Cognition and Disability in AQP4-IgG NMOSD

Background/Objectives: Cognitive impairment in neuromyelitis optica spectrum disorder (NMOSD) is increasingly recognized, but its profile and clinical correlates remain uncertain. This study sought to describe cognitive performance in individuals with NMOSD and to explore its associations with disease activity, disability level, and immunosuppressive treatment. Methods: This exploratory cross-sectional study characterized cognitive performance in 36 AQP4-IgG-positive individuals with NMOSD and 18 healthy volunteers using domain-level cognitive scores adjusted for age, education, and visual acuity. Results: Cognitive impairment was present in at least one domain in 27 participants, most frequently affecting memory (36%), praxis (33%), and information processing speed (IPS; 31%). IPS was the only domain significantly impaired in NMOSD compared with controls in unadjusted analyses (p = 0.007), but no domain remained significantly different after adjustment, despite a medium-to-large effect for IPS. Higher disability burden was associated with worse IPS (p = 0.011) and with lower scores on a clinically sensitive cognitive composite integrating memory, IPS, and executive function (β = –0.125, p = 0.040). Among clinical activity measures, annualized relapse rate showed a positive association only with executive function (β = 0.282, p = 0.007), whereas neither relapse count nor immunosuppressive treatment was associated with cognitive performance. Conclusions: These findings indicate a heterogeneous cognitive profile in NMOSD strongly influenced by demographic and sensory factors, with disability burden appearing to be more closely associated with cognitive performance than relapse-based activity.