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Updated: Jul 6, 2025
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Prevalence, Demographic, and Clinical Factors Associated With Cognitive Dysfunction in Patients With Neuromyelitis
Luka Vlahovic1, Jamie McDonald1, Jessica Hinman1
1From the Providence Multiple Sclerosis Center (L.V.), Providence Brain and Spine Institute, Portland, OR; Departments of Neurology and Neurological Sciences (J.M., A.T., C.L., G.D., M.H.H.), and Epidemiology and Population Health (J.H., L.M.N.), Stanford University School of Medicine; Sparta Science (J.H.), Menlo Park, CA; Department of Pediatrics (C.P., L.J.C.), Data Coordinating Center, University of Utah School of Medicine, Salt Lake City; Department of Medicine (M.R.Y.), Geffen School of Medicine, University of California, Los Angeles; Division of Molecular Medicine (M.R.Y.), and The Lundquist Institute for Infection & Immunity, Harbor-UCLA Medical Center (M.R.Y.), Torrance, CA; and Department of Neurology (M.B.), Creighton University School of Medicine, Omaha, NE.
Background And Objectives:
Neuromyelitis optica spectrum disorder (NMOSD) is a chronic CNS demyelinating autoimmune disorder targeting the astrocyte antigen aquaporin-4 (AQP4), typically presenting with optic neuritis, transverse myelitis, and brain syndromes. Cognitive dysfunction (CD) in NMOSD is under-recognized and poorly understood. The purpose of this study was to evaluate the prevalence and clinical variables associated with CD in NMOSD.
Methods:
This observational retrospective study with longitudinal follow-up describes a clinical cohort seen in the Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD. Serial Montreal Cognitive Assessments (MoCAs) were performed upon enrollment and at 6-month intervals to evaluate longitudinal cognitive function relative to demographic and disease-related factors. We used 2-tailed t test, analysis of variance, the χ2 test, linear regression for univariable and adjusted analyses and simultaneous linear regression and mixed-effects model for multivariable analyses.
Results:
Thirty-four percent (75/219) of patients met criteria for CD (MoCA <26); 29% (64/219) showed mild dysfunction (MoCA 20-26/30), and 5% (11/219) showed moderate (MoCA <20/30) dysfunction. Patients with less neurologic disability and lower pain scores had higher MoCA scores (95% CI 0.24-0.65 and 95% CI 0.09-0.42, respectively). Patients with at least high school education scored higher on the MoCA (95% CI 2.2-5). When comparing patients dichotomized for CD, patients never on rituximab scored higher than patients only treated with rituximab (p < 0.029). There was no significant association between annualized relapse rate, age, sex, disease duration, AQP4 serostatus or brain lesions, and CD. CD was more pronounced among Black than White patients (95% CI -2.7 to -0.7). Multivariable analysis of serial MoCA did not indicate change (p = 0.715). Descriptive analysis of serial MoCA showed 30% (45/150) of patients with worsening MoCA performance had impaired language and verbal recall.
Discussion:
To our knowledge, this is the largest study of diverse cohort to investigate CD in patients with NMOSD. Our findings demonstrate 34% of patients with NMOSD experience mild-to-moderate CD, while 30% of patients demonstrated decline on serial testing. The substantial prevalence of CD in this pilot report highlights the need for improved and validated screening tools and comprehensive measures to investigate CD in NMOSD.
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