|Alzheimer's disease is a primary
degenerative cerebral disease of unknown ethiology, with
characteristic neuropathological and neurochemical
features. It is usually insidious in onset and develops
slowly but steadily over a period of years. This period
can be as short as 2 or 3 years, but can occasionally be
considerably longer. The onset can be in middle adult
life or even earlier (Alzheimer's disease of presenile
onset), but the incidence is higher in later life (Alzheimer's
disease of senile onset). In cases with onset before the
age of 65-70, there is the likelihood of a family history
of a similar dementia, a more rapid course, and
prominence of features of temporal and parietal lobe
damage, including dysphasia or dyspraxia. In cases with a
later onset, the course tends to be slower and to be
characterized by more general impairment of higher
cortical functions. Patients with Down's syndrome are at
high risk of developing Alzheimer's disease.
There are characteristic changes in the brain: a marked reduction in the population of neurons, particularly in the hippocampus, substantia innominata, locus ceruleus, and temporoparietal and frontal cortex; appearance of neurofibrillary tangles made of paired helical filaments; neuritic (argentophil) plaques, which consist largely of amyloid and show a definite progression in their development (although plaques without amyloid are also known to exist); and granulovacuolar bodies. Neurochemical changes have also been found, including a marked reduction in the enzyme choline acetyltransferase, in acetylcholine itself, and in other neurotransmitters and neuromodulators.
As originally described, the clinical features are accompanied by the above brain changes. However, it now appears that the two do not always progress in parallel: one may be indisputably present with only minimal evidence of the other. Nevertheless, the clinical features of Alzheimer's disease are such that it is often possible to make a presumptive diagnosis on clinical grounds alone.
Dementia in Alzheimer's disease is at present irreversible.
The following features are essential for a definite diagnosis:
(a) Presence of a dementia as described above.
(b) Insidious onset with slow deterioration. While the onset usually seems difficult to pinpoint in time, realization by others that the defects exist may come suddenly. An apparent plateau may occur in the progression.
(c) Absence of clinical evidence, or findings from special investigations, to suggest that the mental state may be due to other systemic or brain disease which can induce a dementia (e.g. hypothyroidism, hypercalcaemia, vitamin B12 deficiency, niacin deficiency, neurosyphilis, normal pressure hydrocephalus, or subdural haematoma).
(d) Absence of a sudden, apoplectic onset, or of neurological signs of focal damage such as hemiparesis, sensory loss, visual field defects, and incoordination occurring early in the illness (although these phenomena may be superimposed later).
In a certain proportion of cases, the features of Alzheimer's disease and vascular dementia may both be present. In such cases, double diagnosis (and coding) should be made. When the vascular dementia precedes the Alzheimer's disease, it may be impossible to diagnose the latter on clinical grounds.