Association of serum dehydroepiandrosterone sulfate and cognition in older adults: Sex steroid, inflammatory, and metabolic mechanisms.

Abstract

Dehydroepiandrosterone sulfate (DHEAS) levels and cognitive function decline with age, and a role for DHEAS in supporting cognition has been proposed. Higher DHEAS levels may be associated with better cognitive performance, although potential mechanisms for this relationship are not well established. We performed a cross-sectional study of the relationship between serum DHEAS and three aspects of cognition--executive function, working memory, and processing speed--in 49 men and 54 women, aged 60-88 years, with low serum DHEAS levels. We examined three potential mechanisms of DHEAS action--sex hormone sufficiency, inflammatory status, and glucose regulation. After adjustment for multiple covariates, higher serum DHEAS levels were associated with better working memory (standardized beta coefficient 0.50, p < .05), with a trend toward better executive function (standardized beta coefficient 0.37, p < .10) in men only. There was a nonsignificant trend toward a negative association between levels of tumor necrosis factor α (TNFα) and working memory in the combined population (standardized beta coefficient -0.22, p < .10). None of the glucoregulatory measures was associated with cognitive function. The relationship between DHEAS and cognition is complex and differs by sex and cognitive domain. This study supports the need for further investigations of the sex-specific effects of DHEAS on cognition and its underlying mechanisms of action.