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From the Laboratory of Personality and Cognition (Drs. Moffat, Zonderman, and Resnick) and Laboratory of Clinical Investigation (Dr. Metter), National Institute on Aging, Intramural Research Program, Baltimore, MD; Institute of Gerontology and Department of Psychology (Dr. Moffat), Wayne State University, Detroit, MI; Department of Neurology (Dr. Kawas), University of California, Irvine, CA; Laboratory of Clinical Investigation (Dr. Blackman), National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD; and Kronos Longevity Research Institute (Dr. Harman), Phoenix, AZ.
Address correspondence and reprint requests to Dr. Susan M. Resnick, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore, MD 21224; e-mail: resnick{at}lpc.grc.nia.nih.gov
Objective: To investigate the relationships between age-associated decreases in endogenous serum total testosterone (T) and a free T index (FTI) in men and the subsequent development of Alzheimer disease (AD).
Method: The authors used a prospective, longitudinal design with follow-up in men since 1958. Participants were from the Baltimore Longitudinal Study of Aging, a community-dwelling volunteer sample with baseline ages of 32 to 87 years. All subjects were free of AD at baseline T assessment. Five hundred seventy-four men assessed at multiple time points were followed for a mean of 19.1 years (range, 4 to 37 years). Diagnoses of AD were based on biennial physical, neurologic, and neuropsychological evaluations.
Results: Diagnosis of AD was associated inversely with FTI by itself and after adjustments for age, education, smoking status, body mass index, diabetes, any cancer diagnoses, and hormone supplements. In separate analyses, total T and sex hormone binding globulin were not significant predictors after adjustment with covariates. Increases in the FTI were associated with decreased risk of AD (hazard ratio = 0.74; 95% CI = 0.57 to 0.96), a 26% decrease for each 10-nmol/nmol FTI increase.
Conclusions: Calculated free testosterone concentrations were lower in men who developed Alzheimer disease, and this difference occurred before diagnosis. Future research may determine whether higher endogenous free testosterone levels offer protection against a diagnosis of Alzheimer disease in older men.
Received May 13, 2003. Accepted in final form November 24, 2003.
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