BACKGROUND: Neurofilament light chain level in serum (sNfL) and cerebrospinal fluid (CSF-NfL) is a promising biomarker of disease activity in multiple sclerosis (MS). However, predictive value of neurofilaments for development of cognitive decline over long-term follow-up has not been extensively studied. OBJECTIVE: To investigate the relationship between early neurofilament levels and cognitive performance after 9-years. METHODS: We included 58 MS patients from the SET study. sNfL levels were measured at screening, at 1 and 2 years. CSF-NfL were measured in 36 patients at screening. Cognitive performance was assessed by the Brief International Cognitive Assessment for Multiple Sclerosis and the Paced Auditory Serial Addition Test-3 s at baseline, at 1, 2 and 9 years. Association between neurofilament levels and cognition was analyzed using Spearman´s correlation, logistic regression and mixed models. RESULTS: We did not observe associations among early sNfL levels and cross-sectional or longitudinal cognitive measures, except of a trend for association between higher sNfL levels at screening and lower California Verbal Learning Test-II (CVLT-II) scores at year 1 (rho=-0.31, unadjusted p = 0.028). Higher sNfL level was not associated with increased risk of cognitive decline, except of a trend for greater risk of CVLT-II decrease in patients with higher sNfL levels at 1 year (OR=15.8; 95% CI=1.7-147.0; unadjusted p = 0.015). Similar trends were observed for CSF-NfL. CONCLUSION: We found only weak association between sNfL levels at disease onset and evolution of cognitive performance over long-term follow-up.

Department of Neurology and Center of Clinical Neuroscience 1st Faculty of Medicine Charles University and General University Hospital Katerinska 30 120 00 Prague Czech Republic

Department of Neurology University at Buffalo Buffalo NY United States

Departments of Medicine Clinical Research Biomedicine and Biomedical Engineering Neurologic Clinic and Policlinic University Hospital and University of Basel Switzerland

Institute of Medical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

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