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Background and Purpose: To predict disability and cognition in multiple sclerosis (MS) after 6 and 12 years, using early clinical and imaging measures., Methods: A total of 115 patients with MS were selected and followed up after 2 and 6 years, with 79 patients also being followed up after 12 years. Disability was measured using the Expanded Disability Status Scale (EDSS); cognition was measured only at follow-up using neuropsychological testing. Predictors of interest included EDSS score, baseline brain and lesion volumes and their changes over 2 years, baseline age, clinical phenotype, sex and educational level., Results: Higher 6-year EDSS score was predicted by early EDSS score and whole-brain volume changes and baseline diagnosis of primary progressive MS (adjusted R 2  = 0.56). Predictors for 12-year EDSS score included larger EDSS score changes and higher T1-hypointense lesion volumes (adjusted R 2  = 0.38). Year 6 cognition was predicted by primary progressive MS phenotype, lower educational level, male sex and early whole-brain atrophy (adjusted R 2  = 0.26); year 12 predictors included male sex, lower educational level and higher baseline T1-hypointense lesion volumes (adjusted R 2  = 0.14)., Conclusions: Patients with early signs of neurodegeneration and a progressive disease onset were more prone to develop both disability progression and cognitive dysfunction. Male sex and lower educational level only affected cognitive dysfunction, which remains difficult to predict and probably needs more advanced imaging measures., (© 2019 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC., Competing Interests: Compliance with ethical standards Disclosures Mr. van Geest serves as a consultant for Novartis. Ms. Westerik reports no disclosures. Dr. van der Werf received a speakers fee from Lundbeck in 2014 and performs contract research sponsored by Photopharmics, Inc., USA. Dr. Geurts serves on the editorial boards of MS Journal, BMC Neurology, MS International and Neurology and the Scientific Advisory Board of the Dutch MS Research Foundation and of MS Academia, Merck-Serono and has served as a consultant for Merck-Serono, Biogen Idec, Novartis, Genzyme and Teva Pharmaceuticals. Dr. Hulst receives research support from the Dutch MS Research Foundation, Grant Number 08-648 and serves as a consultant for Genzyme, Merck-Serono, Teva Pharmaceuticals and Novartis. Conflicts of interest The authors declare that they have no conflict of interest.

Background: Cognitive dysfunction in multiple sclerosis (MS) has a large impact on the quality of life and is poorly understood., Objective: The aim of this study was to investigate functional network integrity in MS, and relate this to cognitive dysfunction and physical disability., Methods: Resting state fMRI scans were included of 128 MS patients and 50 controls. Eigenvector centrality mapping (ECM) was applied, a graph analysis technique that ranks the importance of brain regions based on their connectivity patterns. Significant ECM changes were related to physical disability and cognitive dysfunction., Results: In MS patients, ECM values were increased in bilateral thalamus and posterior cingulate (PCC) areas, and decreased in sensorimotor and ventral stream areas. Sensorimotor ECM decreases were related to higher EDSS (rho = -0.24, p = 0.007), while ventral stream decreases were related to poorer average cognition (rho = 0.23, p = 0.009). The thalamus displayed increased connectivity to sensorimotor and ventral stream areas., Conclusion: In MS, areas in the ventral stream and sensorimotor cortex appear to become less central in the entire functional network of the brain, which is associated with clinico-cognitive dysfunction. The thalamus, however, displays increased connectivity with these areas. These findings may aid in further elucidating the function of functional reorganization processes in MS., (© The Author(s) 2013.)

Brain networks and cognition have recently begun to attract attention: studies suggest that more efficiently wired resting-state brain networks are indeed correlated with better cognitive performance. "Small-world" brain networks combine local segregation with global integration, hereby subserving information processing. Furthermore, recent studies implicate that gender effects may be present in both network dynamics and its correlations with cognition. This study reports on the relation between resting-state functional brain topology with overall and domain-specific cognitive performance in healthy participants and possible gender differences herein. Healthy participants underwent neuropsychological tests, of which individual scores were converted to z-scores. Network analysis was performed on resting-state, eyes-closed magnetoencephalography (MEG) data, after determining functional connectivity between each pair of sensors. The clustering coefficient (local specialization), average path length (overall integration and efficiency) and "small-world index" (i.e. ratio between clustering and path length) were calculated in six frequency bands. 14 male and 14 female participants were included. Better total cognitive performance was related to increased local connectivity in the theta band, higher clustering coefficient (in delta and theta bands) and higher small-worldness (in theta and lower gamma bands). Women showed less clustering and shorter path length in the delta band. There were no significant correlations between network topology and cognitive functioning in females. In contrast, higher cognitive scores in men were associated with increased theta band clustering and small-worldness. These results provide further evidence for the value of functional brain network topology for cognitive functioning and suggest that gender is an important factor in this respect., (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)

Background and purpose: To predict disability and cognition in multiple sclerosis (MS) after 6 and 12 years, using early clinical and imaging measures. Methods: A total of 115 patients with MS were selected and followed up after 2 and 6 years, with 79 patients also being followed up after 12 years. Disability was measured using the Expanded Disability Status Scale (EDSS); cognition was measured only at follow‐up using neuropsychological testing. Predictors of interest included EDSS score, baseline brain and lesion volumes and their changes over 2 years, baseline age, clinical phenotype, sex and educational level. Results: Higher 6‐year EDSS score was predicted by early EDSS score and whole‐brain volume changes and baseline diagnosis of primary progressive MS (adjusted R2 = 0.56). Predictors for 12‐year EDSS score included larger EDSS score changes and higher T1‐hypointense lesion volumes (adjusted R2 = 0.38). Year 6 cognition was predicted by primary progressive MS phenotype, lower educational level, male sex and early whole‐brain atrophy (adjusted R2 = 0.26); year 12 predictors included male sex, lower educational level and higher baseline T1‐hypointense lesion volumes (adjusted R2 = 0.14). Conclusions: Patients with early signs of neurodegeneration and a progressive disease onset were more prone to develop both disability progression and cognitive dysfunction. Male sex and lower educational level only affected cognitive dysfunction, which remains difficult to predict and probably needs more advanced imaging measures. [ABSTRACT FROM AUTHOR]

Sleep disturbances are common in multiple sclerosis (MS), but its impact on cognition and functional connectivity (FC) of the hippocampus and thalamus is unknown. Therefore, we investigated the relationship between sleep disturbances, cognitive functioning and resting-state (RS) FC of the hippocampus and thalamus in MS. 71 MS patients and 40 healthy controls underwent neuropsychological testing and filled out self-report questionnaires (anxiety, depression, fatigue, and subjective cognitive problems). Sleep disturbances were assed with the five-item version of the Athens Insomnia Scale. Hippocampal and thalamic volume and RS FC of these regions were determined. Twenty-three patients were categorized as sleep disturbed and 48 as normal sleeping. No differences were found between disturbed and normal sleeping patients concerning cognition and structural MRI. Sleep disturbed patients reported more subjective cognitive problems, and displayed decreased FC between the thalamus and middle and superior frontal gyrus, inferior frontal operculum, anterior cingulate cortex, inferior parietal gyrus, precuneus, and angular gyrus compared to normal sleeping patients. We conclude that sleep disturbances in MS are not (directly) related to objective cognitive functioning, but rather to subjective cognitive problems. In addition, sleep disturbances in MS seem to coincide with a specific pattern of decreased thalamic FC. [ABSTRACT FROM AUTHOR]

The article examines functional network integrity in multiple sclerosis (MS) and relate this to cognitive dysfunction and physical disability in MS patients. It is said that the quality of life is hugely influenced by cognitive dysfunction in MS. The study included 128 MS patients and 50 controls on whom resting state fMRI scans were done.