Low testosterone and the risk of dementia in elderly men: Impact of age and education

OBJECTIVE: The objective of this study was to examine the association of plasma estradiol and testosterone with risk for dementia in elderly men. METHODS: Within the population based Three-City study, including 3650 men age 65 years and older, a case-cohort design was set up after 4-years of follow-up. Baseline plasma levels of total 17-β estradiol (Total-E2), total testosterone (total-T) and bioavailable testosterone (bio-T) were measured for all cases of incident dementia (n=105) and for a random sample of the cohort (n=413). Cox regression models were used to estimate multivariate steroid sex hormone-associated hazard ratios (HR) and 95% confidence intervals of dementia. RESULTS: There was a reverse J-shaped relationship between total-T and risk for dementia (P=.007). Compared with the median tertile, the HRs associated with total-T in the lower and upper tertile were increased (HR, 2.33; P=.026; HR, 1.9, P=.126; respectively). Low bio-T was associated with a greater risk for dementia (HR for one standard deviation of decreasing log(bio-T), 1.29; 95% confidence interval, 1.03-1.62). An interaction was found between bio-T and age (P<.0001), and bio-T and education (P=.044). Risk for dementia associated with low bio-T was greater in older men (80 years or older) than in younger men (younger than 80 years; HR, 3.11; P=.011 vs. HR, 1.07, P=.715, respectively) and in men with high level of education compared with those with low level of education (HR, 2.32; P=.0002 vs. HR, 0.95; P=.790, respectively). No significant association was found between Total-E2 and dementia. CONCLUSIONS: Low levels of testosterone are associated with a risk for dementia in elderly men. The association between low bio-T and dementia may be more relevant to men 80 years or older and men with a high level of education.