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OBJECTIVES: To clarify the association between midlife and late-life smoking and risk of dementia. DESIGN: Prospective cohort study. SETTING: The Hisayama Study, Japan. PARTICIPANTS: Japanese community-dwellers without dementia aged 65 to 84 (mean age 72) followed for 17 years (1988-2005) (N = 754), 619 of whom had participated in a health examination conducted in 1973-74 (mean age, 57) and were included in the midlife analysis. MEASUREMENTS: The risk estimates of smoking status on the development of dementia were computed using a Cox proportional hazards model. RESULTS: During follow-up, 252 subjects developed all-cause dementia; 143 had Alzheimer's disease (AD), and 76 had vascular dementia (VaD). In late life, the multi-variable-adjusted risk of all-cause dementia was significantly greater in current smokers than in never smokers; similar associations were seen for all-cause dementia, AD, and VaD in midlife current smokers. Meanwhile, no significant association was observed between past smoking and risk of any type of dementia in late or midlife. Multivariable analysis showed that smokers in midlife and late life had significantly greater risks than lifelong nonsmokers of all-cause dementia (adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI) = 1.49-3.49), AD (aHR = 1.98, 95% CI = 1.09-3.61), and VaD (aHR = 2.88, 95% CI = 1.34-6.20). Such associations were not observed for midlife smokers who quit smoking in late life. CONCLUSION: Persistent smoking from mid- to late life is a significant risk factor for dementia and its subtypes in the general Japanese population. [ABSTRACT FROM AUTHOR]