Objective: To investigate the effects of the three kinds of anti-amyloid-β (Aβ) drugs on cognitive and other functions, fluid and neuroimaging biomarkers, and safety on patients with Alzheimer's disease (AD), and rank the three kinds of anti-Aβ drugs.
Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and AlzForum from inception to January 21, 2023 to include randomized controlled clinical trials. Random effects meta-analyses were performed.
Results: Forty-one clinical trials (20929 participants, 9167 male) were included. Anti-Aβ drugs had significant but relatively low efficacy in preventing cognitive decline (ADAS-Cog SMD -0.07, 95% CI: -0.10 to -0.03, p < 0.001; CDR-SOB -0.05, -0.09 to -0.01, p = 0.017). Instrumental variable meta-analysis and trial sequential analysis confirmed the reliability of the pooled estimation. Beneficial effects were also observed by assessing other cognitive and activity of daily living scales and biomarkers, with acceptable safety of anti-Aβ drugs. Meta-regression demonstrated significant association between higher baseline mini-mental statement examination scores (MMSE) and better cognitive protective effects on cognitive function (ADAS-Cog β: -0.02, -0.05 to 0.00, p = 0.017) and clearance of pathological productions of anti-Aβ drugs. Network meta-analysis ranked the passive immunotherapy drugs to have the best cognitive efficacy, followed by active immunotherapy and small molecule drugs.
Conclusion: Anti-Aβ drugs have relatively low efficacy in preventing cognitive decline, and they reduce pathological productions with acceptable safety. Patients with higher baseline MMSE scores benefit more from anti-Aβ drugs. Passive immunotherapy anti-Aβ drugs show relatively better efficacy than active immunotherapy and small molecule anti-Aβ drugs.
Keywords: Alzheimer’s disease; Amyloid-β; Clinical trial; Meta-analysis.
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