{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T22:22:10Z","timestamp":1791843730976,"version":"4.3.4"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>We aim to investigate cognitive phenotype distribution and MRI correlates across pediatric\u2010, elderly\u2010, and adult\u2010onset MS patients as a function of disease duration.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this cross\u2010sectional study, we enrolled 1262 MS patients and 238 healthy controls, with neurological and cognitive assessments. A subset of 222 MS patients and 92 controls underwent 3T\u2010MRI scan for brain atrophy and lesion analysis. Multinomial probabilistic models identified likelihood of belonging to cognitive phenotypes (\u201cpreserved\u2010cognition,\u201d \u201cmild verbal memory\/semantic fluency,\u201d \u201cmild multi\u2010domain,\u201d \u201csevere attention\/executive,\u201d and \u201csevere multi\u2010domain\u201d) and experiencing MRI abnormalities based on disease duration and age at onset.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In all groups, the likelihood of \u201cpreserved\u2010cognition\u201d phenotype decreased, whereas \u201cmild multi\u2010domain\u201d increased with longer disease duration. In pediatric\u2010 and adult\u2010onset patients, the likelihood of \u201cmild verbal memory\/semantic fluency\u201d phenotypes decreased with longer disease duration, and that of \u201csevere multi\u2010domain\u201d increased with longer disease duration. Only in adult\u2010onset patients, the likelihood of \u201csevere executive\/attention\u201d phenotype increased with longer disease duration. All groups displayed escalating probabilities of cortical, thalamic, hippocampal, and deep gray matter atrophy over disease course. Compared to adult, pediatric\u2010onset patients showed lower probability of experiencing thalamic atrophy with longer disease duration, while elderly\u2010onset showed higher probability of experiencing cortical and hippocampal atrophy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Age at MS onset significantly influences the distribution of cognitive phenotypes and the patterns of regional gray matter atrophy throughout the disease course.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52291","type":"journal-article","created":{"date-parts":[[2025,1,25]],"date-time":"2025-01-25T06:38:01Z","timestamp":1737787081000},"page":"512-522","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Pediatric, adult, and late onset multiple sclerosis: Cognitive phenotypes and gray matter atrophy"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5531-1111","authenticated-orcid":false,"given":"Ermelinda","family":"De Meo","sequence":"first","affiliation":[{"name":"Department of Neuroinflammation, Institute of Neurology Univeristy College of London  London UK"},{"name":"NEUROFARBA Department, Neurosciences Section University of Florence  Florence Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9662-1762","authenticated-orcid":false,"given":"Emilio","family":"Portaccio","sequence":"additional","affiliation":[{"name":"NEUROFARBA Department, Neurosciences Section University of Florence  Florence Italy"},{"name":"Azienda Ospedaliera Universitaria Careggi  Florence 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