Poor glycemic control is a well-established risk factor for cognitive decline; however, the association between long-term changes in HbA1c and cognitive performance remains underexplored, particularly in midlife. Leveraging repeated HbA1c measurements from young adulthood (ages 24–32) to midlife (ages 40–49) and assessments across multiple cognitive domains, we evaluated whether cumulative HbA1c and its trajectories were associated with cognitive performance in midlife.
This study used data from the National Longitudinal Study of Adolescent to Adult Health (Add Health), including up to 7,109 U.S. adults; analytic sample sizes varied across models depending on the availability of HbA1c measurements and cognitive assessments. HbA1c was measured at Waves IV–VI. Cognitive performance was assessed at Wave VI using four TestMyBrain (TMB) cognitive assessments: Verbal Paired Associates, Digit Symbol Matching, the Gradual Onset Continuous Performance Test, and Backward Digit Span. We estimated (1) OLS models using mean HbA1c across Waves IV–VI to capture cumulative glycemic exposure and (2) OLS models incorporating individual HbA1c intercepts and slopes derived from linear mixed-effects models to characterize long-term glycemic trajectories as predictors of Wave 6 cognitive performance. All models were adjusted for age, sex, race, and education, and incorporated survey weights.
Models using mean HbA1c indicated that greater cumulative glycemic exposure was associated with poorer cognitive performance. Similarly, trajectory-based models demonstrated that steeper increases in HbA1c over time (slope) were associated with worse performance on these tests at Wave VI. These findings suggest that sustained glycemic exposure and long-term increases in HbA1c from young adulthood to midlife are associated with poorer cognitive performance in specific cognitive domains at midlife, including processing speed and executive function, underscoring the importance of early and sustained metabolic control for cognitive health.