Cognitive Performance and Psychological Characteristics in Patients With Clinically Isolated Syndrome: A Case–Control Study

ABSTRACT Background and Aim Clinically isolated syndrome (CIS) may represent the earliest clinical manifestation of multiple sclerosis (MS). Cognitive and psychological impairments may appear during the early phase of CIS, even in the absence of significant neurological disability. This study evaluated cognitive performance and psychological characteristics in patients with CIS and healthy individuals. Methods This case‐control study enrolled 80 patients with CIS and 80 healthy controls matched for age and sex (mean age 34 years; 48 women per group) at Golestan Hospital (Ahvaz, Iran). Cognitive performance was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB) and Montreal Cognitive Assessment (MoCA). Psychological characteristics were evaluated using the Beck Depression Inventory‐II (BDI‐II), Obsessive Beliefs Questionnaire–44 (OBQ‐44), and Beck Anxiety Inventory (BAI). Nonverbal intelligence was assessed using Raven's Progressive Matrices (RPM). Demographic and clinical data, including Expanded Disability Status Scale (EDSS) scores, were also collected. Results Patients with CIS had mild neurological disability (mean EDSS: 1.18 ± 0.7). Mean scores for depression, anxiety, and obsessive beliefs were significantly higher in patients with CIS than in controls (p < 0.05). Nonverbal intelligence differed significantly between groups, with very high RPM scores observed only among controls (p < 0.05). Patients with CIS also had a significantly lower total MoCA score than controls, as well as a higher rate of mild cognitive impairment and poorer performance on delayed recall, naming, and attention (p < 0.05). CANTAB revealed significantly reduced cognitive performance in patients with CIS compared with controls across motor, attention, memory, and executive function domains (p < 0.05). Conclusion Patients with CIS exhibited mild but statistically significant cognitive and psychological impairments despite minimal neurological disability. These findings highlight the importance of early cognitive and psychological evaluation in patients with CIS to support timely clinical monitoring and management.