Interactions between estradiol, diabetes, and brain aging and the risk for cognitive impairment.

The Women's Health Initiative Memory Study reported that older women using conjugated equine estrogens hormone therapy (HT) with or without medroxyprogesterone acetate were at increased risk for probable dementia and smaller brain volumes. These adverse effects were greatest among women who had type 2 diabetes mellitus (T2DM) at baseline or who developed the disease during follow-up. This review summarizes existing literature from randomized trials, observational studies, and preclinical studies to provide a fundamental understanding of the effects of the interaction between T2DM and HT on cognitive and metabolic health changes in brain aging.

Effects of Type 2 Diabetes on Brain Structure and Cognitive Function: African American-Diabetes Heart Study MIND.

BACKGROUND AND PURPOSE: Rates of type 2 diabetes are higher among African Americans compared with individuals of European ancestry. The purpose of this investigation was to determine the relationship between MR imaging measures of brain structure (volume of GM, WM, WM lesions) and cognitive function in a population of African Americans with type 2 diabetes. These MR imaging measures of brain structure are affected by type 2 diabetes-associated macrovascular and microvascular disease and may be associated with performance on tasks of cognitive function in the understudied African American population. MATERIALS AND METHODS: African Americans with type 2 diabetes enrolled in the African American-Diabetes Heart Study MIND study (n = 263) were evaluated across a broad range of cognitive domains and imaged with brain MR imaging. Associations between cognitive parameters and MR imaging measures of whole-brain GM, WM, and WM lesion volumes were assessed by using adjusted multivariate models. RESULTS: Lower GM volume was associated with poorer performance on measures of general cognitive function, working memory, and executive function. Higher WM lesion volume was associated with poorer performance on a smaller subset of cognitive domains compared with GM volume but included aspects of working memory and executive function. There were no statistically significant associations with WM volume. CONCLUSIONS: Markers of cortical atrophy and WM lesion volume are associated with cognitive function in African Americans with type 2 diabetes. These associations are described in an African American cohort with disease control similar to that of individuals of European ancestry, rather than underserved African Americans with poor access to health care. Interventions to reduce cortical atrophy and WM disease may improve cognitive outcomes in this understudied population.