{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T16:43:17Z","timestamp":1789922597988,"version":"4.0.1"},"reference-count":75,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T00:00:00Z","timestamp":1722470400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001673","name":"Fondation J\u00e9r\u00f4me Lejeune","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001673","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000957","name":"Alzheimer's Association","doi-asserted-by":"publisher","award":["AARG\u201022\u2010923680"],"award-info":[{"award-number":["AARG\u201022\u2010923680"]}],"id":[{"id":"10.13039\/100000957","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010805","name":"Fundaci\u00f3n Tatiana P\u00e9rez de Guzm\u00e1n el Bueno","doi-asserted-by":"publisher","award":["IIBSP\u2010DOW\u20102020\u2010151"],"award-info":[{"award-number":["IIBSP\u2010DOW\u20102020\u2010151"]}],"id":[{"id":"10.13039\/501100010805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2024,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>INTRODUCTION<\/jats:title><jats:p>In Down syndrome (DS), white matter hyperintensities (WMHs) are highly prevalent, yet their topography and association with sociodemographic data and Alzheimer's disease (AD) biomarkers remain largely unexplored.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>In 261 DS adults and 131 euploid controls, fluid\u2010attenuated inversion recovery magnetic resonance imaging scans were segmented and WMHs were extracted in concentric white matter layers and lobar regions. We tested associations with AD clinical stages, sociodemographic data, cerebrospinal fluid (CSF) AD biomarkers, and gray matter (GM) volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>In DS, total WMHs arose at age 43 and showed stronger associations with age than in controls. WMH volume increased along the AD continuum, particularly in periventricular regions, and frontal, parietal, and occipital lobes. Associations were found with CSF biomarkers and temporo\u2010parietal GM volumes.<\/jats:p><\/jats:sec><jats:sec><jats:title>DISCUSSION<\/jats:title><jats:p>WMHs increase 10 years before AD symptom onset in DS and are closely linked with AD biomarkers and neurodegeneration. This suggests a direct connection to AD pathophysiology, independent of vascular risks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Highlights<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>White matter hyperintensities (WMHs) increased 10 years before Alzheimer's disease symptom onset in Down syndrome (DS).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>WMHs were strongly associated in DS with the neurofilament light chain biomarker.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>WMHs were more associated in DS with gray matter volume in parieto\u2010temporal areas.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec>","DOI":"10.1002\/alz.14146","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T06:06:07Z","timestamp":1722492367000},"page":"6527-6541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Characterization of white matter hyperintensities in Down syndrome"],"prefix":"10.1002","volume":"20","author":[{"given":"Alejandra O.","family":"Morcillo\u2010Nieto","sequence":"first","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara E.","family":"Zsadanyi","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose E.","family":"Arriola\u2010Infante","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carmona\u2010Iragui","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana de S\u00edndrome de Down Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Montal","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"},{"name":"Barcelona Supercomputing Center  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Pegueroles","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus Rozalem","family":"Aranha","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L\u00eddia","family":"Vaqu\u00e9\u2010Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Department of Neurology Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences, University of Barcelona Barcelona, Spain. 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