Serum neurofilament light chain and disease-modifying treatment as predictors of cognitive decline in multiple...

Cognitive impairment (CI) is a prevalent and early problem in multiple sclerosis (MS). Its detection and monitoring might help prevent cognitive decline and potentially inform treatment decisions.

The aim of this study was to analyze the possible associations of cognitive decline and neurofilament levels, disability measures, and disease-modifying treatments (DMTs) in patients with MS (PwMS).

64 PwMS and 14 healthy controls participated in this prospective study. Neurofilament light chain (NfL) levels were measured in the cerebrospinal fluid (CSF) samples of PwMS and serum samples of both groups. Serum samples, cognitive testing using Brief International Cognitive Assessment for MS (BICAMS) battery and disability assessment using EDSS, Nine-Hole Peg Test (9HPT) and Timed 25-Foot Walk Test (T25FWT) were evaluated at the time of diagnosis and at follow-up at 12 months. Longitudinal change in BICAMS subtest scores was calculated and its associations with NfL concentration, disability measures and demographic/clinical data were analyzed.

All PwMS were diagnosed with relapsing MS and 78.1% were started on platform DMTs, while the rest were prescribed higher-efficacy DMTs. PwMS had significantly higher sNfL concentration at baseline (11.95 vs. 5.40 pg./mL, p = 0.001) but follow-up sNfL levels were similar to those of control group (7.40 vs. 5.50 pg./mL, p = 0.768). At baseline, all BICAMS subtest scores were lower in PwMS, but the difference in the Symbol Digit Modalities Test (SDMT) was not statistically significant. However, it was the only subtest to significantly decrease at follow-up (-1.87, p = 0.024). Correlation analysis showed that SDMT1 and 2 were associated with serum NfL2 measurement. Logistic regression analysis demonstrated that serum NfL at baseline and follow-up were significant predictors for SDMT decline. Platform DMTs, when compared to higher-efficacy DMTs, also significantly increased the odds of SDMT decline.

Our findings highlight the potential of serum NfL as a marker of early IPS decline. Treatment with higher-efficacy DMTs early after diagnosis may be protective against early cognitive decline in MS.