Network meta-analysis of the efficacy of nine drugs for cognitive function in patients with Alzheimer's disease

Background Alzheimer's disease (AD) remains a global challenge, and the comparative cognitive efficacy of emerging pharmacotherapies is still unclear. Objective To compare and rank nine pharmacological agents against placebo in AD with respect to key cognitive outcomes using a network meta-analysis. Methods We systematically searched randomized controlled trials published up to May 2025 that evaluated aducanumab, lecanemab, donanemab, gosuranemab, semorinemab, tilavonemab, zagotenemab, masupirdine, or sodium oligomannate in AD. The primary outcomes were Clinical Dementia Rating–Sum of Boxes (CDR-SB) and Alzheimer's Disease Assessment Scale–Cognitive Subscale (ADAS-cog); Mini-Mental State Examination (MMSE) was a secondary outcome. Treatments were ranked using the Surface Under the Cumulative Ranking curve (SUCRA). Results Fifteen randomized trials encompassing 33 treatment arms were included. No drug demonstrated statistically robust superiority over placebo in primary outcomes. Semorinemab and tilavonemab achieved highest SUCRA rankings, but without significant pairwise advantage. For MMSE, aducanumab showed a modest mean difference versus placebo (1.98, 95% CI 0.03–3.93), though evidence of publication bias reduced confidence. Conclusions Current pharmacological treatments do not consistently outperform placebo in AD. Tau-targeted antibodies (semorinemab, tilavonemab) display modest but non-significant promise, whereas aducanumab's apparent benefit is likely confounded by publication bias. Further large, rigorous randomized controlled trials and improved preclinical models are essential.