{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:06:03Z","timestamp":1789049163582,"version":"build-2803163510"},"reference-count":43,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,16]],"date-time":"2026-08-16T00:00:00Z","timestamp":1786838400000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Brain and Behavior"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with limited treatment options. Gantenerumab, a \u03b2\u2010amyloid\u2013targeting monoclonal antibody, has shown mixed clinical results. With new trial data available, this updated systematic review and meta\u2010analysis re\u2010evaluates its efficacy and safety in early AD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Registered on PROSPERO (CRD420251082463) under PRISMA guidelines, we searched PubMed, Cochrane Library, and Google Scholar from inception to October 2025 for randomized trials in early AD comparing gantenerumab with placebo. A random\u2010effects model assessed pooled outcomes with heterogeneity (\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      ) and sensitivity analyses. Additionally, meta\u2010regression and certainty of evidence using Gradepro were performed. Risk of bias was evaluated using the Cochrane tool. An Institutional Review Committee (IRC) and its Ethical Review Board (ERB) approval was not required.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Six trials (3103 participants: 1718 gantenerumab; 1385 placebo) were included. Gantenerumab showed no significant effect on CDR\u2010SB (MD\u00a0=\u00a0\u22120.07; 95% CI: \u22120.34\u20130.20;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.62;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a016%) but produced small improvements in FAQ (MD\u00a0=\u00a0\u22120.73; 95% CI: \u22121.30 to \u22120.17;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0\n                      <jats:italic>=<\/jats:italic>\n                      \u00a00.01;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00%) and Amyloid\u2010PET score (MD\u00a0=\u00a0\u221245.67; 95% CI: \u221288.09 to \u22123.24;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0\n                      <jats:italic>=<\/jats:italic>\n                      \u00a00.03;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a099%). While significant statistical improvement was seen in the ADAS\u2010Cog13 score (MD\u00a0=\u00a0\u22120.95; 95% CI: \u22121.76 to \u22120.13;\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0\n                      <jats:italic>=<\/jats:italic>\n                      \u00a00.02;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u00a0=\u00a00%), the effect sizes for both FAQ and ADAS\u2010Cog13 fell below established MCID thresholds. MMSE and ADCS\u2010ADL showed no significant differences. Safety analysis revealed higher risks of ARIA\u2010E (RR\u00a0=\u00a05.51), ARIA\u2010H (RR\u00a0=\u00a01.73), and injection site reactions (RR\u00a0=\u00a02.15), with no differences in other adverse events.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Gantenerumab significantly reduces amyloid and statistically improves select functional (FAQ) and cognitive (ADAS\u2010Cog13) measures in early AD; however, these changes remain below accepted MCID thresholds, indicating a lack of true clinical meaningfulness. Combined with its failure to enhance global cognition and an increased ARIA risk, routine clinical use is not supported.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/brb3.71643","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T05:45:52Z","timestamp":1786945552000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Gantenerumab for Early Alzheimer's Disease: An Updated Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-6516-4052","authenticated-orcid":false,"given":"Muhammad Nouman","family":"Javed","sequence":"first","affiliation":[{"name":"Punjab Medical College Faisalabad Medical University  Faisalabad Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6023-5835","authenticated-orcid":false,"given":"Saim 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