ArticlesSmoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study
Introduction
The prevalence of dementia increases greatly with age: at least 30% of people aged 85 years and older have the disorder.1 Alzheimer's disease and vascular dementia are the main subtypes of dementia, and account for about 90% of affected patients.1 Smoking is a risk factor for vascular disease, including atherosclerosis and thrombosis, and increases the risk of vascular dementia.2, 3 Reduction of cerebral perfusion is an acute effect of cigarette smoking and may be harmful in elderly people with a compromised cerebral circulation.4 Vascular involvement is probably more important than previously thought in the pathogenesis of Alzheimer's disease.5, 6, 7 Nonetheless, an inverse association has been reported between smoking and Alzheimer's disease.8 Van Duijn and colleagues9 showed that in early-onset Alzheimer's disease, the possible protective effect of smoking was limited to carriers of the apolipoprotein €4 (APOE4) allele. Although there are several possible explanations for a protective effect of smoking on Alzheimer's disease,8, 9 this finding in previous studies could reflect bias.10 Smoking also strongly increases risk of premature death, and those smokers who survive to old age may be a more selected group than non-smokers of similar age.11
In this prospective population-based study we examined the association of cigarette smoking with dementia and Alzheimer's disease, and whether this relation depended on age, sex, and the APOE genotype.
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Study design and population
The Rotterdam Study is a community-based prospective cohort study of individuals aged 55 years and older,12 which was undertaken with the approval of the local medical ethics committee. All 10 275 residents of a Rotterdam suburb who were older than 55 years were eligible. 7983 (78%) residents agreed to take part and gave their informed consent and permission for us to obtain medical information from their family doctor and medical specialists. Baseline examinations took place between 1990 and
Results
Table 1 shows the baseline characteristics of the study population. The mean follow-up was 2·1 years (range 1·5–3·4), and included 14 761 person-years of observation. During follow-up, 429 (6·2%) of the 6870 participants died and 962 (14·0%) were not re-examined because of refusal or severe illness. We detected 146 incident cases of dementia, of which 105 (72%) were Alzheimer's disease and 19 (13%) were vascular dementia. The incidence rates of dementia per 1000 person-years for the age-groups
Discussion
In this large prospective population-based study, people who smoked cigarettes were at increased risk of dementia and Alzheimer's disease. This increased relative risk of dementia was greatest in smokers without the APOE4 allele. By contrast, smokers with this allele did not have an increased risk of dementia.
Our study has several advantages over previous studies on smoking and dementia.8 We avoided selection bias because the study was prospective and population based with a high response rate
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