Accelerated brain aging in individuals with diabetes: Association with poor glycemic control and increased all-cause mortality

Background: Diabetes has been linked to accelerated brain aging, i.e., neuroimaging-predicted age of brain is higher than chronological age. This report evaluated whether accelerated brain aging in diabetes is associated with higher levels of glycated hemoglobin (HbA1c) and increased mortality. Methods: Brain age in Dallas Heart Study (n = 1949) was estimated using T1-weighted magnetic resonance imaging (MRI) scans and a previously-published Gaussian Processes Regression model. Accelerated brain aging (adjusted Δ brain age) was computed as follows: (brain age adjusted for chronological age)-minus-(chronological age). Mortality data until 12/31/2016 were obtained from the National Death Index. Associations of adjusted Δ brain age with diabetes in full sample and with HbA1c in individuals with diabetes were evaluated. Proportion of association between diabetes and all-cause mortality that was accounted for by adjusted Δ brain age were evaluated with mediation analyses. Covariates included Framingham 10-year risk score, race/ethnicity, income, body mass index, and history of myocardial infarction. Results: Diabetes was associated with] higher adjusted Δ brain age [estimate= 1.79; 95% confidence interval (CI): 0.889, 2.68]. Among those with diabetes, higher HbA1c (log-base-2-transformed) was associated with higher adjusted Δ brain age (estimate=3.88; 95% CI: 1.47, 6.30). Over a median follow-up of 97.5 months, 24/246 (9.8%) with diabetes and 63/1703 (3.7%) without diabetes died. Adjusted Δ brain age accounted for 65.3 (95% CI: 39.3, 100.0)% of the association between diabetes and all-cause mortality. Conclusion: Accelerated brain aging may be related to poor glycemic control in diabetes and partly account for the association between diabetes and all-cause mortality.