Effects of exercise versus usual care on older adults with amnestic mild cognitive impairment: EXERT versus ADNI

Abstract INTRODUCTION EXERT was a multisite randomized controlled trial (RCT) examining the effects of moderate‐high intensity aerobic training (AX) versus lower‐intensity stretching/balance/range of motion (SBR) on cognitive trajectories in older adults with amnestic mild cognitive impairment (aMCI). METHODS Preplanned post‐hoc analyses were conducted to compare each arm to a propensity‐matched usual care (no intervention) group from Alzheimer's Disease Neuroimaging Initiative 1 (ADNI‐1) selected for similarity across key characteristics. Differences in 12‐month trajectories in the primary endpoint (ADAS‐Cog‐Exec) and magnetic resonance imaging (MRI) volumes in prespecified brain regions were compared. RESULTS AX and SBR showed significantly less 12‐month cognitive decline than ADNI‐1 (AX: n = 109, β = 0.169, 95% confidence interval [CI] 0.011–0.328; SBR: n = 105, β = 0.181, 95% CI 0.007–0.354). There were trends of less prefrontal cortex volume loss for both EXERT groups and less AD signature region volume loss for SBR relative to ADNI‐1 over 12 months. DISCUSSION Moderate‐high intensity aerobic or low‐intensity flexibility exercise for 12 months in participants with aMCI may provide protection against decline relative to usual care. CLINICAL TRIAL REGISTRATION The EXERT clinical trial is registered at clinicaltrials.gov (NCT02814526). Highlights EXERT was a randomized controlled trial in sedentary older adults with aMCI. EXERT arms were propensity‐matched to a usual care (no intervention) group (Alzheimer's Disease Neuroimaging Initiative 1 [ADNI‐1]). High and low‐intensity exercise arms had less 12‐mo cognitive decline than ADNI‐1. There were trends of less prefrontal cortex volume loss for each arm versus ADNI‐1.