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mean diffusivity (PSMD), a sensitive diffusion magnetic resonance imaging (MRI) marker of microvascular white matter (WM) injury, in sporadic Alzheimer's disease (sAD) and Down syndrome (DS)\u2013associated AD (DSAD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHOD<\/jats:title>\n                    <jats:p>This cross\u2010sectional study included 150 euploid controls, 118 subjects with sAD, and 228 DS adults (34.65% with symptomatic AD). PSMD was derived from 3T\u2010MRI diffusion tensor imaging. Associations with sociodemographic, clinical stage, cerebrospinal fluid (CSF), and small vessel disease markers were examined.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>PSMD correlated with age in all groups, showing a stronger association in DS, with alterations apparent 15 years before the population's dementia age at onset. In euploid and DS, higher PSMD correlated with AD severity, CSF\u2010neurofilament light chain (NfL), microbleeds, and WM hyperintensities (WMH). PSMD abnormalities were more frequent than WMH, especially in DS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>PSMD is a sensitive early biomarker of WM injury across sAD and DSAD, preceding symptom onset and capturing multifactorial disease processes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.71507","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T08:51:31Z","timestamp":1780044691000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Peak width of skeletonized mean diffusivity reveals early and multifactorial white matter injury across sporadic and Down syndrome\u2013associated Alzheimer's disease"],"prefix":"10.1002","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2202-3521","authenticated-orcid":false,"given":"Alejandra O.","family":"Morcillo\u2010Nieto","sequence":"first","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1484-7132","authenticated-orcid":false,"given":"Maria","family":"Franquesa\u2010Mullerat","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2033-5989","authenticated-orcid":false,"given":"Sara E.","family":"Zsadanyi","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED)  Madrid Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3298-4601","authenticated-orcid":false,"given":"Jos\u00e9 Enrique","family":"Arriola\u2010Infante","sequence":"additional","affiliation":[{"name":"Department of Neurology Torrec\u00e1rdenas University Hospital  Almer\u00eda Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-6559","authenticated-orcid":false,"given":"L\u00eddia","family":"Vaqu\u00e9\u2010Alc\u00e1zar","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Department of Medicine, Faculty of Medicine and Health Sciences, Institute of Neurosciences University of Barcelona  Barcelona Spain"},{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS)  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mateus","family":"Rozalem\u2010Aranha","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Neuroradiology Section, Department of Radiology, Facultad de Medicina Hospital de la Santa Creu i Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Allende","family":"Parra","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, IR SANT PAU Hospital de la Santa Creu i Sant Pau  Barcelona Spain"},{"name":"Institut de Neuroci\u00e8ncies Universitat Aut\u00f2noma de 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