286-OR: Biomedical Predictors of Cognitive Decline in Older Participants with T1DM: Longitudinal Follow-Up of the DCCT/EDIC Cohort

Abstract

DCCT/EDIC participants have been followed for an average of 32 years (N=1,054; mean age 60±7 years; duration T1DM 38±5 years). To evaluate cognitive function in T1DM, mental efficiency and memory were assessed five times during the study. Standardized z-scores were calculated relative to the DCCT baseline evaluation and averaged to obtain three summary domain scores (immediate recall, delayed recall, mental efficiency). Generalized linear mixed models were used. In 2018, mean HbA1c levels were 7.9±0.9% and 46% of participants had experienced ≥1 hypoglycemic coma/seizure. Adjusted for age, sex, and education, cognition declined over time (p<0.0001 each domain). In multivariable analysis, higher mean HbA1c (β±SE, -0.105±0.017 per 1%, p<0.0001), higher mean systolic blood pressure (-0.083±0.013 per 5 mmHg, p<0.0001), and history of coma/seizure (-0.175±0.041 ≥1 vs. none, p<0.0001) were independently associated with declining mental efficiency. Decreased mental efficiency was also associated with microalbuminuria (AER ≥30 mg/hr), lower levels of HDL cholesterol, and higher daily insulin dose (u/kg/day) (each p<0.0001). Biomedical predictors did not influence recall. These findings demonstrate the effects of increasing age, glycemic excursions (chronic hyperglycemia and clinically-significant hypoglycemia), and blood pressure on mental efficiency. Disclosure A.M. Jacobson: None. C.M. Ryan: None. B.H. Braffett: None. R. Gubitosi-Klug: None. G.M. Lorenzi: None. J.A. Luchsinger: Consultant; Self; vTv Therapeutics. V.R. Trapani: None. I. Bebu: None. N. Chaytor: Consultant; Self; Eli Lilly and Company. S.M. Hitt: None. K. Farrell: Stock/Shareholder; Spouse/Partner; Dexcom, Inc., Tandem Diabetes Care. J.M. Lachin: Board Member; Self; Tolerion, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases