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We investigated cross\u2010sectional associations between magnetic resonance imaging (MRI)\u2013derived brain volumes and the presence of cognitive impairment outcomes five years after the first presentation with a demyelinating event.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Comprehensive cognitive assessments were performed five years after a first clinical demyelinating presentation using the Minimal Assessment of Cognitive Function in MS (MACFIMS). Participant\n                      <jats:italic>Z<\/jats:italic>\n                      scores were calculated for each MACFIMS subtest using available regression\u2010based normative data. Participants were defined as having a cognitive outcome if one or more MACFIMS subtests were below the applied cutoff of\n                      <jats:italic>Z<\/jats:italic>\n                      \u2009\u2264\u2009\u22121.50. Gray matter volumes (GMV) were calculated using 3D T1\u2010weighted MRI sequences. Logistic regression models assessed associations between 5\u2010year MRI measures and cognitive impairment (adjusting for total intracranial volume where relevant).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Forty participants were recruited. Lower GMV at 5\u2009years was associated with 5\u2010year cognitive impairment outcomes (OR\u2009=\u20091.06 per 1 cm\n                      <jats:sup>3<\/jats:sup>\n                      decrease in GMV, 95% CI [1.00\u20131.13],\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.044). Among participants with a cognitive impairment outcome, there were significant associations between lower GMV and advancing age (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0095). Exploratory analysis of estimated marginal contrasts suggested that cognitive impairment outcomes were potentially associated with GMV above the age of 39\u2009years (\n                      <jats:italic>Z<\/jats:italic>\n                      \u2009\u2264\u2009\u22121.50:\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0476).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Five years after a first demyelinating event, GMV volumes on MRI are significantly associated with the presence of cognitive outcomes, while advancing age also appears to be associated with GMV and cognitive outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70385","type":"journal-article","created":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T08:50:06Z","timestamp":1775811006000},"page":"2124-2133","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advancing Age Modulates Associations Between Cognitive Impairment and Brain Volumes in Early\n                    <scp>MS<\/scp>"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4360-8991","authenticated-orcid":false,"given":"Piriyankan","family":"Ananthavarathan","sequence":"first","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8093-4548","authenticated-orcid":false,"given":"Marco","family":"Pitteri","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"},{"name":"National Hospital for Neurology and Neurosurgery, Department of Neuropsychology  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7201-7475","authenticated-orcid":false,"given":"Michael","family":"Foster","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1506-8983","authenticated-orcid":false,"given":"Sara","family":"Collorone","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2380-8152","authenticated-orcid":false,"given":"Sara","family":"Salama","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"},{"name":"Department of Neurology, Faculty of Medicine University of Alexandria  Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Colato","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferran","family":"Prados","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"},{"name":"Department of Medical Physics and Biomedical Engineering Faculty of Engineering Science, UCL Hawkes Institute, University College London  London UK"},{"name":"Universitat Oberta de Catalunya, e\u2010Health Centre  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2443-8800","authenticated-orcid":false,"given":"Baris","family":"Kanber","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"},{"name":"Department of Medical Physics and Biomedical Engineering Faculty of Engineering Science, UCL Hawkes Institute, University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marios","family":"Yiannakas","sequence":"additional","affiliation":[{"name":"Queen Square Institute of Neurology, Queen Square MS Centre, Department of Neuroinflammation University College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia A. 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