Adjunctive hyperbaric oxygen therapy for post-stroke cognitive impairment: a systematic review and meta-analysis of randomized controlled trials
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Xiaosai Hu1, Shurong Zhao2, Dandan Zhang3
1School of Sports Medicine and Rehabilitation, Shandong First Medical University (Shandong Academy of Medical Sciences), Taian, China.
Objective:
To evaluate the effects of adjunctive hyperbaric oxygen therapy (HBOT) on cognitive, neurological, and functional outcomes in patients with post-stroke cognitive impairment (PSCI), and explore potential sources of heterogeneity.
Methods:
Eight databases were searched from inception to July 15, 2026. Randomized controlled trials (RCTs) evaluating adjunctive HBOT in patients with PSCI were included. The primary outcome was the Montreal Cognitive Assessment (MoCA); secondary outcomes included the Mini-Mental State Examination (MMSE), National Institutes of Health Stroke Scale (NIHSS), Modified Barthel Index (MBI), and Barthel Index (BI). Random-effects meta-analyses, prespecified subgroup analyses, and meta-regression were performed. Sensitivity analyses, funnel plots, Egger's tests, and GRADE assessments were conducted.
Results:
Thirty-five RCTs involving 3,036 participants, all conducted in China, were included. Adjunctive HBOT was associated with higher MoCA scores (MD = 2.90, 95% CI: 2.47-3.33; p < 0.00001; I 2 = 84%) and MMSE scores (MD = 2.68, 95% CI: 2.20-3.16; p < 0.00001; I 2 = 83%). Improvements were also observed in NIHSS (MD = -2.61, 95% CI: -3.34 to -1.89; p < 0.00001; I 2 = 93%), MBI (MD = 6.64, 95% CI: 3.76-9.52; p < 0.00001; I 2 = 82%), and BI (MD = 8.77, 95% CI: 4.72-12.82;p < 0.00001; I 2 = 82%). No statistically significant subgroup differences were observed for MoCA (p = 0.10) or MMSE (p = 0.43). Higher baseline MoCA scores tended to be associated with smaller treatment effects in meta-regression (β = -0.1411, p = 0.0637; R 2 = 15.42%). Substantial heterogeneity remained largely unexplained. Evidence certainty was low for MoCA, MMSE, and MBI and very low for NIHSS and BI.
Conclusion:
Adjunctive HBOT may provide cognitive and functional benefits in patients with PSCI. However, substantial unexplained heterogeneity, low-to-very-low certainty of evidence, and the exclusively Chinese evidence base warrant cautious interpretation and limit generalizability. Further well-designed RCTs involving diverse populations are needed.
Systematic Review Registration:
https://www.crd.york.ac.uk/PROSPERO/view/CRD420261473579, PROSPERO, CRD420261473579.