Across four major aging cohorts — HRS (USA), ELSA (UK), SHARE (Europe), and MHAS (Mexico) — adults who maintained higher physical activity trajectories over time faced a 25% lower risk of transitioning from normal cognition to mild cognitive impairment (pooled HR = 0.75, 95% CI 0.65–0.87) and a 13% lower risk of MCI progressing to dementia (pooled HR = 0.87, 95% CI 0.77–0.98). Regional effects were notable: European cohorts showed the strongest protection against MCI onset (41% risk reduction), while the US cohort showed a 19% reduction in MCI-to-dementia progression.
What distinguishes this work from prior cross-sectional evidence is its trajectory-based design — capturing sustained behavioral patterns rather than single time-point snapshots — combined with a multistate Markov model that explicitly maps directional transitions between cognitive states. This methodological approach is considerably more informative for understanding disease progression dynamics. The multinational breadth strengthens generalizability, though moderate heterogeneity (I² ~52–58%) in some transitions signals that cultural, measurement, or healthcare-access differences meaningfully shape outcomes.
A key limitation: physical activity was self-reported and classified into just two trajectory groups, which likely obscures dose-response nuances. The null finding for MCI reversal is clinically important — activity appears to delay progression but not reverse established impairment. For adults in midlife and beyond, this adds multinational confirmatory weight to existing guidelines: sustained moderate-to-vigorous activity is among the most evidence-backed strategies for preserving cognitive function into old age.