{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T04:45:42Z","timestamp":1782449142350,"version":"3.54.5"},"reference-count":37,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Institute for Translational and Intersectoral Health Care Research (INTIVA), Germany"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ther Adv Neurol Disord"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Multiple sclerosis (MS) is influenced by age-related brain alterations and affects cellular aging mechanisms. Machine-learning models can estimate brain-predicted age from magnetic resonance imaging (MRI) to quantify these aging-related changes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives:<\/jats:title>\n                    <jats:p>This study examines whether the difference between predicted and chronological age (BrainAGE) relates to clinical disability and biomarkers of neuro-axonal injury in MS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design:<\/jats:title>\n                    <jats:p>This study analyzed brain-predicted age from structural 3D T1-weighted MRI in 82 patients with relapsing MS enrolled in three prospective clinical trials and 30 healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>BrainAGE, calculated as MRI-predicted minus chronological age, was correlated with the Expanded Disability Status Scale (EDSS), MS Functional Composite subtests, and serum neurofilament light chain and glial fibrillary acidic protein.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The mean chronological age of patients and healthy controls included in this study was 39.2 and 40.9\u2009years, respectively. Patients with MS (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200982) showed a higher BrainAGE (6.48\u2009\u00b1\u20096.83\u2009years) than controls (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2009=\u200930; 0.69\u2009\u00b1\u20096.5\u2009years;\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.0002). BrainAGE increased stepwise from controls to patients with EDSS\u2009&lt;\u20093 and EDSS \u2a7e3 (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). Higher BrainAGE correlated with worse 9-Hole Peg Test (9HPT, \u03c1\u2009=\u20090.34,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.002) and Timed 25-Foot Walk performance (T25FW, \u03c1\u2009=\u20090.23,\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.043), but not with serum neurofilament light chain (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.68) or glial fibrillary acidic protein (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009=\u20090.33). In multivariable regression models adjusting for chronological age, sex, disease duration, and disease-modifying therapy, BrainAGE remained significantly associated with EDSS, 9HPT, and T25FW performance. sNfL and sGFAP remained nonsignificant after adjustment.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Our findings suggest that BrainAGE and serum biomarkers capture complementary aspects of MS pathology, supporting a multimodal approach to assess disease progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration:<\/jats:title>\n                    <jats:p>ClinicalTrials.gov ID: SATURATE: NCT05701423, 360PMS: NCT06501950, SAFEGUIDE-MS: NCT06461481.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/17562864261458516","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T09:22:09Z","timestamp":1782206529000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Brain age gap in multiple sclerosis: associated with disability but independent of serum biomarkers"],"prefix":"10.1177","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3080-2277","authenticated-orcid":false,"given":"Marc","family":"Pawlitzki","sequence":"first","affiliation":[{"name":"Department of Neurology, Heinrich-Heine University Duesseldorf, Moorenstra\u00dfe 5, Duesseldorf 40225, Germany"},{"name":"Department of Neurology, Medical Faculty University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0835-0120","authenticated-orcid":false,"given":"Patricia","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-1415","authenticated-orcid":false,"given":"Lars","family":"Masanneck","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"},{"name":"Hasso Plattner Institute, University of Potsdam, Potsdam, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Hagler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Meier","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty University Hospital D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marius","family":"Vach","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hernan","family":"Inojosa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8799-8202","authenticated-orcid":false,"given":"Tjalf","family":"Ziemssen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Center of Clinical Neuroscience, University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivien Lorena","family":"Ivan","sequence":"additional","affiliation":[{"name":"Department of Diagnostic and Interventional Radiology, Medical Faculty and University Hospital D\u00fcsseldorf, Heinrich-Heine-University D\u00fcsseldorf, D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shammi","family":"More","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Medicine, Brain &amp; Behaviour (INM-7), Research Centre J\u00fclich, J\u00fclich, Germany"},{"name":"Institute of Systems 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