Abstract MP66: Prediabetes, Diabetes By Age Of Onset And Subsequent Risk Of Dementia

Objective: To characterize the direct and indirect association of prediabetes with dementia risk and to examine the age at diabetes onset and subsequent risk of dementia. Methods: At baseline (1990-1992), prediabetes was defined based on HbA1C 5.7-6.4% among people without a history of diagnosed diabetes or medication use for diabetes; diabetes was defined based on self-reported physician diagnosis or diabetes medication use or HbA1C level of 6.5% or greater. Incident diabetes with the same definition during the follow-up was included as a time-varying variable. Incident dementia was ascertained using surveillance, interviews and adjudication. Survival analysis used age as the time scale using an origin at age 50 and left and right censoring. Adjustment models included sex, race, education, APOE, BMI, smoking status, alcohol use, physical activity, total cholesterol, HDL cholesterol and hypertension. Results: Among the 13,388 participants, 2314 (17.3%) had prediabetes and 1798 (13.4%) had diabetes at baseline. Before adjusting for incident diabetes, the adjusted hazard ratios of dementia were 2.35 (95% CI: 1.99, 2.76) and 1.13 (95% CI: 1.02, 1.25) for diabetes and prediabetes compared to no diabetes in the fully adjusted model. After adding incident diabetes, the excess risk of dementia for prediabetes decreased by ~50% and the association was not significant. The relative hazards of dementia were 3.16 (95% CI: 2.15, 4.66), 1.64 (95% CI: 1.36, 1.97), 1.29 (95% CI: 1.14, 1.47) and 1.06 (95% CI: 0.89, 1.28) for diabetes with age onset at < 60, 60-69, 70-79 and 80-93, respectively (Table). Conclusion: Midlife diabetes and prediabetes are associated with excess hazard of dementia and death. Earlier age of onset of diabetes shows a strong dose response with higher dementia hazard. Much of the risk of dementia in pre-diabetes is explained by intervening incidence of clinical diabetes. Dementia prevention efforts would benefit from preventing or delaying the progression of prediabetes to diabetes.