Abstract / Summary
Abstract Background Stroke is the second leading cause of disability and death worldwide. Approximately 40%–60% of patients with stroke develop persistent working memory (WM) impairment, which severely compromises daily functioning. Moderate-intensity aerobic exercise (EX) and hyperbaric oxygen (HBO) therapy have been shown to improve poststroke cognition; however, their comparative efficacy and the potential added benefit of combining them remain unclear. We aimed to compare the effects of three intervention regimens on WM in older patients with stroke and explore the underlying mechanisms involving neurotrophic factors and prefrontal oxygenation. Methods This randomized controlled trial was conducted at The Sixth Hospital of Wuhan between January and December 2025. Thirty-six older patients with stroke of 6–12 months’ duration were randomly assigned to the control (CON), EX, HBO, or combined intervention (HBO + EX) group. All groups underwent a 2-week intervention. Preintervention and postintervention assessments included reaction time (RT) during the n-back task, oxyhemoglobin (O₂Hb) changes in the bilateral dorsolateral prefrontal cortices (DLPFCs) measured using functional near-infrared spectroscopy, and serum brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) levels measured using enzyme-linked immunosorbent assays. Results Compared with the CON group, all three intervention groups showed significant reductions in postintervention RT ( p < 0.05 ), with significantly greater improvement in the HBO + EX group than in the EX and HBO groups ( p < 0.01 ). Serum BDNF and VEGF levels increased significantly in all intervention groups ( p < 0.05 ), with the greatest VEGF increase in the HBO + EX group. Mean and peak O₂Hb levels in the left DLPFC (DLPFC-L) decreased significantly in all intervention groups ( p < 0.05 ), and these changes independently predicted RT improvement ( p < 0.01 ). Conclusions Moderate-intensity EX and HBO therapy improved WM in older patients with stroke, and their combination exerted a synergistic effect. These improvements were associated with increased BDNF and VEGF levels and improved oxygenation efficiency in the DLPFC-L. Changes in DLPFC-L oxygenation independently predicted WM recovery. Trial registration: ClinicalTrials.gov NCT07772947, registered on August 14, 2026. Retrospectively registered.