Molecular biomarkers and cognitive impairment in multiple sclerosis: State of the field, limitations, and future direction – A systematic review and meta-analysis

• Published in: Neuroscience and biobehavioral reviews 2023-03, Vol.146, p.105035-105035, Article 105035
• Main Authors: Rademacher, Tom-D., Meuth, Sven G., Wiendl, Heinz, Johnen, Andreas, Landmeyer, Nils C.
• Format: Article
• Language: English
• Subjects: Biomarkers; Cognition; Cognitive Dysfunction - psychology; Cognitive impairment; Humans; Meta-analysis; Molecular biomarkers; Multiple sclerosis; Multiple Sclerosis - psychology; Neurofilament light chain; Systematic review; Vitamin D
• ISSN: 0149-7634; 1873-7528
• DOI: 10.1016/j.neubiorev.2023.105035

Multiple sclerosis (MS) is associated with cognitive impairment (CI) such as slowed information processing speed (IPS). Currently, no immunocellular or molecular markers have been established in cerebrospinal fluid and serum analysis as surrogate biomarkers with diagnostic or predictive value for the development of CI. This systematic review and meta-analysis aims to sum up the evidence regarding currently discussed markers for CI in MS. A literature search was conducted on molecular biomarkers of CI in MS, such as neurofilament light chain, chitinases, and vitamin D. 5543 publications were screened, of which 77 entered the systematic review. 13 studies were included in the meta-analysis. Neurofilament light chain (CSF: rp = −0.294, p = 0.003; serum: rp = −0.137, p = 0.001) and serum levels of vitamin D (rp = 0.190, p = 0.014) were associated with IPS outcomes. Neurofilament light chain and vitamin D are promising biomarkers to track impairments in IPS in MS. Further longitudinal research is needed to establish the use of molecular biomarkers to monitor cognitive decline. •A systematic literature search on molecular biomarkers of cognitive impairment in MS was conducted.•77 articles entered the systematic review, and 13 studies were included in the meta-analysis.•Neurofilament light chain and serum vitamin D were associated with impairments in information processing speed.•Neurofilament light chain and vitamin D are promising candidates as molecular biomarkers for cognitive impairment in MS.•Clear advice is given on how to overcome the current issues in this research field.