Neurofilament and Brain Atrophy and Their Association with Cognition in Multiple Sclerosis: A 10-Year Follow-Up Study

Abstract

Introduction. Cognitive impairment is an important contributor to disability in multiple sclerosis (MS). Disconnection of neuronal circuits due to axonal injury is probably an important underlying mechanism for this disability. Neurofilament light chain (NfL) is a neuron-specific constituent of axons and has gained increasing attention as a biomarker of axonal injury. Objective. To assess the association between NfL in serum (sNfL) and cerebrospinal fluid (cNfL) and cognitive function over 10 years and compare these associations with volumetric brain magnetic resonance imaging (MRI) measurements. Methods. Newly diagnosed MS patients were followed prospectively with baseline NfL and MRI as well as with clinical and cognitive assessments for up to 10 years. Results. Forty-one patients were included. Baseline sNfL correlated negatively with symbol digit modalities test (SDMT) at baseline ($r=-0.45$, $p=0.005$), year 5 ($r=-0.41$, $p=0.017$), and at year 10 ($r=-0.52$, $p=0.008$). Baseline cNfL correlated with baseline SDMT ($r=-0.34$, $p=0.030$) and SDMT at year 10 ($r=-0.44$, $p=0.037$). Baseline volumes of whole brain ($r=0.476$, $p=0.002$), gray matter ($r=0.467$, $p=0.002$), T1 ($r=-0.627$, $p<0.001$), and T2 lesion volumes ($r=-0.475$, $p=0.002$) correlated significantly with baseline SDMT. Longitudinal analyses showed that both MRI volumes and EDSS were associated with the rate of SDMT decline, whereas sNfL and cNfL were not. Conclusion. NfL levels measured in serum and cerebrospinal fluid were both associated with cognitive functioning in MS patients over a 10-year period from diagnosis. However, MRI volumes correlated strongly in addition to the rate of cognitive decline.