Relation between smoking and risk of dementia and Alzheimer disease
The Rotterdam Study

NEUROLOGY 2007;69:998-1005
C. Reitz, MD, PhD, T. den Heijer, MD, PhD, C. van Duijn, PhD, A. Hofman, MD, PhD and M.M.B. Breteler, MD, PhD
From the Departments of Epidemiology & Biostatistics (C.R., T.d.H., C.v.D., A.H., M.M.B.B.) and Neurology (T.d.H.), Erasmus Medical Center, Rotterdam, The Netherlands.
Address correspondence and reprint requests to DrB. Breteler, Department of Epidemiology & Biostatistics, Erasmus Medical Center, PO Box 1738, 3000DR Rotterdam, The Netherlands

Background and Objective: Previous studies relating smoking with the risk of dementia have been inconsistent and limited in their validity by short follow-up times, large intervals between baseline and follow-up assessments, and unspecific determination of dementia diagnosis. We re-assessed after longer follow-up time in the large population-based cohort of the Rotterdam Study whether smoking habits and pack-years of smoking are associated with the risk of dementia, Alzheimer disease (AD), and vascular dementia (VaD).

Methods: Prospective population-based cohort study in 6,868 participants, 55 years or older and free of dementia at baseline. First, Cox proportional hazard models were used to relate smoking status at baseline with the risks of incident dementia, VaD, and AD, using never smokers as the reference category in all analyses. Then Cox proportional hazard models were used to relate pack-years of smoking with the risks of incident dementia, VaD, and AD. To explore the impact of the APOE{varepsilon}4 allele, sex, and age on the association between smoking status and dementia, we repeated all analyses stratifying, in separate models, by APOE{varepsilon}4 genotype, sex, and median of age.

Results: After a mean follow-up time of 7.1 years, current smoking at baseline was associated with an increased risk of dementia (HR 1.47, 95% CI 1.18 to 1.86) and AD (HR 1.56, 95% CI 1.21 to 2.02). This increase in disease risk was restricted to persons without the APOE{varepsilon}4 allele. There was no association between current smoking and risk of VaD, and there was no association between past smoking and risk of dementia, AD, or VaD.

Conclusion: Current smoking increases the risk of dementia. This effect is more pronounced in persons without the APOE{varepsilon}4 allele than APOE{varepsilon}4 carriers




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