Isolated cognitive impairment in people with multiple sclerosis: frequency, MRI patterns and its development over time

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Objectives: To study the frequency of isolated (i.e., single-domain) cognitive impairments, domain specific MRI correlates, and its longitudinal development in people with multiple sclerosis (PwMS). Methods: 348 PwMS (mean age 48 ± 11 years, 67% female, 244RR/52SP/38PP) underwent neuropsychological testing (extended BRB-N) at baseline and at five-year follow-up. At baseline, structural MRI was acquired. Isolated cognitive impairment was defined as a Z-score of at least 1.5 SD below normative data in one domain only (processing speed, memory, executive functioning/working memory, and attention). Multi-domain cognitive impairment was defined as being affected in ≥ 2 domains, and cognitively preserved otherwise. For PwMS with isolated cognitive impairment, MRI correlates were explored using linear regression. Development of isolated cognitive impairment over time was evaluated based on reliable change index. Results: At baseline, 108 (31%) PwMS displayed isolated cognitive impairment, 148 (43%) PwMS displayed multi-domain cognitive impairment. Most PwMS with isolated cognitive impairment were impaired on executive functioning/working memory (EF/WM; N = 37), followed by processing speed (IPS; N = 25), memory (N = 23), and attention (N = 23). Isolated IPS impairment was explained by a model of cortical volume and fractional anisotropy (adj. R 2 = 0.539, p < 0.001); memory by a model with cortical volume and hippocampal volume (adj. R 2 = 0.493, p = 0.002); EF/WM and attention were not associated with any MRI measure. At follow-up, cognitive decline was present in 11/16 (69%) of PwMS with isolated IPS impairment at baseline. This percentage varied between 18 and 31% of PwMS with isolated cognitive impairment in domains other than IPS at baseline. Conclusion: Isolated cognitive impairment is frequently present in PwMS and can serve as a proxy for further decline, particularly when it concerns processing speed. Cortical and deep grey matter atrophy seem to play a pivotal role in isolated cognitive impairment. Timely detection and patient-tailored intervention, predominantly for IPS, may help to postpone further cognitive decline.

Original languageEnglish
Pages (from-to)2159-2168
Number of pages10
JournalJournal of neurology
Issue number5
Early online date2024
Publication statusPublished - May 2024


  • Cognition
  • Cognitive rehabilitation
  • Isolated cognitive impairment
  • MRI
  • Multiple sclerosis

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