Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: A longitudinal retrospective 5-year study

Background: A limited number of studies investigated associations between serum neurofilament light chain (sNfL) and cognition in persons with multiple sclerosis (PwMS). Objective: To assess cross-sectional and longitudinal associations between sNfL levels, clinical, and cognitive performance in PwMS and age-matched healthy controls (HCs). Materials: One hundred twenty-seven PwMS (85 relapsing–remitting MS/42 progressive MS), 20 clinically isolated syndrome patients, and 52 HCs were followed for 5 years. sNfL levels were measured using the single-molecule array (Simoa) assay and quantified in picograms per milliliter. Expanded Disability Status Scale (EDSS), walking, and manual dexterity tests were obtained. At follow-up, Brief International Cognitive Assessment for MS (BICAMS) was utilized. Cognitively impaired (CI) status was derived using HC-based z-scores. Age-, sex-, and education-adjusted analysis of covariance (ANCOVA) and regression models were used. Multiple comparison–adjusted values of q < 0.05 were considered significant. Results: In PwMS, sNfL levels were cross-sectionally associated with walking speed (r = 0.235, q = 0.036), manual dexterity (r = 0.337, q = 0.002), and cognitive processing speed (CPS; r =−0.265, q = 0.012). Baseline sNfL levels predicted 5-year EDSS scores (r = 0.25, q = 0.012), dexterity (r = 0.224, q = 0.033), and CPS (r =−0.205, q = 0.049). CI patients had higher sNfL levels (27.2 vs. 20.6, p = 0.016) and greater absolute longitudinal sNfL increase when compared with non-CI patients (4.8 vs. 0.7, p = 0.04). Conclusion: Higher sNfL levels are associated with poorer current and future clinical and cognitive performance.