title: Atherosclerosis, apolipoprotein E, and prevalence of dementia and Alzheimer's disease in the Rotterdam Study.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Biostatistics, Erasmus University Medical School, Rotterdam, Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: A
authors.initials: A
authors.lastname: Ott
authors.forename: M M
authors.initials: MM
authors.lastname: Breteler
authors.forename: M L
authors.initials: ML
authors.lastname: Bots
authors.forename: A J
authors.initials: AJ
authors.lastname: Slooter
authors.forename: F
authors.initials: F
authors.lastname: van Harskamp
authors.forename: C N
authors.initials: CN
authors.lastname: van Duijn
authors.forename: C
authors.initials: C
authors.lastname: Van Broeckhoven
authors.forename: D E
authors.initials: DE
authors.lastname: Grobbee
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000209:etiology*; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000150:complications* / Q000453:epidemiology; D003430:Cross-Sectional Studies; D003704:Dementia / Q000453:epidemiology / Q000209:etiology; D015140:Dementia, Vascular / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D015995:Prevalence
chemical_list: D001057:Apolipoproteins E