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Cortical and subcortical volumes were parcellated, and serum neurofilament light chain (NfL) levels were measured. Biomarker progression was assessed with discriminative event\u2010based and regression modeling.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS<\/jats:title>\n \n Symptomatic\n GRN<\/jats:italic>\n carriers showed elevated WMHs, primarily in the frontal lobe, while no significant increase was observed in symptomatic\n C9orf72<\/jats:italic>\n or\n MAPT<\/jats:italic>\n carriers. WMH abnormalities preceded NfL elevation, ventricular enlargement, and cortical atrophy. Longitudinally, baseline WMHs predicted subcortical changes, while subcortical volumes did not predict WMH changes, suggesting WMHs may precede neurodegeneration.\n <\/jats:p>\n <\/jats:sec>\n \n DISCUSSION<\/jats:title>\n \n WMHs are elevated in a subset of\n GRN<\/jats:italic>\n \u2010associated FTD. When present, they appear early and should be considered in disease progression models.\n <\/jats:p>\n <\/jats:sec>\n \n Highlights<\/jats:title>\n \n \n \n \n Elevated WMH volumes are found predominantly in symptomatic\n GRN<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:list-item>\n \n WMH accumulation is mostly observed in the frontal lobe.<\/jats:p>\n <\/jats:list-item>\n \n \n WMH abnormalities appear early in\n GRN<\/jats:italic>\n \u2010associated FTD, before NfL, atrophy, and ventriculomegaly.\n <\/jats:p>\n <\/jats:list-item>\n \n Longitudinally, WMH volumes can predict subcortical changes, but not vice versa.<\/jats:p>\n <\/jats:list-item>\n \n \n WMHs are key early markers in\n GRN<\/jats:italic>\n \u2010associated FTD and should be included in progression models.\n <\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/alz.70695","type":"journal-article","created":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T03:16:41Z","timestamp":1759893401000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["White matter hyperintensities precede other biomarkers in\n GRN<\/i>\n frontotemporal dementia"],"prefix":"10.1002","volume":"21","author":[{"given":"Mahdie","family":"Soltaninejad","sequence":"first","affiliation":[{"name":"McConnell Brain Imaging Centre Montreal Neurological Institute McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahsa","family":"Dadar","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute Department of Psychiatry McGill University Montr\u00e9al Qu\u00e9bec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. 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