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

Mult Scler. 2020 Nov;26(13):1670-1681. doi: 10.1177/1352458519881428. Epub 2019 Oct 15.


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.

Keywords: Multiple sclerosis (MS); cognition; longitudinal; neurofilament light chain; processing speed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers
  • Cognition
  • Cross-Sectional Studies
  • Humans
  • Intermediate Filaments
  • Multiple Sclerosis* / complications
  • Multiple Sclerosis* / diagnostic imaging
  • Neurofilament Proteins
  • Retrospective Studies


  • Biomarkers
  • Neurofilament Proteins