Associations between cognitive function and endogenous levels of estradiol and testosterone in adults with Type 2 diabetes?

Abstract

AbstractBackgroundType 2 diabetes mellitus (T2D) accelerates cognitive decline in women and men. Among older women, prior reports suggest that higher endogenous estradiol levels may further accelerate the cognitive decline associated with T2D and increase risks for cognitive impairment. Testosterone may interact directly with cognitive decline in T2D, or through its conversion to estradiol via the aromatase enzyme.MethodsEstradiol (E2) and total testosterone (TT) concentrations were determined using stored serum from 996 individuals, mean (±SD) age 69±6 and not receiving hormone therapies, collected at two times (averaging 4 years apart). Serum was collected during follow‐up years 8‐18 of the Look AHEAD cohort, a randomized controlled clinical trial of a 10‐year behavioral weight loss intervention in individuals with T2D and overweight or obesity at trial enrollment. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during follow‐up years 8‐18. Mixed effects models were used to assess associations that E2 and TT concentrations had with current body mass index (BMI) and cognitive function.ResultsGreater current BMI was associated with higher E2 concentrations in women and men, and greater TT concentrations in women, but lower TT concentrations in men (all p<0.001). The weight loss intervention did not leave a legacy of differences in E2 and TT concentrations. E2 concentrations were not associated with cognitive function in women or men. TT concentrations were not associated with cognitive function in women, but greater TT concentrations were associated with better verbal fluency in men (p<0.001), most strongly among those carrying the APOE‐e4 allele (interaction p = 0.02). While the weight loss intervention left a legacy of relatively lower cognitive functioning among women, this was not mediated by current concentrations of E2 and TT.ConclusionsContrary to prior reports, we found no evidence that higher endogenous E2 concentrations were related to worse cognitive functioning in women with T2D. Higher TT concentrations were associated with better verbal fluency in men, but not women. The legacy of modestly lower cognitive function in women left by a 10‐year weight loss intervention was unrelated to any long‐term alterations in E2 or TT concentrations.