Smoking and the Risk of Alzheimer's Disease in a Population-Based Cohort Study
ABSTRACT & COMMENTARY
Synopsis: Smoking was a strong risk factor for Alzheimer's disease in individuals without the apolipoprotein (APO[4] allele (4.6 [1.5-14.2]) but had no effect upon risk in participants with this allele.
Source: Ott A, et al. Lancet 1998;351:1840-1843.
Previous studies suggested that smoking protected against the development of Alzheimer's dementia, but these studies were case-control designs based on prevalence. Prospective studies were inconclusive. One study suggested that the neuroprotective effect of smoking was limited to those with the APO(4) allele. Therefore, Ott and colleagues designed a prospective, community-based, cohort study of individuals 55 years and older living in a suburb of Rotterdam and also performed genotype analysis. Ott et al note that smoking increases the risk of vascular disease and that vascular involvement is more important than previously thought in the pathogenesis of Alzheimer's disease. A total of 6870 persons were enrolled for a total of 14,761 person-years. The analysis adjusted for age, sex, education, alcohol, and genotype. One limitation was that the mean duration of follow-up was short at 2.1 years. Another limitation was the relative paucity of older men who had never smoked. Ott et al found a large increase in dementia with increasing age, with an incidence of 52 per 1000 person-years in the age range of 85 years and older vs. 0.9 in the age range of 55-64 years. There was dose-dependent increase in risk from smoking. The increased risk of all-cause dementia and Alzheimer's disease was limited, however, to those without the APO(4) allele. In women, the risk of dementia was increased in those who were current smokers but not in former smokers.
COMMENT BY SARAH L. BERGA, MD
It is estimated that about 30% of people aged 85 years and older have some form of dementia. Alzheimer's disease and vascular dementia account for more than 90% of all cases. The burden of this disorder falls disproportionately to women because of their longevity and because they are often the caregivers for older parents. The recent demonstration that postmenopausal estrogen use protects against the development of dementia and slows its rate of progression has prompted those physicians who care for older women to familiarize themselves with the pathogenesis of dementia. It is important when counseling patients about the neuroprotective benefits of postmenopausal hormone use to also advise against habits that increase the risk of dementia. The importance of this study is that the data argue against the prevailing wisdom that smoking decreases the risk of dementia. The presence in a patient with dementia of one or more (4) alleles of the gene for apolipoprotein E has consistently been associated with Alzheimer's disease (Mayeux R, et al. N Engl J Med 1998;338:506-511). While the risk of dementia from smoking is greatest in those without the apolipoprotein E genotype, even in those with this genotype, smoking confers no protective effects. Patients wishing to avoid dementia should be informed of the deleterious effects of smoking and the protective effects of postmenopausal estrogen use. It remains to be determined if other therapies, such as aspirin and vitamin E use, should be universally recommended (Medical News and Perspectives. JAMA 1996;275:1389).
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