Smoking and risk of dementia and Alzheimerʹs disease in a population-based cohort study: the Rotterdam Study

Background Previous studies suggested a protective effect of smoking on Alzheimerʹs disease, but most were case-control studies based on prevalent cases. The findings of prospective studies on the association between smoking and the risk of dementia are inconclusive. Methods We did a population-based follow-up study of elderly people who were initially free of dementia. 6870 people aged 55 years and older agreed to take part. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers. During follow-up, we recorded all incident cases of dementia. We used never smokers as the reference category to calculate relative risks of dementia and Alzheimerʹs disease by Cox proportional hazards regression, after adjustment for age, sex, education, and alcohol intake. We also examined modification of risk by age, sex, and the apolipoprotein E (APOE) genotype. Findings During mean follow-up of 2•1 (range 1•5–3•4) years, 146 incident cases of dementia were detected, of which 105 were Alzheimerʹs disease. Compared with never smokers, smokers had an increased risk of dementia (relative risk 2•2 [95% CI 1•3–3•6]) and Alzheimerʹs disease (2•3 [1•3–4•1]). Smoking was a strong risk factor for Alzheimerʹs disease in individuals without the APOE€4 allele (4•6 [1•5–14•2]), but had no effect in participants with this allele (0•6 [0•1–4•8]). Interpretation Smoking was associated with a doubling of the risk of dementia and Alzheimerʹs disease. Our finding that carriers of the APOE€4 had no increased risk of dementia suggests an interaction between smoking and the APOE€4 genotype in the aetiology of Alzheimerʹs disease.