Abstract DP183: Association between Cumulative Fasting Blood Glucose and Later-life Cognitive Decline

Background: Diabetes, particularly in midlife, is a risk factor for dementia. However, how cumulative fasting blood glucose (FBG) levels contribute to dementia risk is unclear. Objective: To determine associations between cumulative FBG levels and cognitive decline. Methods: We pooled data from 15,294 individuals aged 18 or older without dementia or stroke (55% women; mean [SD] age at first cognitive assessment 52 [21] years) from 6 cohorts (1971 to 2024): Atherosclerosis Risk in Communities Study (ARIC), Coronary Artery Risk Development in Young Adults (CARDIA) Study, Cardiovascular Health Study (CHS), Framingham Offspring Study (FOS), Multi-Ethnic Study of Atherosclerosis (MESA), and Northern Manhattan Study (NOMAS). Controlling for other known risk factors for dementia, we used linear mixed effects models to examine the association between time-dependent cumulative mean FBG level and trajectories of harmonized global cognition (primary outcome), memory, and executive function. Cognitive outcomes were standardized as T-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Higher scores indicate better performance. Median (IQR) follow-up was 23 (9, 36) years. The median (IQR) number of FBG measurements was 5 (2, 7) and the median (IQR) time between first and last FBG measurement was 9 (5, 30) years. Results: Higher time-dependent cumulative mean FBG level was associated with significantly faster declines in global cognition (-0.004 points per year faster per each 10 mg/dL increase [95% CI, -0.007 to -0.001]; P=0.006), memory (-0.014 points per year faster per each 10 mg/dL increase [95% CI, -0.021 to -0.008]; P