Pharmacological interventions targeting cognition and related clinical outcomes in vascular dementia: a systematic review and meta-analysis of randomized controlled trials.

PURPOSE: Randomized evidence for pharmacological interventions in vascular dementia (VaD) is fragmented. We conducted a VaD-focused, scale-specific systematic review and meta-analysis. METHODS: We searched four databases for English-language parallel-group randomized controlled trials (1990-2025). Comparable placebo-controlled outcomes were pooled using random-effects meta-analysis; non-poolable outcomes were synthesized according to SWiM. Risk of bias and certainty were assessed with RoB 2 and GRADE. RESULTS: Sixteen trials included 5,668 participants across trial cohorts; with one exception, all were published in 2012 or earlier. EGb 761® was evaluated in three trials; nimodipine, galantamine, memantine, and rivastigmine in two each; and pentoxifylline, citicoline, sulodexide, donepezil, and Tianzhi granule in one each. Galantamine reduced ADAS-Cog/11 scores (2 trials, n = 1,332; MD - 2.01, 95% CI - 3.18 to - 0.85) and ADAS-Cog/13 scores (2 trials, n = 1,328; MD - 2.51, 95% CI - 3.87 to - 1.15), and memantine reduced ADAS-Cog/11 scores (2 trials, n = 752; MD - 2.20, 95% CI - 3.24 to - 1.15); certainty was moderate. EGb 761® reduced SKT scores (3 trials, n = 283; MD - 2.65, 95% CI - 5.17 to - 0.12), but heterogeneity was extreme (I²=92.8%; very low certainty). Galantamine showed no clear NPI benefit (2 trials, n = 1,310; MD - 0.13, 95% CI - 4.05 to 3.79), and memantine showed no clear GBS benefit (2 trials, n = 595; MD - 1.93, 95% CI - 4.69 to 0.84). Evidence for the other seven interventions was mainly single-trial and non-poolable; functional and global outcomes did not establish consistent benefit. CONCLUSION: Galantamine and memantine showed small short-term cognitive effects; EGb 761® suggested a fragile, very low-certainty signal; patient-important benefits remain uncertain.