Anti-Amyloid Antibodies in the Treatment of Alzheimer’s Disease: An Umbrella Review

Background: Over the last decade, numerous studies have investigated the administration of monoclonal anti-amyloid antibodies (AAAs) as a therapeutic approach in Alzheimer’s disease (AD). The purpose of this umbrella review is to summarize current knowledge concerning the efficacy and safety of FDA- and EMA-approved AAAs for AD, namely, lecanemab and donanemab. Methods: We conducted a literature search in the PubMed, Scopus, and Web of Science databases in English, focusing on systematic reviews and/or meta-analyses, assessed by AMSTAR 2, concerning clinical and imaging efficacy, i.e., cognitive improvement and reduction of beta-amyloid on PET scan, as well as safety, i.e., adverse events and amyloid-related imaging abnormalities (ARIA). The extracted review-level dataset was entered into SPSS Version 26 for descriptive statistical analysis. Results: This umbrella review included 11 systematic reviews and/or meta-analyses. Patients treated with lecanemab or donanemab showed statistically significant changes on cognitive scales such as the Clinical Dementia Rating-Sum of Boxes (CDR-SB) (mean effect estimate −0.485, SD = 0.152, −0.70 to −0.34) and the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), but most were below or around clinically meaningful thresholds. Lecanemab and donanemab showed a statistically significant decrease in amyloid PET outcomes, including centiloids or the standardized uptake value ratio. Both antibodies were linked to ARIA, including amyloid-related imaging abnormalities-edema (ARIA-E OR 8.32–12.26) and amyloid-related imaging abnormalities-hemorrhage (ARIA-H OR 2–5.77), especially in ApoEε4 carriers. Conclusions: Lecanemab and donanemab are biologically active drugs for the treatment of early AD, with cognitive benefits below or around the clinically meaningful threshold. They are, however, associated with increased ARIA risk. Their administration depends upon careful patient selection, shared decision-making, and clear communication regarding expectations.