American Journal of Epidemiology Vol. 146, No. 5: 373-384
Copyright © 1997 by The Johns Hopkins University School of Hygiene and Public Health
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Head Injury and Risk of Alzheimer's Disease by Apolipoprotein E Genotype
1Department of Epidemiology, School of Public Health and Community Medicine, University of Washington Seattle, WA
2Department of Biostatistics, School of Public Health and Community Medicine, University of Washington Seattle, WA
3Department of Neurology, School of Medicine, University of Washington Seattle, WA
4Department of Medicine, School of Medicine, University of Washington Seattle, WA
5Department of Psychiatry and Behavioral Sciences, School of Medicine, University of Washington Seattle, WA
6Department of Pharmocology, School of Medicine, University of Washington Seattle, WA
7Geriatric Research, Education, and Clinical Center, Veterans Affairs Medical Center Seattle, WA
Reprint requests to Dr. Walter A. Kukull, Box 357236, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195
Head injury and apolipoprotein E (APOE)-epsilon 4 (e4) genotype have each been associated with increased risk of Alzheimer's disease. If APOE-e4 affects neuronal viability and branching, and if response to head injury differs in e4 patients, then the association between head injury and Alzheimer's disease may vary with the presence of the e4 allele. The authors examined this association in a case-control study conducted between 1987 and 1995 among enrollees of the Group Health Cooperative of Puget Sound, a health maintenance organization in Seattle, Washington. Proxy informants reported prior head injury with loss of consciousness for 32 of 349 patients with probable Alzheimer's disease and for 16 of 342 control subjects of similar age and sex who had been randomly selected from the same population (odds ratio (OR) = 2.1, 95% confidence interval (CI) 1.1–3.8). Elevated risk was observed among men (OR = 4.2, 95% CI 1.5–11.5) but not among women (OR = 1.1, 95% CI 0.5=2.6). No significant variation in the head injury-Alzheimer's disease risk relation by APOE-e4 genotype was found among 230 cases and 309 controls (OR = 3.1 (95% CI 0.7–14.6) for persons with at least one e4 allele and OR = 2.0 (95% CI 0.8–5.2) for those without e4). Neither age, education, race, type of proxy informant, nor duration of relationship with the proxy confounded the association. Head injury with loss of consciousness, although uncommon in this sample, was associated with increased risk of Alzheimer's disease. APOE-e4 was an independent risk factor which neither modified nor confounded the association. Susceptibility to Alzheimer's disease as conferred by APOE-e4 does not appear to increase the risk associated with head injury. Am J Epidemiol 1997;146:373–84.
Alzheimer's disease; apolipoproteins E; dementia; head injuries; genotype
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