TY - JOUR
T1 - A multimodal marker for cognitive functioning in multiple sclerosis
T2 - the role of NfL, GFAP and conventional MRI in predicting cognitive functioning in a prospective clinical cohort
AU - van Dam, Maureen
AU - de Jong, Brigit A.
AU - Willemse, Eline A. J.
AU - Nauta, Ilse M.
AU - Huiskamp, Marijn
AU - Klein, Martin
AU - Moraal, Bastiaan
AU - de Geus-Driessen, Sanne
AU - Geurts, Jeroen J. G.
AU - Uitdehaag, Bernard M. J.
AU - Teunissen, Charlotte E.
AU - Hulst, Hanneke E.
N1 - Funding Information: The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: M.v.D. is supported by a research grant from BMS. 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. Publisher Copyright: © 2023, The Author(s).
PY - 2023/8
Y1 - 2023/8
N2 - Background: Cognitive impairment in people with MS (PwMS) has primarily been investigated using conventional imaging markers or fluid biomarkers of neurodegeneration separately. However, the single use of these markers do only partially explain the large heterogeneity found in PwMS. Objective: 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. Methods: Eighty-two PwMS (56 females, disease duration = 14 ± 9 years) underwent neuropsychological and neurological examination, structural magnetic resonance imaging, blood sampling and lumbar puncture. PwMS were classified as cognitively impaired (CI) if scoring ≥ 1.5SD below normative scores on ≥ 20% 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. Results: Only higher NfL levels (in serum and CSF) correlated with worse processing speed (r = − 0.286, p = 0.012 and r = − 0.364, p = 0.007, respectively). sNfL added unique variance in the prediction of cognitive status on top of grey matter volume (NGMV), p = 0.002). A multimodal marker of NGMV and sNfL yielded most promising results in predicting cognitive status (sensitivity = 85%, specificity = 58%). Conclusion: 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.
AB - Background: Cognitive impairment in people with MS (PwMS) has primarily been investigated using conventional imaging markers or fluid biomarkers of neurodegeneration separately. However, the single use of these markers do only partially explain the large heterogeneity found in PwMS. Objective: 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. Methods: Eighty-two PwMS (56 females, disease duration = 14 ± 9 years) underwent neuropsychological and neurological examination, structural magnetic resonance imaging, blood sampling and lumbar puncture. PwMS were classified as cognitively impaired (CI) if scoring ≥ 1.5SD below normative scores on ≥ 20% 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. Results: Only higher NfL levels (in serum and CSF) correlated with worse processing speed (r = − 0.286, p = 0.012 and r = − 0.364, p = 0.007, respectively). sNfL added unique variance in the prediction of cognitive status on top of grey matter volume (NGMV), p = 0.002). A multimodal marker of NGMV and sNfL yielded most promising results in predicting cognitive status (sensitivity = 85%, specificity = 58%). Conclusion: 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.
KW - CSF
KW - Cognition
KW - GFAP
KW - MRI
KW - Multiple sclerosis
KW - Neurofilament light
KW - Serum
UR - http://www.scopus.com/inward/record.url?scp=85153628385&partnerID=8YFLogxK
U2 - https://doi.org/10.1007/s00415-023-11676-4
DO - https://doi.org/10.1007/s00415-023-11676-4
M3 - Article
C2 - 37101095
SN - 0340-5354
VL - 270
SP - 3851
EP - 3861
JO - Journal of neurology
JF - Journal of neurology
IS - 8
ER -