2177-P: Type 2 Diabetes Heterogeneity and Incident Dementia Risk Compared with Adults without Diabetes

Introduction and Objective: Type 2 diabetes (T2D), a heterogeneous disease with distinct subtypes, is associated with elevated dementia risk. However, it is unknown if subtypes (Mild Obesity-Related Diabetes MOD, Severe Insulin-Deficient Diabetes SIDD, Mild Age-Related Diabetes MARD) are differentially associated with incident dementia compared with adults without T2D. Methods: Adults (≥40 years; n = 878,094) with newly diagnosed T2D between 2012-2023 and no history of dementia were 1:1 matched on age, sex, smoking status, and BMI to those without diabetes in the Epic Cosmos database. Newly diagnosed T2D was classified into subtypes using reliable models (AUC: 0.81-0.99). Incident all-cause dementia (vascular, Alzheimer’s, and others) was identified using ICD-10-CM codes. Cox proportional hazards regressions, adjusted for covariates, estimated hazard ratios (HR). Results: The analytic sample was 65.8 years SD: 11.5 and 53% female. Over follow-up (median: 3.9 years IQR: 1.7-10.8), 47,058 were diagnosed with dementia. Relative to adults without diabetes, SIDD (HR: 1.55 1.47-1.64) and MARD (HR: 1.10 1.05-1.14) had elevated rates of dementia, while Mixed (HR: 1.04 0.97-1.12), and MOD (HR: 0.97 0.88-1.06) had similar rates (Figure). Conclusion: Relative to adults without diabetes, subtypes showed clinically meaningful differences in dementia risk. These findings underscore the importance of considering diabetes heterogeneity when evaluating dementia risk. Disclosure R.N. Ekanayake: None. Z. Li: None. J. Guo: None. D. Hua: None. T. Hung: None. J. Varghese: None.