This narrative review examines the molecular and systemic mechanisms by which exercise — acting as a non-photic zeitgeber — modulates circadian rhythms, and evaluates the therapeutic implications for two neurological diseases: stroke (ischemic, ICH, SAH) and Alzheimer's disease (AD).
Exercise enhances circadian amplitude, stability, and phase alignment via AMPK-SIRT1-BMAL1 signaling, PGC-1α-dependent mitochondrial regulation, and immune-clock coupling. In stroke, pre-stroke physical activity was associated with ~3.6× higher odds of mild neurological deficits at ICH onset and ~70% lower 30-day mortality. In AD, regular exercise reduces Aβ burden, shifts microglia toward anti-inflammatory states, and normalizes sleep-wake cycles in preclinical and observational data.
- Almost entirely based on preclinical (rodent) models and observational data; randomized controlled trials on circadian-targeted exercise in stroke or AD are lacking. - Optimal exercise timing, intensity, and duration for circadian benefit in neurological disease have not been established. - Individual variation by age, sex, chronotype, and disease stage is acknowledged but uncharacterized.
Appropriately timed, regular moderate exercise may improve circadian alignment and support neurological recovery in stroke and AD — consider it a behavioral chronotherapy adjunct, not just a fitness tool. Until optimal timing protocols are defined, encouraging habitual physical activity remains a low-risk, evidence-supported recommendation for patients with or at risk for these conditions.
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