Brain-derived neurotrophic factor and neurofilament light chain in cerebrospinal fluid are inversely correlated with cognition in Multiple Sclerosis at the time of diagnosis

Background: Cognitive performance may be impaired in MS even at the earliest stages of disease. We tested whether brain-derived neurotrophic factor and neurofilament light chain levels in serum and cerebrospinal fluid (CSF) samples (sNfL/cNfL/sBDNF/cBDNF) collected at the time of diagnosis are associated with cognitive performance.

Methods: We measured sNfL/cNfL/sBDNF/cBDNF using single-molecule array (Simoa) in 47 newly diagnosed patients (32 relapsing-remitting MS/6 primary progressive MS/9 clinically isolated syndrome). Partial correlations between average z-score on neuropsychological tests and sNfL/sBDNF/cNfL/cBDNF were computed after adjusting for covariates. Multivariate analysis of covariance determined the effect of cognitive status on biomarker levels. A composite measure of NfL and BDNF was submitted to similar exploratory analysis.

Results: Cognitive performance correlated inversely with cNfL (r=-0.451/q=0.032) and cBDNF (r=-0.406/q=0.034). Impairment in at least two different tests was linked to higher cNfL (p=0.011) and cBDNF (p=0.035) levels compared to impairment in only one test and for cNfL also compared to no impairment at all (p=0.01). Composite CSF biomarker measure accounting for both cNfL and cBDNF correlated more strongly with tests of information processing (p=0.048) and verbal learning/memory consolidation (p = 0.02) as compared to the single CSF biomarkers.

Conclusions: CSF BDNF and NfL levels measured at the time of diagnosis are inversely associated with cognitive performance in MS. Our findings suggest that CSF biomarkers linked to different pathophysiological processes reflect neuropsychological impairment in the earliest stages of the disease. Combining different CSF measures might facilitate the developing of a better biomarker of cognition in MS.