Circulatory antioxidant and oxidative stress markers are in correlation with demographics but not cognitive functions...

Multiple sclerosis (MS) is the most common non-traumatic cause of disability in younger adults. MS can be presented with a wide range of symptoms such as cognitive impairment (CI). Oxidative stress (OXS) is a major basis of the pathogenesis of MS. There is a positive correlation between OXS factors and the progression of the disease in MS patients. There are limited studies regarding the role of OXS in MS-related CI. In this study, as an exploratory analysis, we assess the role of endogenous antioxidants and OXS factors in cognitive function, the severity of disability due to MS, and demographic findings in a sample of MS patients.

Adult (>18 years old) patients with a definite diagnosis of MS based on 2017 revised MacDonald criteria were included in this study. The neurophysiological assessment was conducted, using the validated Persian version of minimal assessment of cognitive function in multiple sclerosis (MACFIMS) battery, which is composed of seven different tests. Based on the structure of the battery, CI was defined as a failure in at least two different components of the MACFIMS battery. The patients were separated into two groups of CI and non-CI. Examined antioxidant factors included catalase Activity (CAT), Glutathione Peroxidase 1 (GPX1), Glutathione Peroxidase 2 (GPX2), Reduced Glutathione (GSH), Superoxide Dismutase (SOD), and serum total antioxidant capacity (TAC). Malondialdehyde (MDA) was also measured as an OXS marker.

71 patients were involved in this study. The type of MS was relapsing-remitting MS (RRMS) in 80.28% of the participants. Disease duration (P<0.01), type of MS (p<0.01), and EDSS score (p<0.01) were different between CI and non-CI groups, but there were not any significant differences in CAT (p = 0.80), GPX1 (p = 0.71), GPX2 (p = 0.41), GSH (p = 0.96), TAC (p = 0.13), SOD (p = 0.37), and MDA (p = 0.82). A significant difference between RRMS and progressive MS (PMS) patients in the levels of GPX1 (p = 0.01), GPX2 (p = 0.01), and SOD (p = 0.01) was observed. Also, we found higher circulatory levels of CAT (p = 0.02) and TAC (p<0.01) in male MS patients. We found significant correlations between aging and CAT (R = 0.28; p = 0.01), GPX1 (R = 0.36; p<0.01), GPX2 (R = 0.34; p<0.01), and SOD (R = 0.40; p<0.01). EDSS, the duration of the disease, relapse rate, and the number of impaired cognitive tasks were not correlated with any of investigated OXS or antioxidant factors (p>0.05). In terms of a detailed investigation of associations between MACFIMS battery components and levels of OXS and antioxidant factors, there were no significant relations in this regard (p>0.05). Based on the logistic regression multivariate analysis, only disease duration (p = 0.03) and GPX1 (p = 0.01) were independently associated with CI in MS patients in our sample.

The circulatory levels of GPX1, GPX2, and SOD are significantly different between RRMS and PMS patients. Neither endogenous antioxidants nor MDA, as an OXS biomarker, are associated with the cognitive function or level of physical disability in MS patients. Limitations of this study suggest a need for future studies in a larger sample of MS patients.