Vascular disorders have been implicated in dementia, but whether atherosclerosis is
related to the most frequent type of dementia, Alzheimer's disease, is not known.
The apolipoprotein-E genotype has been associated with Alzheimer's disease, and we
postulate that it plays a part, together with atherosclerosis, in the aetiology of
Alzheimer's disease. We investigated the frequency of dementia and its subtypes in
relation to atherosclerosis and apolipoprotein E.
We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimer's
disease, and 1698 individuals who were not demented. Indicators of atherosclerosis
included vessel wall thickness and plaques of the carotid arteries, assessed by ultrasonography,
and the ratio of ankle-to-brachial systolic blood pressure as a measure of generalised
atherosclerosis. Based on these indicators participants were scored from 0 (no atherosclerosis)
to 3 (severe atherosclerosis) for degree of atherosclerosis. Apolipoprotein-E polymorphisms
were assessed in 246 patients and in 928 controls.
All indicators of atherosclerosis were associated with dementia (odds ratios ranging
from 1.3 to 1.9) and its major subtypes Alzheimer's disease (odds ratios 1.3-1.8)
and vascular dementia (odds ratios 1.9-3.2). The frequencies of all dementia. Alzheimer's
disease, and vascular dementia increased with the degree of atherosclerosis. The odds
ratio for Alzheimer's disease in those with severe atherosclerosis compared with those
without atherosclerosis was 3.0 (95% CI 1.5-6.0; p = 0.001). In participants with
the apolipoprotein-E epsilon 4 genotype and an atherosclerosis score of 2 or 3 the
odds ratio for all dementia was 4.5 (2.0-10.1; p < 0.001), for Alzheimer's disease
was 3.9 (1.6-9.6; p = 0.002), and for vascular dementia was 19.8 (4.1-95.0; p < 0.001).
These findings suggest that dementia and its two major subtypes Alzheimer's disease
and vascular dementia are associated with atherosclerosis and that there is an interaction
between apolipoprotein E and atherosclerosis in the aetiology of Alzheimer's disease.