Neurofilament Light Chain and Disability Measures as Predictors of Cognitive Decline in Early Multiple Sclerosis

BACKGROUND This study investigated whether cerebrospinal fluid (CSF) and serum neurofilament light chain (NfL), a biomarker of axonal degeneration, combined with manual dexterity and ambulation measures, can serve as reliable predictors of MS-related cognitive impairment (CI). MATERIAL AND METHODS A total of 99 newly diagnosed patients with MS (PwMS) and 37 healthy controls (control group [CG]) were included in the study. Serum NfL levels were measured in both groups, whereas PwMS also underwent CSF NfL analysis. Cognition was assessed using the Brief International Cognitive Assessment for MS (BICAMS) test battery. Disability was evaluated using the Expanded Disability Status Scale (EDSS), Nine-Hole Peg Test (NHPT), and Timed 25-Foot Walk Test (T25FWT). PwMS were classified as cognitively impaired if Z-scores of 1 or more BICAMS tests were below -1.5 standard deviations from the mean of the CG scores. RESULTS PwMS had significantly lower median scores in the Brief Visuospatial Memory and Learning Revised (BVMT-R) and California Verbal Learning Test II (CVLT) (p=0.003 and p<0.001, respectively). They had significantly longer NHPT and T25FWT times (p<0.001) and higher serum NfL concentrations (11.8 vs 5.8 pg/mL, p<0.001). CI was identified in 32.3% of PwMS. Linear regression showed that lower CSF NfL levels significantly predicted higher BVMT-R scores. Logistic regression analysis demonstrated that NHPT and T25FWT times significantly predicted impairment in SDMT and BVMT-R. Serum NfL concentration showed a tendency toward predicting SDMT impairment (p=0.051), whereas CSF NfL levels significantly predicted abnormal BVMT-R scores and overall CI. CONCLUSIONS In early-stage MS, CSF and serum NfL concentrations, along with ambulation and manual dexterity measurements, can be valuable tools for predicting cognitive impairment.