2171-P: Trajectories of Physical Activity during the Mid- to Late-Life Transition and Cognitive Impairment in Persons with Prediabetes or Type 2 Diabetes

Introduction and Objective: PA, a lifestyle target for preventing and treating T2D, may lower risk of CI. We examined longitudinal trajectories of PA and their association with CI in the Diabetes Prevention Program Outcomes Study (DPPOS). Methods: Participants (n=1,560) at high T2D risk randomized to lifestyle, metformin, or placebo (1996-1999) had ~3y of active intervention (DPP) and ~21y of unmasked follow-up (DPPOS). CI status was determined ~25y post-randomization using NACC-UDS (v3) criteria. PA (metabolic equivalent [MET] hours/week) was assessed using the Modifiable Activity Questionnaire at up to 15 visits. Linear mixed-effects models summarized PA during the study period (mean and slope). Multinomial logistic regression assessed associations between PA parameters and CI risk (Dementia, Mild CI [MCI] vs no CI). Results: At cognitive assessment, participants were ~74 years (IQR 68-80); 72% women, and 71% had T2D. Higher mean PA was associated with 19% decreased odds of dementia per additional 10 MET-h/wk (Table, global p=0.023). PA slope was not associated with CI. No significant heterogeneity was observed by diabetes status at time of assessment. Conclusion: Higher mean PA over 21 years was associated with decreased risk of dementia. In the context of prediabetes and T2D, these findings underscore PA throughout mid- to late-life as a critical modifiable protective factor for dementia. Disclosure A.H. Tjaden: None. J.P. Crandall: None. H.P. Hazuda: None. E.M. Venditti: None. Q. Pan: None. B. Laferrère: Consultant; Ended; Azurity. E.S. Strotmeyer: Research Support; Current; Amgen Inc. O. Carmichael: Research Support; Current; Eli Lilly and Company. D. Dabelea: None. E. Groessl: None. W. Knowler: None. N. Nadkarni: None. J.M. Noble: None. B. Rockette-Wagner: None. J.A. Luchsinger: Consultant; Current; Merck KGaA, Novo Nordisk. Other - Merck KGaA provides investigational product including matching placebo free of charge for an NIH funded clinical trial.; Current; Merck KGaA. P. Palta: None. D. Research Group: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) U01 DK048489, National Institute on Aging of the NIH 5 U19 AG078558.