Effects of acute and long-term exercise modalities and doses on brain-derived neurotrophic factor in patients with stroke: a Bayesian network meta-analysis.

Objective: To systematically evaluate the effects of exercise interventions on brain-derived neurotrophic factor (BDNF) in patients with stroke, and to examine the dose-response relationships associated with acute and long-term exercise. Methods: PubMed, Embase, Web of Science, the Cochrane Library, and APA PsycINFO were searched for studies of exercise interventions in patients with stroke that reported BDNF outcomes. Risk of bias was assessed using RoB 2.0 and ROBINS-I. A network dose-response meta-regression was conducted within a Bayesian random-effects framework. Results: Twenty-three studies involving 903 participants were included, comprising 14 randomized controlled trials, 8 non-randomized studies, and 1 randomized crossover trial. Acute overall exercise showed a modest positive trend at lower dose levels; however, at a dose of 250 METs⋅min/week, the 95% credible interval included zero, indicating substantial uncertainty regarding whether a single bout of low-dose exercise produces a reliable increase in BDNF. For long-term overall exercise, posterior estimates generally favored a positive BDNF response as dose increased. The 95% credible interval first no longer included zero at 1300 METs⋅min/week, and estimates at 1700, 2000, 2300, and 2700 METs⋅min/week remained compatible with positive effects. However, these findings should be interpreted cautiously because the evidence base was limited and precision varied across dose levels. Clear differences were also observed across long-term exercise modalities. Multicomponent exercise showed the most favorable directional pattern across the 1700-2700 METs⋅min/week range, although several estimates were imprecise and the apparent advantage of this modality should be regarded as exploratory. By contrast, walking, cycling, and exercise combined with cognitive training all showed positive directional trends, but the 95% credible intervals included zero across dose levels, indicating substantial uncertainty regarding these modality-specific effects. Conclusion: The effects of exercise on BDNF in patients with stroke are jointly shaped by intervention duration, dose level, and exercise modality. Compared with acute exercise, long-term exercise at moderate-to-high doses, particularly multicomponent exercise, may be associated with a more favorable BDNF response. However, because the certainty of evidence was mostly moderate to low or very low and publication bias was detected, these findings should be considered preliminary and hypothesis-generating rather than definitive exercise prescription recommendations. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261350793, identifier CRD420261350793.