{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T20:02:21Z","timestamp":1788292941426,"version":"build-2803163510"},"reference-count":64,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Donanemab, a monoclonal antibody targeting amyloid-\u03b2 (A\u03b2) plaques, has shown the ability to reduce cerebral amyloid burden in early Alzheimer's disease (AD). However, uncertainties remain regarding its clinical relevance, particularly in relation to tau pathology,\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 genotype, and methodological limitations in existing trials.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To conduct a systematic review and exploratory meta-analysis to evaluate the efficacy, safety, and tolerability of donanemab in patients with mild to moderate AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We conducted a systematic review and exploratory meta-analysis following PRISMA guidelines. Randomized controlled trials comparing donanemab to placebo in individuals aged \u226565 years with biomarker-confirmed mild to moderate AD were included. Outcomes included cognitive measures (ADAS-Cog13, MMSE, CDR-SB, iADRS, ADCS-iADL) and adverse events (ARIA-E, ARIA-H, infusion reactions, discontinuations). Random-effects models were used to estimate pooled mean difference (MD) or risk ratio (RR) with 95% confidence intervals. Subgroup analyses were performed by baseline tau burden and\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 genotype.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three trials (n\u2009=\u20092054) were included. Donanemab modestly reduced cognitive decline compared to placebo: ADAS-Cog13 (MD, \u22121.86), CDR-SB (MD, \u22120.36), MMSE (MD, 0.64), and iADRS (MD, 3.19), with similar effects across tau subgroups. The risk of ARIA-E was markedly increased (RR, 12.39), especially among\n                      <jats:italic>APOE<\/jats:italic>\n                      \u03b54 homozygotes. Infusion reactions (RR, 11.90) and discontinuations (RR, 3.22) were also more frequent.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Donanemab demonstrated modest cognitive benefits, the clinical significance of which remains uncertain. Independent, longer-term trials with rigorous methodology and active comparators are warranted to more clearly define its therapeutic value in the treatment of AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877251361044","type":"journal-article","created":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T06:55:44Z","timestamp":1753167344000},"page":"477-493","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Efficacy and\n                    <i>APOE<\/i>\n                    \u03b54-stratified risk of donanemab in Alzheimer's disease: A systematic review and meta-analysis of randomized clinical trials"],"prefix":"10.1177","volume":"107","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-4789-6019","authenticated-orcid":false,"given":"Anderson Matheus","family":"Pereira da Silva","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Falc\u00e3o","sequence":"additional","affiliation":[{"name":"Department of Medicine, Bahiana School of Medicine and Public Health, Salvador, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-6624","authenticated-orcid":false,"given":"Filipe","family":"Virgilio","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Bar\u00e3o de Mau\u00e1 University Center, Ribeir\u00e3o Preto, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Rodrigues Menezes","sequence":"additional","affiliation":[{"name":"Department of Medicine, State University of Rio Grande do Norte, Rio Grande do Norte, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-1438","authenticated-orcid":false,"given":"Marianna","family":"Leite","sequence":"additional","affiliation":[{"name":"Department of Medicine, Santa Marcelina College, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Farias","sequence":"additional","affiliation":[{"name":"Department of Medicine, Federal University of Roraima, Boa Vista, Roraima, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8262-5947","authenticated-orcid":false,"given":"Maria","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8291-6474","authenticated-orcid":false,"given":"Mariana","family":"Lee Han","sequence":"additional","affiliation":[{"name":"Department of Medicine, Medical School of the University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9322-0405","authenticated-orcid":false,"given":"Jo\u00e3o Paulo","family":"Mota Telles","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of S\u00e3o Paulo, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5864-7980","authenticated-orcid":false,"given":"Eryvelton","family":"de Souza Franco","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Bernadete","family":"de Sousa Maia","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Federal University of Pernambuco, Recife, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,9]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.937486"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-016-0188-8"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-191300"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2011.05.2410"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(21)00277-2"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.14283\/jpad.2020.24"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1819.2009.01955.x"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-022-00292-3"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2023.13239"},{"key":"e_1_3_3_11_2","article-title":"Donanemab (LY3002813) dose-escalation study in Alzheimer's disease","volume":"7","author":"Lowe SL","year":"2021","unstructured":"Lowe SL, Willis BA, Hawdon A, et al. 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