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Scott D. Moffat, PhD; Alan B. Zonderman, PhD; S. Mitchell Harman, MD; Marc R. Blackman, MD; Claudia Kawas, MD; Susan M. Resnick, PhD

Arch Intern Med. 2000;160:2193-2198.

Background  The observation that dehydroepiandrosterone (DHEA) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition. In the United States, DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes.

Objective  To investigate the relationship between age-associated decreases in endogenous DHEA sulfate (DHEA-S) concentrations and declines in neuropsychological performance in a prospective, longitudinal study.

Methods  The subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging. The men were aged 22 to 91 years at the initial visit, and they were followed up for as long as 31 years (mean, 11.55 years), with biennial reassessments of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations. Outcome measures were the results of cognitive tests of verbal and visual memory, 2 tests of mental status, phonemic and semantic word fluency tests, and measures of visuomotor scanning and attention. Serum DHEA-S concentrations were determined by standard radioimmunoassay.

Results  Neither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline. A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences, despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years.

Conclusion  Our longitudinal results augment those of previous prospective studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men.

From the Laboratories of Personality and Cognition (Drs Moffat, Zonderman, and Resnick) and Clinical Investigation (Dr Harman), Intramural Research Program, National Institute on Aging, and the Departments of Medicine (Dr Blackman) and Neurology (Dr Kawas), Johns Hopkins University School of Medicine, Baltimore, Md.

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