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1 Harvard Medical School, Joslin Diabetes Center, Boston, Massachusetts.
2 Department of Epidemiology and Biostatistics, School of Public Health, Boston University Medical College, Massachusetts.
3 New England Research Institutes, Watertown, Massachusetts.
4 Department of Medicine, University of Massachusetts Medical Center, Worcester.
Address correspondence to: Dr. John B. McKinlay, New England Research Institutes, 9 Galen Street, Watertown, MA 02472 (E-mail: JohnM{at}neri.org) or Dr. Stephanie J. Fonda, Joslin Diabetes Center, One Joslin Place, Boston, MA 02215 (E-mail: stephanie.fonda{at}joslin.harvard.edu)
Background. This study examines interrelationships among age, hormones, and cognition for middle-aged and elderly men, and tests whether hormones predict lower cognitive functioning and mediate the age–cognition relationship.
Methods. We analyzed Time 2 data from the Massachusetts Male Aging Study, a population-based cohort study. Selection criteria included complete information on cognition and hormones (n = 981). Cognitive measures included working memory (Backward Digit Span test), speed/attention (Digit Symbol Substitution test), and spatial ability (Figural Relations test). Hormones included free testosterone, total testosterone, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), androstanediol glucuronide (3 
-A-diol-gluc), luteinizing hormone (LH), follicle-stimulating hormone (FSH), sex hormone-binding globulin (alternatively known as a "binding protein") (SHBG), prolactin (PRL), estrone (E1), and cortisol (CRT). Age was measured in years. Adjusted analyses added educational attainment, health conditions and behaviors, body mass index, and depression.
Results. Older age was associated with lower cognitive functioning. In unadjusted models, logged free and total testosterone, DHEA, and DHEAS related to higher functioning in at least one cognitive domain; logged FSH, SHBG, and LH related to lower functioning in at least one cognitive domain; and logged E1, CRT, and PRL were not significant. In adjusted models, logged hormones did not relate to cognitive function except for logged E1and CRT, which had negative effects. Logged hormones did not mediate the age–cognition relationship.
Conclusions. The direct effects of hormones on cognition are not significant when salient factors are considered. Further, hormones do not mediate the age–cognition relationship; it is necessary to look to other explanatory pathways.
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