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Introduction Cognitive–motor interventions have emerged as promising rehabilitation strategies to enhance neuroplasticity following stroke; however, their effects on circulating brain-derived neurotrophic factor (BDNF) remain incompletely understood. This systematic review and meta-analysis aimed to quantify the effects of cognitive–motor interventions on serum BDNF levels in adults and older adults after stroke. Methods A comprehensive literature search of MEDLINE/PubMed, Scopus, Cochrane, Web of Science (Core Collection), EBSCOhost, CINAHL, and ProQuest was conducted through December 2025. Randomized controlled trials evaluating cognitive–motor interventions and reporting serum brain-derived neurotrophic factor outcomes in post-stroke populations were included. Methodological quality and certainty of evidence were assessed according to PRISMA 2020 guidelines, the Oxford Centre for Evidence-Based Medicine framework, the RoB two tool, and GRADEpro. The review protocol was registered in PROSPERO (CRD420251140852). Results Nine randomized controlled trials involving 457 participants met the inclusion criteria. Meta-analysis demonstrated that cognitive–motor interventions elicited a statistically significant increase in serum BDNF levels compared with control conditions (Hedges’ g = 2.51; 95% CI: 0.97 to 4.06; p = 0.001; I 2 = 92%), indicating a large overall effect. Conclusion These findings suggest that cognitive-motor interventions may increase circulating BDNF levels after stroke, supporting their potential role in promoting neuroplastic mechanisms during rehabilitation; however, the very high heterogeneity across studies warrants cautious interpretation. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251140852 identifer, PROSPERO 2025 CRD420251140852.
Vásquez-Carrasco et al. (2026) studied this question.
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