Neurocognitive Impairment in Multiple Sclerosis and Its Association With Thiol-Disulfide Homeostasis and Ischemia-Modified Albumin

Abstract

This study aimed to assess the possible association between cognitive impairment and two important biochemical biomarkers of oxidative stress, thiol-disulfide homeostasis (TDH), and ischemia-modified albumin (IMA) in patients with multiple sclerosis (MS). This study included 85 patients with MS (38 treatment-naive relapsing-remitting MS (RRMS), 31 RRMS on fingolimod therapy, and 16 secondary progressive MS (SPMS)) and 33 healthy controls. Cognitive evaluation was carried out by applying the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) test battery and the scores were adjusted for age and years of education. Plasma TDH was assessed using an automated method and plasma IMA levels were determined using the cobalt-albumin binding assay. Plasma native thiol and total thiol levels were significantly decreased in patients with SPMS when compared with the naive patients and healthy controls. Cognitive impairment was detected in 47.4% of naive patients, 64.5% of patients on fingolimod therapy, and 80% of patients with SPMS. Naive patients or patients on fingolimod therapy who were cognitively impaired had significantly decreased levels of native thiol and total thiol compared to the cognitively normal patients. Logistic regression analysis revealed total thiol and native thiol to be significantly associated with cognitive impairment in naive patients and patients on fingolimod therapy. Significant correlations were determined between BICAMS scores, TDH, IMA, clinical indices of disease severity (EDSS and MSSS), and magnetic resonance imaging parameters. This study has shown for the first time that plasma TDH parameters are associated with cognitive impairment in MS.