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Introduction Sedentary behavior threatens cognitive health, yet evidence on the effects of physical activity interruptions is inconsistent. This systematic review synthesizes existing findings and clarifies key sources of heterogeneity. It aims to provide evidence-based insights to inform the development of effective interventions that promote brain health. Methods Following the PRISMA guidelines, we systematically searched four databases, PubMed, Web of Science, Cochrane, and Scopus, from inception to August 2025 for studies examining the effects of physical activity breaking up sedentary behavior on cognitive function. Three independent researchers performed literature screening, data extraction, and risk-of-bias assessment. A qualitative synthesis was conducted to synthesize the included studies. Results A total of 25 studies were included, including 19 randomized crossover trials and 6 randomized controlled trials. These encompassed 31 intervention protocols involving 707 participants. The overall risk of bias across the included studies was moderate. Qualitative synthesis revealed that interrupting sedentary behavior with physical activity acutely improves cognitive function following sedentary periods. Among the 23 studies examining acute effects, 15 (65%) reported significant cognitive improvements following the interruption of sedentary behavior. These improvements were observed most prominently in executive function (reported in 15 of 20 studies) and attention. Among various interventions, interrupting sedentary behavior every 30 min with moderate-to-vigorous intensity walking or stair climbing during prolonged sitting sessions lasting 3–7 h was most effective. However, current evidence is insufficient to establish its chronic impact on cognitive function. Potential mechanisms may primarily involve glycemic control and metabolic regulation; hemodynamic responses and maintenance of cerebral blood flow; and neurotrophic signaling and myokine release following the interruption of sedentary behavior by physical activity. Heterogeneity in the qualitative synthesis was primarily driven by the variations in participant age (ranging from 4 to 77 years), exercise duration (30 s to 1 h), and intervention frequency (ranging from every 4 min to every 3 h). Conclusion Interrupting sedentary behavior with physical activity acutely improves cognitive function and promotes brain health. Future studies with longer intervention and follow-up periods are needed to investigate the potential for sustained cognitive benefits. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251162102 , Identifier CRD420251162102.
Li et al. (2026) studied this question.