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From the Department of Psychiatry and Behavioral Sciences (Drs. Plassman, Steffens, Welsh–Bohmer, and Breitner, and M.J. Helms, T.N. Newman, D. Drosdick, and B.A. Gau), the Joseph and Kathleen Bryan Alzheimer’s Disease Research Center (Drs. Welsh–Bohmer and Burke), and the Department of Neurology (Dr. Burke), Duke University Medical Center, Durham, NC; the Epidemiology, Demography, and Biometry Program of the National Institute on Aging (Drs. Havlik and Guralnik, and C. Phillips), Bethesda, MD; and the School of Hygiene and Public Health (Dr. Breitner), Johns Hopkins University, Baltimore, MD.
Address correspondence and reprint requests to Dr. Brenda L. Plassman, Box 41, 905 W. Main Street, Suite 25D, Durham, NC 27701; e-mail: brenda.plassman{at}duke.edu
BACKGROUND: The association between antecedent head injury and AD is inconsistent.
OBJECTIVE: To examine the association between early adult head injury, as documented by military hospital records, and dementia in late life; and to evaluate the interaction between head injury and APOE 
4 as risk factors for dementia.
METHODS: The study had a population-based prospective historical cohort design. It included men who were World War II Navy and Marine veterans, and were hospitalized during their military service with a diagnosis of either a nonpenetrating head injury or another unrelated condition. In 1996 to 1997, military medical records were abstracted to document the occurrence and details of closed head injury. The entire sample was then evaluated for dementia and AD using a multistage procedure. There were 548 veterans with head injury and 1228 without head injury who completed all assigned stages of the study. The authors estimated risk of dementia, specifically AD, using proportional hazards models.
RESULTS: Both moderate head injury (hazard ratio [HR] = 2.32; CI = 1.04 to 5.17) and severe head injury (HR = 4.51; CI = 1.77 to 11.47) were associated with increased risk of AD. Results were similar for dementia in general. The results for mild head injury were inconclusive. When the authors stratified by the number of APOE 4 alleles, they observed a nonsignificant trend toward a stronger association between AD and head injury in men with more 4 alleles.
CONCLUSIONS: Moderate and severe head injuries in young men may be associated with increased risk of AD and other dementias in late life. However, the authors cannot exclude the possibility that other unmeasured factors may be influencing this association.
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