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.