Supplementary Material for: Remote Ischemic Conditioning on Cognitive Impairment in Patients with Cerebrovascular Disease: A Systematic Review and Meta-Analysis

Abstract Introduction: Cognitive impairment is a major complication of cerebrovascular diseases (CVDs), significantly affecting patients’ quality of life. With limited approved pharmacological interventions, non-pharmacological approaches, such as remote ischemic conditioning (RIC), have emerged as potential therapeutic strategies. This systematic review and meta-analysis aimed to evaluate the efficacy of RIC in improving cognitive function in patients with CVDs. Methods: Following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we conducted comprehensive searches across PubMed, Embase, the Cochrane Library (CENTRAL), and Web of Science for relevant studies published up to April 30, 2025. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Pooled estimates were calculated using random-effects models, accounting for heterogeneity. Results: Seven studies, involving 302 participants, met the inclusion criteria. Meta-analysis demonstrated that RIC significantly improved global cognitive performance (SMD 0.65, 95% CI 0.41-0.90, P<0.00001). Notable improvements were observed in visuospatial and executive functions (SMD 0.61, 95% CI 0.33-0.89, P<0.0001). However, no significant effects were found in other cognitive domains, including naming, attention, language, abstract reasoning, delayed recall, and immediate memory. Heterogeneity across studies varied by outcome. Conclusion: RIC shows promise for improving visuospatial/executive functions in cerebrovascular disease (SMD=0.47, p<0.001), though effects in other cognitive domains remain inconclusive. Large-scale trials with comprehensive assessments, mechanistic neuroimaging, and extended follow-up are needed to establish sustained clinical benefits.