{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T14:34:19Z","timestamp":1791815659488,"version":"4.3.4"},"reference-count":50,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":4,"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":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp; Dementia"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>The temporal sequence of clinical, imaging, and biological changes in sporadic frontotemporal lobar degeneration (FTLD)\u2013associated syndromes remains poorly characterized, and a comprehensive biomarker cascade model is lacking.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>We developed a data\u2010driven biomarker cascade model in 489 patients across the FTLD spectrum (211 behaviorial variant frontotemporal dementia [bvFTD], 129 primary progressive aphasia [PPA], 71 corticobasal syndrome [CBS], 66 progressive supranuclear palsy [PSP], and 12 FTD associated with amyotrophic lateral sclerosis [FTD\u2010ALS]; 1904 patient\u2010visit observations). Plasma, magnetic resonance imaging (MRI), and clinical biomarkers were modeled using sigmoid trajectories fitted to covariate\u2010adjusted longitudinal data.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Plasma glial fibrillary acidic protein departed from normality earliest, followed by Trail Making Test Part B (TMT\u2010B), white matter lesion volume, and neurofilament light chain. Insular atrophy showed the steepest transition among MRI measures; clinical dementia rating dementia staging instrument plus National Alzheimer's Coordinating Center behavior and language domains sum of boxes declined most steeply overall. TMT\u2010B inflected earliest in bvFTD, whereas insula atrophy dominated in PPA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>This first data\u2010driven temporal cascade of multimodal biomarkers in sporadic FTLD\u2010associated syndromes offers a framework for disease staging and stage\u2010specific clinical trial design.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71722","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T11:20:16Z","timestamp":1785928816000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Temporal order of clinical, imaging, and biomarker changes in frontotemporal lobar degeneration\u2013associated syndromes"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8703-6940","authenticated-orcid":false,"given":"Alberto","family":"Benussi","sequence":"first","affiliation":[{"name":"Neurology Unit Department of Medical, Surgical and Health Sciences University of Trieste  Trieste Italy"},{"name":"Neurology Unit Hospital Care Department of Medicine Azienda Sanitaria Universitaria Giuliano Isontina  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Bracca","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"},{"name":"Department of Molecular and Translational Medicine University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Premi","sequence":"additional","affiliation":[{"name":"Stroke Unit Azienda Socio Sanitaria Territoriale (ASST) Spedali Civili  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Cantoni","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Sciences University of Brescia  Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica","family":"Palacino","sequence":"additional","affiliation":[{"name":"Neurology Unit Department of Medical, Surgical and Health Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aurora","family":"Saccavini","sequence":"additional","affiliation":[{"name":"Neurology Unit Department of Medical, Surgical and Health Sciences University of Trieste  Trieste Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Sofia","family":"Cotelli","sequence":"additional","affiliation":[{"name":"Department of Continuity of Care and Frailty ASST Spedali Civili of Brescia  Brescia 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J","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"King's College London  London UK"},{"name":"NIHR Maudsley Biomedical Research Centre  London UK"},{"name":"Banner Sun Health Research Institute  Sun City Arizona USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry Institute of Neuroscience and Physiology the Sahlgrenska Academy at the University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"},{"name":"Department of Pathology and Laboratory Medicine University of Wisconsin School of Medicine and Public Health  Madison Wisconsin USA"},{"name":"Wisconsin Alzheimer's Disease 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