Depressive Symptoms Longitudinally Mediate the Effect of Hyperglycemia on Memory Decline in Type 2 Diabetes

OBJECTIVE: We sought to examine the mediating role of changes in depressive symptoms in the association between chronic hyperglycemia and longitudinal cognition in a sample of older adults with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted a longitudinal mediation analysis using structural equation modeling of observational data collected over six years from 2155 participants with T2D (ages 51+) in the U.S.-wide Health and Retirement Study. T2D was defined using self-reported diagnosis, and HbA1c was assessed at study baseline. Self-reported depressive symptoms were assessed at two time points, four years apart. Episodic memory was measured using a list-learning test administered at three time points over six years. We adjusted for socio-demographics, chronic health comorbidities, medication adherence, study enrollment year, and prior years’ depressive symptoms and memory scores.

RESULTS: At baseline, mean age was 69.4 ± 9.1, mean HbA1c was 7.2% ± 1.4%, 55.0% were women, 19.3% were non-Latinx Black, and 14.0% were Latinx. Higher baseline levels of HbA1c were associated with increases in depressive symptoms over four years, which in turn, were associated with lower memory two years later. Depressive symptoms accounted for 19% of the longitudinal effect of HbA1c on memory over the six-year period. Sensitivity analyses ruled out alternative directions of associations.

CONCLUSIONS: Incident elevations in depressive symptoms mediated the longitudinal association between hyperglycemia and six-year episodic memory scores. For older adults with T2D, interventions to prevent HbA1c-related incident depressive symptoms may be beneficial in reducing the neurotoxic effects of chronic hyperglycemia on cognition.