Exercise effects on cognitive function and molecular markers in post-stroke patients with cognitive impairment: a systematic review and meta-analysis
Clinical Snapshot
PICO Framework
| P — Population | Post-stroke patients with cognitive impairment (PSCI) |
| I — Intervention | Exercise therapy (aerobic exercise, cognitive-motor dual-tasking, functional motor training) |
| C — Comparator | Control groups (standard care or no exercise intervention) |
| O — Outcomes | Cognitive function, motor function, activities of daily living, molecular biomarkers (BDNF, GSH, NSE, IL-6) |
Bottom Line
This comprehensive meta-analysis of 44 RCTs involving 4,450 post-stroke cognitive impairment patients demonstrates that structured exercise interventions, particularly combined aerobic and task-based training, significantly improve cognitive function (large effect size SMD=1.18), motor function, and activities of daily living. The study uniquely shows corresponding beneficial changes in molecular biomarkers including increased BDNF and GSH, and decreased inflammatory marker IL-6. These findings support implementing multimodal exercise programs in stroke rehabilitation, though clinicians should note the abstract lacks heterogeneity assessment and detailed methodology. The large effect sizes and biological plausibility through biomarker changes provide strong evidence for exercise prescription in post-stroke cognitive rehabilitation, particularly relevant for Australian multidisciplinary stroke teams.
Key Findings
P Value: Not reported in abstract
Effect Size: SMD = 1.18 (large effect)
Primary Outcome: Cognitive function improvement with combined aerobic and task-based exercise
Nnt Or Sensitivity: Motor function improvement MD = 13.98 points, ADL improvement MD = 16.78 points
Confidence Interval: 95% CI (0.68, 1.68)
Clinical Application
Combined aerobic and cognitive-motor training programs feasible in most rehabilitation facilities Relevant to Australian stroke rehabilitation pathways, aligns with ACSQHC stroke guidelines, may inform PBS-funded allied health interventions Post-stroke patients with cognitive impairment in rehabilitation settings
Abstract
INTRODUCTION: Exercise may improve cognitive function in stroke survivors. However, no study has yet examined the most effective exercise modalities and associated changes in biomarkers. This study aims to investigate the effects of different exercise types on cognitive function and biomarker trends, providing evidence-based guidance for early rehabilitation interventions. METHODS: Data from randomized controlled trials were collected from January 1, 2000, to March 6, 2025, using medical subject headings combined with free-text terms from PubMed, Cochrane Library, Embase, Wanfang, CNKI, CSTJ, and the China Medical Information Database. The Cochrane Risk of Bias Tool was used to assess the quality of the studies. Review Manager version 5.4.1 was employed to conduct all statistical syntheses. RESULTS: The forty-four original studies involving 4,450 patients with PSCI(Post-stroke cognitive impairment) were analyzed. Subgroup analysis by exercise intervention type revealed larger effect sizes when combining aerobic exercise with other task-based interventions(cognitive-motor dual-tasking and functional motor training) [SMD = 1.18, 95% CI (0.68, 1.68)]. Patients also showed improvements in motor function [MD = 13.98, 95% CI (10.06, 17.89)] and activities of daily living [MD = 16.78, 95% CI (12.97, 20.58)]. Concerning molecular biomarkers, serum levels of brain-derived neurotrophic factor (BDNF), glutathione (GSH), and neuron-specific enolase (NSE) increased significantly, whereas interleukin-6 (IL-6) levels decreased notably in PSCI patients following exercise therapy. CONCLUSION: Structured exercise effectively improves cognitive recovery, motor skills, and daily functioning in patients with PSCI. These clinical gains are accompanied by favorable peripheral biomarker modulations, characterized by significantly increased serum BDNF and GSH, as well as markedly decreased IL-6 levels.
References
- 1.Li, Y., Zhang, X., Yang, Y., Yun, J., Yang, X., Han, D., Wen, P., & Ren, C. (2026). Exercise effects on cognitive function and molecular markers in post-stroke patients with cognitive impairment: a systematic review and meta-analysis. Neurological Sciences. https://doi.org/10.1002/14651858.CD003316
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