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However, the single use of these markers do only partially explain the large heterogeneity found in PwMS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To investigate the use of multimodal (bio)markers: i.e., serum and cerebrospinal fluid (CSF) levels of neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) and conventional imaging markers in predicting cognitive functioning in PwMS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Eighty-two PwMS (56 females, disease duration\u2009=\u200914\u2009\u00b1\u20099\u00a0years) underwent neuropsychological and neurological examination, structural magnetic resonance imaging, blood sampling and lumbar puncture. PwMS were classified as cognitively impaired (CI) if scoring\u2009\u2265\u20091.5SD below normative scores on\u2009\u2265\u200920% of test scores. Otherwise, PwMS were defined as cognitively preserved (CP). Association between fluid and imaging (bio)markers were investigated, as well as binary logistics regression to predict cognitive status. Finally, a multimodal marker was calculated using statistically important predictors of cognitive status.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Only higher NfL levels (in serum and CSF) correlated with worse processing speed (<jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.286, <jats:italic>p<\/jats:italic>\u2009=\u20090.012 and <jats:italic>r<\/jats:italic>\u2009=\u2009\u2212\u20090.364, <jats:italic>p<\/jats:italic>\u2009=\u20090.007, respectively). sNfL added unique variance in the prediction of cognitive status on top of grey matter volume (NGMV), <jats:italic>p<\/jats:italic>\u2009=\u20090.002). A multimodal marker of NGMV and sNfL yielded most promising results in predicting cognitive status (sensitivity\u2009=\u200985%, specificity\u2009=\u200958%).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Fluid and imaging (bio)markers reflect different aspects of neurodegeneration and cannot be used interchangeably as markers for cognitive functioning in PwMS. The use of a multimodal marker, i.e., the combination of grey matter volume and sNfL, seems most promising for detecting cognitive deficits in MS.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-023-11676-4","type":"journal-article","created":{"date-parts":[[2023,4,27]],"date-time":"2023-04-27T03:30:33Z","timestamp":1682566233000},"page":"3851-3861","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["A multimodal marker for cognitive functioning in multiple sclerosis: the role of NfL, GFAP and conventional MRI in predicting cognitive functioning in a prospective clinical cohort"],"prefix":"10.1007","volume":"270","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4639-5138","authenticated-orcid":false,"given":"Maureen","family":"van Dam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigit A.","family":"de Jong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eline A. 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I.M.N. is supported by the Dutch MS Research Foundation, grant nr. 15-911. M.H. is supported by the Dutch MS Research Foundation, grant nr. 16-954b. J.J.G.G. has served as a consultant for or received research support from Biogen, Celgene, Genzyme, MedDay, Merck, Novartis and Teva. B.M.J.U. reports personal fees for consultancies from Biogen Idec, Genzyme, Merck Serono, Novartis, Roche, and Teva, outside the submitted work. C.E.T. has a collaboration contract with ADx Neurosciences and Quanterix, performed contract research or received grants from AC-Immune, Axon Neurosciences, Biogen, BioOrchestra, Brainstorm Therapeutics, Celgene, EIP Pharma, Eisai, Grifols, Novo Nordisk, PeopleBio, Quanterix, Roche, Toyama, Vivoryon. She serves on editorial boards of Alzheimer Research and Therapy, and Neurology. H.E.H. serves on the editorial board of Multiple Sclerosis Journal, receives research support from the Dutch MS Research Foundation and the Dutch Research Council. She has served as a consultant for or received research support from Atara Biotherapeutics, Biogen, Novartis, Celgene\/Bristol Meyers Squibb, Sanofi Genzyme, MedDay and Merck BV. B.A.d.J., E.A.W., M.K., B.M., and S.d.G.D. report no disclosures relevant to the manuscript.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"The Medical Ethics Research Committee of Amsterdam UMC concluded that the Medical Research Involving Human Subjects Act (WMO) did not apply to this study, as the data collection was part of clinical care (number METC-2016.395).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical standards statement"}}]}}