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

Abstract

Abstract 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.