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

Abstract

Aims: To assess associations that endogenous estradiol and testosterone levels have with cognitive function in older adults with Type 2 diabetes mellitus (T2DM).

Methods: We use data from the Look AHEAD clinical trial of behavioral weight loss. Endogenous estradiol and total testosterone levels were determined using stored serum from 996 individuals, mean age 69 years, at two times (averaging 4 years apart) during years 8-18 of follow-up. One to four standardized assessments of attention, executive function, memory, and verbal fluency were collected during this follow-up. Mixed effects models and multiple imputation were used to assess associations that estradiol and total testosterone levels had with body mass index and cognitive function.

Results: Estradiol levels were not associated with cognitive function in either sex. Total testosterone levels were not associated with cognitive function in women, but greater total testosterone levels were associated with better verbal fluency in men (p < 0.001), most strongly among those carrying the APOE-e4 allele (interaction p = 0.02). The weight loss intervention left a legacy of relatively lower cognitive functioning among women, which was not mediated by current levels of sex hormones.

Conclusions: Behavioral weight loss intervention does not affect cognitive functioning through mechanisms related to estradiol or testosterone.

Clinicaltrials: gov Identifier: NCT00017953.

Keywords: Obesity; Sex differences; Sex hormones; Weight loss.

Fig. 1.

Mean difference in standardized cognitive function z-scores between intervention groups (Intensive Lifestyle Intervention minus Diabetes Support and Education) across Epoch 1 and Epoch 2 by gender after adjustment for covariates education, race/ethnicity, current age, current HbA1c, and current body mass index: without and with additional adjustment for estradiol and total testosterone.