Elsevier

The Lancet

Volume 349, Issue 9046, 18 January 1997, Pages 151-154
The Lancet

Articles
Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study

https://doi.org/10.1016/S0140-6736(96)09328-2Get rights and content

Summary

Background

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.

Methods

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.

Findings

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 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 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).

Interpretation

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.

Introduction

Dementia is an important cause of disability, particularly in the elderly. The most important subtype of dementia is Alzheimer's disease, which accounts for at least half of all dementia cases.1 The causes of dementia are largely unknown, although important progress has been made in discovering genetic factors that play a part in the aetiology of Alzheimer's disease. In particular, an association of the apolipoprotein-E ε4 allele with Alzheimer's disease has been reported.2, 3, 4 Atherosclerosis has been implicated in dementia, but except for a small group of patients diagnosed as having vascular dementia, no evidence for a role of atherosclerosis in other dementias including Alzheimer's disease, has been presented.5 Non-invasive techniques to assess atherosclerosis allow the study of atherosclerosis and its putative sequelae in large populations.

We report a population-based cross-sectional study of atherosclerosis, the apolipoprotein-E genotype and the prevalence of dementia and its subtypes in 284 dementia patients and 1698 individuals who were not demented.

Section snippets

Methods

This study was done as part of the Rotterdam Study, a single-centre prospective follow-up study in which all residents aged 55 years or over from the suburb of Ommoord in Rotterdam, Netherlands, were invited to take part. The study was approved by the Medical Ethics Committee of Erasmus University, and written informed consent was obtained from all participants. The objective of the study was to investigate determinants of chronic and disabling cardiovascular, neurodegenerative, locomotor, and

Results

There were 82 men and 202 women with dementia. 207 (73%) demented patients were diagnosed as having Alzheimer's disease, 50 (18%) as having vascular dementia, and 27 (10%) as having other dementias. Table 1 presents some characteristics of the participants.

All indicators of atherosclerosis were significantly associated with all dementia (odds ratios ranging from 1·3 to 1·9; table 2), with Alzheimer's disease (odds ratios 1·3–1·8), and with vascular dementia (odds ratios 1·9–3·2). When patients

Discussion

The main findings of this study are that indicators of atherosclerosis are associated with the presence of dementia, and both of its main subtypes, Alzheimer's disease and vascular dementia, and that the association between atherosclerosis and dementia is particularly strong in those with the apolipoprotein-E ε4 genotype. However, limitations of the study design should be discussed.

This is a cross-sectional study, and changes in the atherosclerotic status could have occurred as a consequence of

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