{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:14:37Z","timestamp":1788146077636,"version":"build-2803163510"},"reference-count":67,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T00:00:00Z","timestamp":1778457600000},"content-version":"vor","delay-in-days":40,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007013","name":"F. Hoffmann-La Roche","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007013","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["A&amp;amp;D Transl Res &amp;amp; Clin Interv"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) heterogeneity poses significant challenges for drug development, identification of individuals at risk, and treatment response prediction. Scientists have leveraged graph theory and resting\u2010state functional magnetic resonance imaging (rs\u2010fMRI) to successfully stratify people with AD. Still, the prognostic value of rs\u2010fMRI graph metrics in AD clinical trials remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We analyzed rs\u2010fMRI from participants in amyloid\u2010lowering clinical trials. Four graph metrics\u2014global efficiency, clustering coefficient, modularity, and shortest path length\u2014were computed and baseline clusters defined using unsupervised k\u2011means. We investigated the baseline connectome of each cluster to assess the level of network dysfunction and impairment (i.e., loss of global integration, resulting in disrupted communication between brain regions and reduced global efficiency). These clusters were related to a 116\u2010week change in cognition and brain volume using covariate\u2010adjusted mixed\u2010effects models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Three clusters emerged with distinct functional connectome efficiency, demographic, and AD\u2010related biomarkers profiles. These baseline differences led to significant variations in disease progression. The most impaired\u2011connectome cluster declined fastest, whereas the most integrated declined slowest.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>rs\u2010fMRI graph metrics might effectively stratify participants with AD in clinical trials and serve as potential prognostic biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/trc2.70259","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T04:10:31Z","timestamp":1778559031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional connectome metrics reveal distinct prognostic subtypes in two Phase 3 gantenerumab trials"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2115-3116","authenticated-orcid":false,"given":"Susanna","family":"Gobbi","sequence":"first","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Silvestri","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers  Basel Switzerland"},{"name":"A4P Consulting Ltd.  Sandwich UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Tonietto","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory","family":"Klein","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn","family":"van den Heuvel","sequence":"additional","affiliation":[{"name":"Center for Neurogenomics and Cognitive Research (CNCR) Vrije Universiteit and Amsterdam University Medical Center  Amsterdam Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Magon","sequence":"additional","affiliation":[{"name":"Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Biomarkers  Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,11]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410300410"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.09.001"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-021-00529-1"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583-019-0177-6"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-83739-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-021-02497-0"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01309-6"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2022.02.001"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopsych.2022.06.019"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-230561"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.02.07.23285572"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-01055-y"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tjpad.2025.100446"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.70905"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-65846-z"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1101\/2024.03.27.24304966"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/13825585.2022.2163973"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab114"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2304430"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2015.09.009"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/alz.14414"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0184661"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nicl.2013.10.015"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2016.08.005"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41592-018-0235-4"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1162\/imag_a_00257"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2009.10.003"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-48781-5"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.87.198701"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.71.065103"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.76.026107"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1162\/NECO_a_00914"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088669"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1088\/1742-5468\/2008\/10\/P10008"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.74.016110"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevE.80.016109"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1209\/0295-5075\/86\/28004"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2011.03.069"},{"key":"e_1_2_7_41_1","unstructured":"The R Project for Statistical Computing. 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