Relation between smoking and risk of dementia and Alzheimer disease: the Rotterdam Study
Reitz C, den Heijer T, van Duijn C, Hofman A, Breteler MM;
Commented by , 8 Oct 2007
Aim of the study
To assess if smoking habits and pack-years of smoking are associated with the risk of dementia, Alzheimer's disease (AD), and vascular dementia (VaD).
Prospective population-based cohort study of 6,868 participants from Ommoord, a district of the city of Rotterdam, 55 or older and free of dementia at baseline between 1990 and 1993, with follow-up in 1993-4, 1997-9, 2002-4.
Diagnosis of dementia and its cause was done with standard research criteria (NINCDS-ADRDA for AD, NINDS-AIREN for VaD). Participants were questioned about current and past smoking habits. Cox proportional hazard models were used to relate smoking status at baseline with the risk of incident dementia, AD and VaD using "never smokers" as the reference category in all analysis, which were repeated stratifying by apoE4 genotype, gender and median of age.
After a mean follow-up of 7.1 years, 706 persons (10.3%) had dementia, 555 (78.6%) caused by AD and 79 (11.2%) caused by VaD. 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 was restricted to persons without the apoE4 allele. There was no association between current smoking and VaD, and between past smoking and risk of dementia, AD or VaD.
Professor Gauthier's comments
There has been some debate in the epidemiological literature as to the potential protective effects of smoking on incident dementia, which was suggested in older case-control studies. Recent prospective cohort studies reported an increased or unchanged risk.
The current study shows that current smoking increases the risk of dementia in at least 85% of the population (15% of Caucasians have one or two apoE4 allele). In Japanese American men where there is very little apoE4 allele, a similar increased risk has been found (ref. 1).
The authors did not find evidence that a higher mortality in apoE4 carriers was an explanation for the differences in risk for dementia. They propose that current smoking cause augmentation of cholinergic metabolism by upregulation of choline nicotinic receptors in the brain, increase oxidative stress and lower intake of antioxidants.
1. Tyas SL, White LR, Petrovitch H, Webster Ross G, Foley DJ, et al. Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiology of Aging 2003; 24 (4);589-596