Association of serum levels of inflammation and oxidative stress markers with cognitive outcomes in multiple sclerosis; a systematic review

Background: Multiple sclerosis (MS) is an immune-mediated disease with cognitive impairment being a crucial manifestation. Oxidative stress and inflammation play significant roles in the disease's pathogenesis. This systematic review explores the association between inflammation and oxidative stress markers, with cognitive outcomes in MS patients. Methods: This study adhered to the Joanna Briggs Institute (JBI) and PRISMA 2020 methods. Eligibility criteria included studies with MS patients, evaluating serum inflammation and/or oxidative stress markers, assessing cognitive function, and examining the relationship between these factors. PubMed, Scopus, Embase, and Web of Science, were searched and the risk of bias was assessed using the JBI checklists. Results: Out of 1609 identified records, 10 studies were included in this systematic review. The studies were published between 2006 and 2023 and involved 629 MS patients. Current evidence suggests a negative correlation between TNF-alpha, and cognitive outcomes in MS (reported in three out of five studies). Associations between the decreased native and total thiol levels, as well as interleukin (IL)-17A with cognitive impairment, and the correlation between IL-6 and C-reactive protein (CRP) with cognitive scores in MS are also reported (one study for each). IL-10 (four studies), glutathione peroxidase (GPX), reduced glutathione (GSH), catalase activity (CAT), ischemia-modified albumin (IMA), IL-8, IL-18, and IL-2 (one study for each) did not found to be associated with cognition in MS and evidence regarding the possible role of interferon-gamma (IFN-gamma), total antioxidant capacity (TAC), and malondialdehyde (MDA) is not definitive. Discussion: The review findings suggest a complex association between oxidative stress and inflammation with cognitive outcomes in MS. Diversity in study designs, participant characteristics, and assessment methods makes the findings of this study inconclusive and highlights the need for future research.