Smoking Is Associated with an Increased Risk of Dementia: A Meta-Analysis of Prospective Cohort Studies with Investigation of Potential Effect Modifiers

Abstract

BackgroundPrevious studies showed inconsistent results on the association of smoking with all-cause dementia and vascular dementia (VaD), and are limited by inclusion of a small number of studies and unexplained heterogeneity. Our review aimed to assess the risk of all-cause dementia, Alzheimer’s disease (AD) and VaD associated with smoking, and to identify potential effect modifiers.Methods and FindingsThe PubMed, Embase, Cochrane Library and Psychinfo databases were searched to identify studies that provided risk estimates on smoking and incidence of dementia. A random-effects model was used to yield pooled results. Thirty-seven studies were included. Compared with never smokers, current smokers showed an increased risk of all-cause dementia (risk ratio (RR) 1.30, 95% confidence interval (CI) 1.18–1.45), AD (RR 1.40, 95% CI 1.13–1.73) and VaD (RR 1.38, 95% CI 1.15–1.66). For all-cause dementia, the risk increased by 34% for every 20 cigarettes per day (RR 1.34, 95% CI 1.25–1.43). Former smokers did not show an increased risk of all-cause dementia (RR 1.01, 95% CI 0.96–1.06), AD (RR 1.04, 95% CI 0.96–1.13) and VaD (RR 0.97, 95% CI 0.83–1.13). Subgroup analyses indicated that (1) the significantly increased risk of AD from current smoking was seen only in apolipoprotein E ε4 noncarriers; (2) current smokers aged 65 to 75 years at baseline showed increased risk of all-cause dementia and AD compared to those aged over 75 or under 65 years; and (3) sex, race, study location and diagnostic criteria difference in risk of dementia was not found.ConclusionsSmokers show an increased risk of dementia, and smoking cessation decreases the risk to that of never smokers. The increased risk of AD from smoking is more pronounced in apolipoprotein E ε4 noncarriers. Survival bias and competing risk reduce the risk of dementia from smoking at extreme age.