The cognitive relevance of non-lesional damage to cortical networks in people with multiple sclerosis

Background: Cognitive impairment, a common and debilitating symptom in people with multiple sclerosis (MS), is especially related to cortical damage. However, the impact of regional cortical damage remains poorly understood. Our aim was to evaluate structural (network) integrity in lesional and non-lesional cortex in people with MS, and its relationship with cognitive dysfunction. Methods: In this cross-sectional study, 176 people with MS and 48 healthy controls underwent MRI, including double inversion recovery and diffusion-weighted scans, and neuropsychological assessment. Cortical integrity was assessed based on fractional anisotropy (FA) and mean diffusivity (MD) within 212 regions split into lesional or non-lesional cortex, and grouped into seven cortical networks. Integrity was compared between people with MS and controls, and across cognitive groups: cognitively-impaired (CI; ≥ two domains at Z ≤ − 2 below controls), mildly CI (≥ two at − 2 < Z ≤ − 1.5), or cognitively-preserved (CP). Results: Cortical lesions were observed in 87.5% of people with MS, mainly in ventral attention network, followed by limbic and default mode networks. Compared to controls, in non-lesional cortex, MD was increased in people with MS, but mean FA did not differ. Within the same individual, MD and FA were increased in lesional compared to non-lesional cortex. CI-MS exhibited higher MD than CP-MS in non-lesional cortex of default mode, frontoparietal and sensorimotor networks, of which the default mode network could best explain cognitive performance. Conclusion: Diffusion differences in lesional cortex were more severe than in non-lesional cortex. However, while most people with MS had cortical lesions, diffusion differences in CI-MS were more prominent in non-lesional cortex than lesional cortex, especially within default mode, frontoparietal and sensorimotor networks

Altered functional brain states predict cognitive decline 5 years after a clinically isolated syndrome

© The Author(s), 2022.Background: Cognitive impairment occurs in the earliest stages of multiple sclerosis (MS) together with altered functional connectivity (FC). Objective: The aim of this study was to investigate the evolution of dynamic FC states in early MS and their role in shaping cognitive decline. Methods: Overall, 32 patients were enrolled after their first neurological episode suggestive of MS and underwent cognitive evaluation and resting-state functional MRI (fMRI) over 5 years. In addition, 28 healthy controls were included at baseline. Results: Cognitive performance was stable during the first year and declined after 5 years. At baseline, the number of transitions between states was lower in MS compared to controls (p = 0.01). Over time, frequency of high FC states decreased in patients (p = 0.047) and increased in state with low FC (p = 0.035). Cognitive performance at Year 5 was best predicted by the mean connectivity of high FC state at Year 1. Conclusion: Patients with early MS showed reduced functional network dynamics at baseline. Longitudinal changes showed longer time spent in a state of low FC but less time spent and more connectivity disturbance in more integrative states with high within- and between-network FC. Disturbed FC within this more integrative state was predictive of future cognitive decline

Effect of cognitive rehabilitation on neuropsychological and semiecological testing and on daily cognitive functioning in multiple sclerosis: The REACTIV randomized controlled study

International audienceBackground: Specific cognitive rehabilitation (SCR) has been suggested for multiple sclerosis (MS). A randomized controlled trial (RCT) evaluating the therapeutic effects of SCR is necessary.Objective: To demonstrate the superiority of a SCR program (REACTIV) over nonspecific intervention (NSI) for neuropsychological (NP) assessment, virtual reality (VR) cognitive testing and daily cognitive functioning.Methods: A single-blind RCT compared SCR and NSI in patients with MS with cognitive complaint. Both programs included 50 individual sessions, 3 times a week for 17 weeks in a real-world setting. The primary end-point was NP assessment. Secondary end-points included semiecological VR tasks (Urban Daily Cog®) and daily cognitive functioning assessment. Maintenance of the effects at 8 months was studied.Results: Of the 35 patients, 18 completed the SCR, and 17 completed the NSI. Several NP and semiecological scores improved significantly more after SCR than after NSI. More NP scores improved significantly after SCR than after NSI. SCR improved daily cognitive functioning. Most improvements were maintained at 8 months.Conclusion: SCR performed in a real-world setting is superior to NSI for improving performance in specific cognitive domains and information processing speed, and for improving cognitive functioning, as evaluated by ecological tools close to daily life and a daily cognitive functioning questionnaire