{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:09:34Z","timestamp":1779358174691,"version":"3.51.4"},"reference-count":35,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T00:00:00Z","timestamp":1771804800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"ECTRIMS-MAGNIMS"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Mult Scler"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) onset occurs at diverse ages. Age of onset impact on clinical, brain MRI, and cognitive profiles remains unclear. We investigated the substrates of Symbol Digit Modalities Test (SDMT) impairment in patients with late-onset MS (LOMS) (\u2a7e45\u2009years) compared to adult-onset MS (AOMS) (&lt;45\u2009years).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>294 AOMS and 80 LOMS patients with disease duration of maximum 6 years from symptom onset and 519 healthy controls were retrospectively included from a multicenter MAGNIMS data set. We assessed between-group differences and correlates of SDMT impairment measuring lesion volume (LV), atrophy, global, intra- and inter-hemispheric structural connectivity and disconnection indices.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      38% LOMS were impaired on SDMT compared to 39% AOMS (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.751). LOMS showed higher LV (FDR-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.018), gray matter (GM) atrophy (FDR-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.050), intra- and inter-hemispheric disconnection compared to AOMS (all FDR-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.028). Furthermore, LOMS showed higher modularity (FDR-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.018) and decreased density (FDR-\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.001). Substrates of SDMT impairment were intra-hemispheric disconnection, LV, clustering coefficient, mean strength and efficiency (AUC\u2009=\u20090.730) in AOMS and commissural ratio and GM atrophy (AUC\u2009=\u20090.760) in LOMS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>Substrates contributing to SDMT impairment differ between these two distinct cohorts, being primarily driven by network dysfunction in AOMS and neurodegenerative processes in LOMS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13524585261417265","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T14:30:51Z","timestamp":1771857051000},"page":"289-301","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and MRI substrates of Symbol Digit Modalities Test impairment in multiple sclerosis patients with an adult- and late-onset"],"prefix":"10.1177","volume":"32","author":[{"given":"Antonia L","family":"Wenger","sequence":"first","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neuropsychology and Behavioral Neurology Unit, Interdisciplinary Platform Psychiatry and Psychology, Division of Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Pagani","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8189-0452","authenticated-orcid":false,"given":"Alessandro","family":"Meani","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7826-0019","authenticated-orcid":false,"given":"Paolo","family":"Preziosa","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Gallo","sequence":"additional","affiliation":[{"name":"Department of Advanced Medical and Surgical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabeth","family":"Solana","sequence":"additional","affiliation":[{"name":"Neuroimmunology and MS Unit, Laboratory of Advanced Imaging in Neuroimmunological Diseases, Hospital Clinic Barcelona, Institut d\u2019investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) and Universitat de Barcelona, Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2504-6959","authenticated-orcid":false,"given":"Menno M","family":"Schoonheim","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Neurosciences, MS Center Amsterdam, Amsterdam Neuroscience, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Enzinger","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Graz, Graz, Austria; Division of Neuroradiology, Vascular and Interventional Radiology, Department of Radiology, Medical University of Graz, Graz, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergiu","family":"Groppa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Focus Program Translational Neuroscience (FTN) and Immunotherapy (FZI), Rhine-Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University, Mainz, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario A","family":"Ocampo-Pineda","sequence":"additional","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7703-0553","authenticated-orcid":false,"given":"Alessandro","family":"Cagol","sequence":"additional","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Dipartimento di Scienze della Salute, Universit\u00e0 degli Studi di Genova, Genova, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4910-1414","authenticated-orcid":false,"given":"Matthias","family":"Weigel","sequence":"additional","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland; Division of Radiological Physics, Department of Radiology, University Hospital Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Calabrese","sequence":"additional","affiliation":[{"name":"Neuropsychology and Behavioral Neurology Unit, Interdisciplinary Platform Psychiatry and Psychology, Division of Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4175-5509","authenticated-orcid":false,"given":"Ludwig","family":"Kappos","sequence":"additional","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4917-8761","authenticated-orcid":false,"given":"Cristina","family":"Granziera","sequence":"additional","affiliation":[{"name":"Translational Imaging in Neurology (ThINk) Basel, Department of Biomedical Engineering, University Hospital Basel and University of Basel, Basel, Switzerland; Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), University Hospital Basel and University of Basel, Basel, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-0479","authenticated-orcid":false,"given":"Massimo","family":"Filippi","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy; Neurorehabilitation Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurophysiology Service, IRCCS San Raffaele Scientific Institute, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2358-4320","authenticated-orcid":false,"given":"Maria A","family":"Rocca","sequence":"additional","affiliation":[{"name":"Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy; Neurology Unit, IRCCS San Raffaele Scientific Institute, Milan, Italy; Vita-Salute San Raffaele University, Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,2,23]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102588"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2021.102816"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines7010022"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10072-010-0370-x"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2018.00238"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1177\/13524585211039112"},{"key":"e_1_3_3_8_2","article-title":"Molecular mechanisms of immunosenescene and inflammaging: Relevance to the immunopathogenesis and treatment of multiple sclerosis","volume":"12","author":"Perdaens O","year":"2021","unstructured":"Perdaens O, Van Pesch V. 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