Sex hormones and incident dementia in older men: the health in men study

Background: Low circulating testosterone has been associated with dementia in older men but existing evidence from prospective studies is inconsistent. Methods: We conducted a prospective longitudinal study of 4069 community-dwelling older men free of dementia aged 71-88 years at baseline. The main objective of the study was to determine if men with low circulating sex hormones were more likely to develop dementia over time. The main biochemical exposures of interest were collected at baseline between 2001 and 2004 and men were assessed for incident dementia via an electronic health records database to the 31 st of December 2013. Results: Dementia developed in 499 men over a median of 10.5 years (range 9.4-12.2 years). The risk of developing dementia increased with decreasing total (hazard ratio [Hit] 1.14, 95% confidence interval [95%CI] 1.03-1.26 per standard deviation decrease) and calculated free testosterone (HR 1.18, 95%CI 1.06-1.31 per standard deviation decrease) after adjustment for age, baseline cognitive function, depression, body mass, hypertension, cardiovascular disease and total plasma homocysteine. Men in the lowest quartiles of total (adjusted HR L39, 95%CI 1.04-1.85) and calculated free testosterone (adjusted HR 1.43, 95%CI 1.08-1.90) had increased risk of developing dementia compared to those in the highest quartiles. Conclusions: Lower plasma total and calculated free testosterone were associated with increased risk of developing dementia independent of relevant measured clinical and biochemical factors and was not explained due to differential mortality in those with lower testosterone levels. The association between low testosterone and dementia is biologically plausible but data on the role of testosterone treatment in preventing dementia is lacking and adequately powered trials in men at risk would be welcome