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Objectives: It has been suggested in some studies that head injury is a risk factor for AD, and that this risk is heightened among carriers of the APOE-ε4 allele. We examined the effects of head injury and APOE genotype on AD risk in a large family study.

Subjects: A total of 2,233 probands who met criteria for probable or definite AD and their 14,668 first-degree family members (4,465 parents, 7,694 siblings, and 2,509 spouses) were ascertained at 13 centers in the United States, Canada, and Germany participating in the MIRAGE (Multi-Institutional Research in Alzheimer Genetic Epidemiology) project. Information on head injury was collected by interview of multiple informants and review of medical records. Nondemented relatives and spouses served as control subjects for this study.

Methods: Odds of AD for head trauma with or without loss of consciousness were computed by comparing probands with …