Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimerʹs disease in the Rotterdam Study

Background Vascular disorders have been implicated in dementia, but whether atherosclerosis is related to the most frequent type of dementia, Alzheimerʹs disease, is not known. The apolipoprotein-E genotype has been associated with Alzheimerʹs disease, and we postulate that it plays a part, together with atherosclerosis, in the aetiology of Alzheimerʹs disease. We investigated the frequency of dementia and its subtypes in relation to atherosclerosis and apolipoprotein E. Methods We did a population-based study of 284 patients with dementia, 207 of whom had Alzheimerʹs 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. Findings All indicators of atherosclerosis were associated with dementia (odds ratios ranging from 1•3 to 1•9) and its major subtypes Alzheimerʹs disease (odds ratios 1•3–1•8) and vascular dementia (odds ratios 1•9–3•2). The frequencies of all dementia, Alzheimerʹs disease, and vascular dementia increased with the degree of atherosclerosis. The odds ratio for Alzheimerʹs 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 ε4 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 Alzheimerʹs 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). Interpretation These findings suggest that dementia and its two major subtypes Alzheimerʹs disease and vascular dementia are associated with atherosclerosis and that there is an interaction between apolipoprotein E and atherosclerosis in the aetiology of Alzheimerʹs disease.