Abstract
INTRODUCTION: Cognitive impairment is a core feature of major depressive disorder (MDD) that often persists during remission, significantly affecting psychosocial functioning. While exercise is known to alleviate depressive symptoms, its specific impact on cognitive domains remains variable. This study aims to evaluate the dose-response relationship and comparative effectiveness of different types of exercise interventions on cognitive function in adults with MDD. METHODS: Five electronic databases (Ovid Medline, PsycINFO, Web of Science, Cochrane Central, and Embase) were systematically searched on September 20, 2024. STUDY SELECTION: Randomized controlled trials (RCTs) involving adults aged 18 years or older with MDD were included if they examined the effects of exercise interventions and reported at least one cognitive outcome. Two independent reviewers conducted data extraction and quality assessment according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Network Meta-Analyses (PRISMA-NMA) guidelines. RESULTS: A three-level meta-analysis and a Bayesian model-based network meta-analysis were performed. Fifteen RCTs with a total of 1,196 participants were included. A non-linear dose-response relationship was observed, with a minimum effective dose of 967 METs-min/week-within the WHO-recommended exercise range. Among exercise types, Tai Chi/Qigong demonstrated the greatest cognitive benefits. Moderation analysis indicated that younger age and a higher proportion of female participants were associated with stronger cognitive effects. CONCLUSION: Exercise significantly improves cognitive function in adults with MDD, with aerobic and mind-body exercises offering particularly strong benefits. These results support the integration of tailored exercise programs into treatment strategies for cognitive dysfunction in MDD. SYSTEMATIC REVIEW REGISTRATION: The systematic review was registered in PROSPERO (CRD42024546289): https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024546289.