Objective To assess the efficacy and safety of Aβ-targeting agents for mild to moderate Alzheimer’s disease.
Methods The MEDLINE, Embase, Cochrane Central Register of Controlled Trials, PsycINFO, ClinicalTrials.gov and the WHO’s International Clinical Trials Registry Platform search portal were searched from their inception to April 2020. We generated pooled estimates using random effects meta-analyses.
Results Nineteen randomised controlled trials, of which 17 had a low risk of bias, included 12 903 participants. The meta-analysis showed no difference in the cognitive subscale of Alzheimer’s Disease Assessment Scale (ADAS-Cog) between anti-Aβ drugs and placebo (mean difference (MD): 0.20, 95% CI −0.40 to 0.81; I 2=99.8%; minimal important difference 3.1–3.8 points, moderate-certainty evidence). For ADAS-Cog, results suggested that one drug that increases Aβ clearance may differ in effect (MD: −0.96, 95% CI −0.99 to −0.92) from drugs that reduce Aβ production (MD: 0.78, 95% CI 0.25 to 1.32) (interaction p<0.000001); this difference also existed in the outcome of MMSE and CDR-SOB. Compared with placebo, anti-Aβ drug-related adverse events were as follows: anxiety, depression, diarrhoea, fatigue, rash, syncope and vomit.
Discussion From current evidence, anti-Aβ interventions are unlikely to have an important impact on slowing cognitive or functional decline. Although the subgroup analysis suggested possible benefits from Aβ clearance drugs, the analysis has limited credibility, and a benefit from drugs that increase clearance, if real, is very small.
Trial registration number PROSPERO registration number CRD42019126272.
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LL, XZ, SW and CT contributed equally.
Contributors Study concept and design: NX, CT and LL. Acquisition of data: XZ and GY. Analysis and interpretation of data: LL, JZ, SG, HW and MX. Drafting of the manuscript: LL, XZ, SW and YZ. Critical revision of the manuscript for important intellectual content: GG, NX and CT. All authors critically revised successive drafts of the paper and approved the final version.
Funding This study was supported by the Youth Scientific Research Training Project of GZUCM (2019QNPY02), the National Natural Science Foundation of China (81873375), the Young Top Talent Project of Scientific and Technological Innovation in Special Support Plan for Training High-level Talents in Guangdong (2017TQ04R627), the Key Program of the First-Class Discipline of Guangzhou University of Chinese Medicine (XK2018001), the Key Laboratory Program of Universities in Guangdong Province (2018KSYS006) and the Natural Science Foundation of China(81904275).
Competing interests None declared.
Patient consent for publication Not required.
Provenance and peer review Not commissioned; externally peer reviewed.
Data availability statement All data relevant to the study are included in the article or uploaded as supplementary information. Data are available to qualified investigators on request to the corresponding author.
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