Predictors of Cognitive Stability in Multiple Sclerosis: A Longitudinal Analysis
Mahsa Mohajery1, Armistead Williams2, James Stark2, Stavra Romas2
1Tisch MS Research Center of New York, 2IMSMP
Objective:
To identify demographic, clinical, and imaging features associated with cognitive stability in patients with Multiple Sclerosis.
Background:
Cognitive impairment (CI) affects up to half of MS patients and may progress independently of physical disability. Yet, some maintain stable cognition for years. Understanding predictors of preserved cognition may inform individualized management and follow-up strategies.
Design/Methods:
We retrospectively analyzed 36 MS patients who underwent at least two neuropsychological assessments between 2003 and 2024 (intervals 8–22 years). Cognitive performance was categorized as cognitively normal (CN), mild cognitive impairment (MCI; one domain affected), or cognitive impairment (CI; ≥2 domains affected). Baseline variables included sex, age, education, employment, disease duration, Expanded Disability Status Scale (EDSS), MS subtype, disease-modifying therapy (DMT) exposure, and MRI findings (including spinal and cerebellar involvement). Patients with other neurological or psychiatric disorders were excluded. Group comparisons used nonparametric and categorical tests.
Results:
At last evaluation, 18 patients (50%) were CN, 12 (33%) MCI, and 6 (17%) CI. All CI patients had secondary progressive MS (SPMS); 7 CN and 6 MCI patients also had SPMS. CI patients were older with longer disease duration, though differences were not significant. Education years were similar across groups. All CI patients had cerebellar lesions, compared with 2 CN and 3 MCI patients. High-efficacy DMTs (B-cell therapy or natalizumab) were used in all CI and 11 CN patients. CI patients showed impairment in processing speed and visual learning.
Conclusions:
Despite long follow-up, half of patients maintained cognitive stability. CI was more common among SPMS patients and those with cerebellar involvement, whereas age, education, disease duration, and EDSS were not significant predictors. NeuroQuant data are available, and analyses are ongoing to explore structural correlates of cognition. Future studies with larger cohorts are warranted to clarify predictors of cognitive stability and resilience.
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