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LETTER TO THE EDITOR |
Wayne State University Detroit, Michigan
Address correspondence to Scott D. Moffat, PhD, Institute of Gerontology, Wayne State University, 87 E. Ferry, 226 Knapp Bldg., Detroit, MI, 48202. E-mail: moffat{at}wayne.edu
To the Editor:
In their article, "Age, Hormones, and Cognitive Function Among Middle Aged and Elderly Men: Cross Sectional Evidence from the Massachusetts Male Aging Study," Fonda and colleagues present new data on the association between testosterone (and other hormones) and cognitive function in a sample of older men, reporting a null finding after incorporating appropriate covariates. This study makes a novel and important contribution to the growing literature investigating the possible effects of androgens on cognitive function in elderly men. However, the authors have reached conclusions that go beyond those justified either by their own data or by a complete review of the extant literature. In particular, the authors conclude that "hormones do not mediate the age-cognition relationship" and that "it is necessary to look for other explanatory pathways." This conclusion is premature given the current state of the literature. As the authors note, several epidemiological studies exist that have found positive associations between androgens and cognitive function in elderly men [see, e.g., (1–3)]. The authors further note that longitudinal data on this topic is lacking. Our own longitudinal data from the Baltimore Longitudinal Study of Aging speak directly to this issue. We investigated age-associated decreases in endogenous testosterone concentrations and declines in neuropsychological performance among 407 men aged 50 to 91 years. The men in the study were followed longitudinally for an average of 10 years, with assessments of multiple cognitive domains and contemporaneous determination of serum total testosterone, sex hormone-binding globulin and a calculated free testosterone index. In this study, higher free testosterone was associated with higher scores on visual and verbal memory and visuospatial functioning and with a reduced rate of decline in visual memory. These findings were robust with respect to the inclusion of numerous covariates in our statistical models (3). Although a longitudinal design affords great advantages over a cross-sectional model, it nevertheless does not establish a causal relation between testosterone and cognitive decline. Large, well-controlled intervention studies will be necessary to reach a more definitive conclusion.
In regard to intervention studies, Fonda and colleagues conclude that "exogenously administered hormones are apparently not the solution for reducing [cognitive] decline." In support of this statement, they cite three negative findings from small placebo controlled intervention studies. However, the authors omit numerous published positive findings. Well-designed placebo controlled studies have demonstrated that testosterone may enhance spatial cognition, spatial memory, working memory, and possibly verbal memory (4–8). These studies are small and present findings that are less than conclusive, but at a minimum, their existence suggests a more nuanced evaluation of the literature than the conclusions of Fonda and colleagues would imply. Indeed, the Institute of Medicine of the National Academy of Sciences recently recommended that clinical trials be conducted in men aged 65 years and older with testosterone concentrations below the physiologic levels of young adult men. The report specifically identified cognitive function as one of four target areas in need of clinical investigation. Testosterone intervention to prevent or ameliorate cognitive decline should not be advocated unless, and until, research clearly bears out both the efficacy and safety of so doing. However, a complete review of the extant literature leads to the conclusion that this is an active area of inquiry and a subject of ongoing debate.
F
Decision Editor: Luigi Ferrucci, MD, PhD
Received July 7, 2005
Accepted July 24, 2005
References
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