Relationship Between Testosterone and Cognitive Function in Elderly Men with Dementia

To the Editor: A decrease in sex hormones with aging has been reported to be related to psychosomatic disorders such as late-onset hypogonadism syndrome, frailty, and cognitive impairment in adult men. For example, a community-based cross-sectional study has shown that elderly men with a lower blood concentration of bioavailable testosterone have more-severe impairment of cognitive function. Moreover, a longitudinal study indicated that serum free testosterone (FT) concentration could predict memory performance and cognitive status in elderly men, but it is unknown whether lower testosterone concentration is related to cognitive impairment in individuals with dementia, because the previous studies primarily focused on a healthy community-based population. Also, few studies have addressed the relationship between testosterone and cognitive function in elderly Japanese men. One recent cross-sectional study showed that total testosterone and FT concentration were associated with activities of daily living (ADLs) in institutionalized elderly men. This study also revealed that a relationship between testosterone and cognitive function could be found even in institutionalized elderly men with physical or neuropsychiatric dysfunction. Thus, whether lower testosterone concentration is related to deterioration of ADL in elderly men with cognitive impairment was longitudinally investigated. Fifty-two male outpatients attending the Center for Comprehensive Care on Memory Disorders at Kyorin University Hospital were recruited (mean age 77.0 ± 5.5, range 65–87). Participants’ clinical backgrounds were hypertension, 48.9%; diabetes mellitus, 12.2%; and dyslipidemia, 38.1%. None had a history of stroke. Comprehensive geriatric assessment was performed based on basic ADLs (Barthel Index), instrumental ADLs (Lawton and Brody IADLs, 0–5 points in men), cognitive function (Mini-Mental State Examination (MMSE)), mood (Geriatric Depression Scale (GDS), 15 items), and vitality (Vitality Index, 10-point scale). This assessment was repeated 1, 2, and 3 years after baseline assessment at the first visit to the clinic. At the first visit, blood was drawn after an overnight fast and FT concentration was measured using radioimmunoassay. FT values ranged from 1.0 to 53.0 pmol/L (mean ± SD 30.4 ± 11.0 pmol/L). Participants were classified into three groups according to tertile according to the baseline FT value (Figure 1), and the parameters from the comprehensive geriatric assessment were compared between groups and visits. Statistical data were analyzed using SPSS version 17.0 (SPSS, Inc., Chicago, IL). One-way analysis of variance (ANOVA) was applied for comparisons between groups, and the Fisher post hoc test was applied when significant (P < .05). Oneway repeated ANOVA was used for comparisons between baseline and the 1-, 2-, and 3-year visits, and the Fisher post hoc test was applied when significant (P < .05). There were no significant differences between groups in age (high, 75.3; middle, 76.6; low, 79.0), basic ADLs (high, 96.9; middle, 99.1; low, 95.3 points), MMSE (high, 23.2; middle, 25.1; low, 23.1 points), GDS-15 (high, 5.1; middle, 4.1; low, 4.6 points), and Vitality Index (high, 9.1; middle, 9.1; low, 8.8 points) at baseline, whereas IADLs tended to be lower (high, 4.1; middle, 4.1; low, 3.4 points, P = .06) in the low FT tertile group than in the other groups. At the 1-year visit, there was no difference in change in MMSE score from baseline between the groups, although the decrease in MMSE score was larger in the low FT tertile group than in the middle and high tertile groups at the 2and 3-year visits (Figure 1). Also, MMSE scores were lower in the low FT tertile group at the 2(P = .009) and 3-year (P < 0.001) visits than at baseline, whereas they were not lower in the middle and high tertile groups. In contrast, there was no such trend in basic ADLs, IADLs, GDS scores, and Vitality Index. Multiple regression analysis was performed with a decrease in MMSE score as a dependent variable and age; ADLs; body mass index; presence of hypertension, diabetes mellitus, or hyperlipidemia; and FT concentration as independent variables to consider factors affecting cognitive impairment, according to a previous report. Blood FT concentration was found to be an independent predictor of decrease in MMSE score at the 3-year visit (b = 0.492, P = .02). A number of investigations support the biological plausibility of a protective effect of testosterone against cognitive dysfunction. The present findings from memory clinic outpatients are consistent with previous findings observed in elderly community-based men, showing a relationship between FT concentration and cognitive performance. Furthermore, the present findings indicate that a lower FT concentration could lead to a faster decline in cognitive function in elderly Japanese men who already show cognitive impairment. This study provides fundamental data for the future study of hormone replacement therapy for cognitive decline in elderly adults with low FT.