Does cognitive dysfunction correlate with neurofilament light polypeptide levels in the CSF of patients with multiple sclerosis?

Abstract

Objective To investigate whether neurofilament light polypeptide (NfL) level in cerebrospinal fluid (CSF), currently a prognostic biomarker of neurodegeneration in patients with multiple sclerosis (MS), may be a potential biomarker of cognitive dysfunction in MS. Methods This observational case–control study included patients with MS. CSF levels of NfL were determined using enzyme-linked immunosorbent assay. Cognitive function was measured with the Brief International Cognitive Assessment for MS (BICAMS) battery and Paced Auditory Serial Addition Test (PASAT3), standardized to the Greek population. Results Of 39 patients enrolled (aged 42.7 ± 13.6 years), 36% were classified as cognitively impaired according to BICAMS z-scores (–0.34 ± 1.13). Relapsing MS was significantly better than progressive forms regarding BICAMS z-score (mean difference [MD] 1.39; 95% confidence interval [CI] 0.54, 2.24), Symbol Digit Modality Test score (MD 1.73; 95% CI 0.46, 3.0) and Greek Verbal Learning Test (MD 1.77; 95% CI 0.82, 2.72). An inversely proportional association between CSF NfL levels and BICAMS z-scores was found in progressive forms of MS (rp = –0.944). Conclusions This study provides preliminary evidence for an association between CSF NfL levels and cognition in progressive forms of MS, which requires validation in larger samples.

Serum neurofilament light chain

“…They argued that this might be traced to greater gray matter degeneration, expressed in higher NfL levels, in the progressive subtype. 19 Visuospatial learning and memory were indeed defined within 1 cognitive cluster along with information processing speed, both being frequently and severely affected in the course of the disease and thus constituting sensitive domains for cognitive screening, particularly in SPMS. 33,34 Other studies correspondingly observed information processing speed to be linked with NfL derived from plasma, 35 CSF, 17,18 and serum.…”

“…8,9 In MS, CSF NfL levels correlate with classical relapses and disability. [10][11][12] Recently, the single molecule array (Simoa) immunoassay technology 13 with unprecedented analytical sensitivity enabled the detection of subtle NfL levels even in serum samples 14 and successfully linked serum NfL (sNfL) to neuroaxonal damage and therapy effects in MS. 15,16 Few studies though specifically explored NfL as a biomarker of cognitive performance and fatigue in MS. [17][18][19][20][21][22] Importantly, most of them measured NfL levels in CSF, although studies on sNfL levels and cognition, fatigue, depression, or anxiety are rare.…”

The relationship between neurofilament light chain and cognition in neurological disorders: A scoping review

“…These studies showed that higher levels of NfL were associated with decreased cognition; specifically, poorer performance on measures of working memory, executive function information processing speed, verbal fluency, attentional control, and verbal, episodic and semantic memory. This was evidenced by decreased performance on the Paced Auditory Serial Addition Test (PASAT), a composite score from the Brief International Cognitive Assessment for MS (BICAMS), Word List Generation (WLG), Variable Attentional Control (VAC), Delis-Kaplan Executive Function System (DKEFS), and the Brief Repeatable Battery (BRB) in individuals with higher levels of NfL [30,40,52,57,68,91]. The subsets of the BRB showing the highest correlation with NfL were those assessing information processing speed [30] as well as memory [52].…”

Neurofilaments: The C-Reactive Protein of Neurology

“…This is most likely due to the emphasis on gait performance in the EDSS that may overestimate the influence of spinal cord lesions over cerebral lesions, which can be extensive even at low EDSS scores. Whether NF-L levels also correlate with cognitive measures and fatigue in MS remains to be confirmed although recent studies seem to suggest a negative correlation [23,[111][112][113].…”