Impact of antidiabetic therapy on cognitive function in patients with type 2 diabetes and Alzheimer's disease: A comprehensive analysis

BackgroundSeveral hypotheses suggest that type 2 diabetes mellitus (T2DM) is a risk factor for Alzheimer's disease (AD), and antidiabetic medications may influence cognitive function in these patients.ObjectiveThis study aims to provide a comprehensive evaluation of the impact of single and combination antidiabetic therapies on cognitive function in patients with both AD and T2DM.MethodsWe analyzed data from the National Alzheimer's Coordinating Center (NACC), covering a 17-year period from June 2005 to August 2022. This study included 3234 patients with both AD and T2DM. After applying exclusion criteria, 964 patients were analyzed using propensity score matching and a generalized linear mixed model. Patients were categorized based on their longitudinal use of oral antidiabetic medications.ResultsBased on the 964 patients' cohort, the study found that patients receiving metformin with sulfonylureas (RR = 1.105 [1.022, 1.195], p = 0.013) and metformin with a dipeptidyl peptidase 4 inhibitor (DPP-4i) (RR = 1.132 [1.021, 1.256], p = 0.019) experienced a significantly slower decline in MMSE scores over time when compared to patients receiving metformin with thiazolidinediones (TZD).ConclusionsThis study demonstrates that combination therapies involving metformin with sulfonylureas or DPP-4i are associated with a slower rate of cognitive decline compared to metformin with TZD in patients with AD and T2DM. These findings provide novel evidence for the long-term cognitive benefits of specific antidiabetic therapies and offer valuable insights for clinical decision-making in this dual-affected population.