The Association between Smoking and Alzheimer's Risk

Some studies have suggested a protective effect of smoking on Alzheimer's. Meta-analyses of case-control and cohort studies to investigate the risk of Alzheimer's associated with smoking found that these studies produce conflicting results as to the association between smoking and Alzheimer's.

The two following studies provide evidence of the risk of Alzheimer’s associated with smoking.

The Rotterdam study was a population-based follow-up study of 6870 elderly people aged 55 years and older who were initially free of dementia. Smoking history was taken at baseline and participants were classified as never smokers, former smokers, and current smokers.

During mean follow-up of 2.1 years, 146 incident cases of dementia were detected, of which 105 were Alzheimer's. Compared with never smokers, smokers had an increased risk of dementia and Alzheimer's. Smoking was a strong risk factor for Alzheimer's in individuals without the APOE4 gene, but had no effect in participants with this gene.

It was concluded that smoking was associated with a doubling of the risk of dementia and Alzheimer's. The finding that carriers of the APOE4 gene had no increased risk of dementia suggests an interaction between smoking and the APOE4 gene in the cause of Alzheimer's.

In the Honolulu-Asia Aging Study, the association between mid-life smoking and late-life dementia was studied in 3734 Japanese-American men. The risk of Alzheimer's in smokers increased with medium and heavy smoking levels. Very heavy smoking was not associated with Alzheimer's.

In an autopsied subsample, the number of neuritic plaques increased with amount smoked. This study suggests that amount smoked is associated with an increasing risk of Alzheimer's and Alzheimer-type neuropathology up to heavy smoking levels. The lack of association in very heavy smokers may be due to a hardy survivor effect.

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References:
1. Tyas SL, White LR, Petrovitch H, Webster Ross G, Foley DJ, Heimovitz HK, Launer LJ. Mid-life smoking and late-life dementia: the Honolulu-Asia Aging Study. Neurobiol Aging. 2003 Jul-Aug;24(4):589-96. PMID: 12714116.
2. Ott A, Slooter AJ, Hofman A, van Harskamp F, Witteman JC, Van Broeckhoven C, van Duijn CM, Breteler MM. Smoking and risk of dementia and Alzheimer's disease in a population-based cohort study: the Rotterdam Study. Lancet. 1998 Jun 20;351(9119):1840-3. PMID: 9652667.
3. Almeida OP, Hulse GK, Lawrence D, Flicker L. Smoking as a risk factor for Alzheimer's disease: contrasting evidence from a systematic review of case-control and cohort studies. Addiction. 2002 Jan;97(1):15-28. PMID: 11895267.
4. Image by Patrick J. Lynch, medical illustrator; C. Carl Jaffe, MD, cardiologist.