For late onset AD (LOAD), only one susceptibility gene has so far been identified - the epsilon 4 allele of the APOE gene. Age of onset itself has a heritability of around 50%.

History

The symptoms of the disease as a distinct entity were first identified by Emil Kraepelin, and the characteristic neuropathology was first observed by Alois Alzheimer, a German psychiatrist, in 1906. In this sense, the disease was co-discovered by Kraepelin and Alzheimer, who worked in Kraepelin's laboratory. Because of the overwhelming importance Kraepelin attached to finding the neuropathological basis of psychiatric disorders, Kraepelin made the generous decision that the disease would bear Alzheimer's name (J. Psychiat. Res., 1997, Vol 31, No. 6, pp. 635-643).

For most of the twentieth century, the diagnosis of Alzheimer's disease was reserved for individuals between the ages of 45-65 who developed symptoms of presenile dementia, which was considered to be a more or less normal outcome of the aging process. In the 1970s and early 1980s, however, the name "Alzheimer's disease" began to be used, within and outside the medical profession, equally for individuals age 65 and older with senile dementia, and was eventually adopted formally for all individuals with the common symptom pattern and disease course in the psychiatric and neurological nomenclature.

Clinical features

The usual first symptom noticed is memory loss which progresses from seemingly simple and often fluctuating forgetfulness (with which the disease should not be confused) to a more pervasive loss of recent memory, then of familiar and well-known skills or objects or persons. Aphasia, disorientation and disinhibition usually accompany the loss of memory. Alzheimer's disease may also include behavioral changes, such as outbursts of violence or excessive passivity in people who have no previous history of such behavior. In the later stages, deterioration of musculature and mobility, leading to bedfastness, inability to feed oneself, and incontinence, will be seen if death from some external cause (e.g. heart attack or pneumonia) does not intervene. Average duration of the disease is approximately 7-10 years, although cases are known where reaching the final stage occurs within 4-5 years, or up to 25 years.

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