{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T03:42:31Z","timestamp":1788838951546,"version":"build-2803163510"},"reference-count":56,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T00:00:00Z","timestamp":1735257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","award":["09150172010056"],"award-info":[{"award-number":["09150172010056"]}],"id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the interrelationship between cortical lesions and cortical thinning and volume loss in people with multiple sclerosis within cortical networks, and how this relates to future cognition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this longitudinal study, 230 people with multiple sclerosis and 60 healthy controls underwent 3 Tesla MRI at baseline and neuropsychological assessment at baseline and 5\u2010year follow\u2010up. Cortical regions (<jats:italic>N<\/jats:italic>\u2009=\u2009212) were divided into seven functional networks. Regions were defined as either lesional or normal\u2010appearing cortex based on presence of a cortical lesion on artificial intelligence\u2010generated double inversion\u2010recovery scans. Cortical volume and thickness were determined within lesional or normal\u2010appearing cortex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Prevalence of at least one cortical lesion was highest in the limbic (73%) followed by the default mode network (70.9%). Multiple sclerosis\u2010related cortical thinning was more pronounced in lesional (mean <jats:italic>Z<\/jats:italic>\u2010score\u2009=\u20090.70\u2009\u00b1\u20090.84) compared to normal\u2010appearing cortex (\u22120.45\u2009\u00b1\u20090.60; <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) in all, except sensorimotor, networks. Cognitive dysfunction, particularly of verbal memory, visuospatial memory, and inhibition, at follow\u2010up was best predicted by baseline network volume of normal\u2010appearing cortex of the default mode network [<jats:italic>B<\/jats:italic> (95% CI)\u2009=\u20090.31 (0.18; 0.43), <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001]. Mediation analysis showed that the effect of cortical lesions on future cognition was mediated by volume loss of the normal\u2010appearing instead of lesional cortex, independent of white matter lesion volume.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Multiple sclerosis\u2010related cortical thinning was worse in lesional compared to normal\u2010appearing cortex, while volume loss of normal\u2010appearing cortex was most predictive of subsequent cognitive decline, particularly in the default mode network. Mediation analyses indicate that cortical lesions impact cognitive decline plausibly by inducing atrophy, rather than through a direct effect.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.52261","type":"journal-article","created":{"date-parts":[[2024,12,27]],"date-time":"2024-12-27T21:40:21Z","timestamp":1735335621000},"page":"121-136","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cortical lesions impact cognitive decline in multiple sclerosis via volume loss of nonlesional cortex"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3628-4127","authenticated-orcid":false,"given":"Eva A.","family":"Krijnen","sequence":"first","affiliation":[{"name":"MS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Department of Neurology Massachusetts General Hospital, Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"van Dam","sequence":"additional","affiliation":[{"name":"MS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Institute of Psychology, Department of Health, Medical and Neuropsychology Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albulena","family":"Bajrami","sequence":"additional","affiliation":[{"name":"MS Center Amsterdam, Department of Anatomy and Neurosciences, Amsterdam Neuroscience Vrije Universiteit Amsterdam  Amsterdam The Netherlands"},{"name":"Division of Neurology, Department of Emergency \u201cS. 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