The weak association between neurofilament levels at multiple sclerosis onset and cognitive performance after 9 years

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 Spearmans 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.