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Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

ABSTRACT: BACKGROUND:Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T1- and T2-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, clinically accessible imaging techniques that probe molecular changes in GM. OBJECTIVE:To study cortical GM pathology related to CI in MS using glutamate-sensitive chemical exchange saturation transfer (GluCEST) MRI at 7.0?Tesla (7T). METHODS:A total of 20 patients with relapsing-remitting MS and 20 healthy controls underwent cognitive testing, anatomical imaging, and GluCEST imaging. Glutamate-sensitive image contrast was quantified for cortical GM, compared between cohorts, and correlated with clinical measures of CI. RESULTS AND CONCLUSION:Glutamate-sensitive contrast was significantly increased in the prefrontal cortex of MS patients with accumulated disability (p?

SUBMITTER: O'Grady KP

PROVIDER: S-EPMC6424643 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

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Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

O'Grady Kristin P KP Dula Adrienne N AN Lyttle Bailey D BD Thompson Lindsey M LM Conrad Benjamin N BN Box Bailey A BA McKeithan Lydia J LJ Pawate Siddharama S Bagnato Francesca F Landman Bennett A BA Newhouse Paul P Smith Seth A SA

Multiple sclerosis (Houndmills, Basingstoke, England) 20180919 12

<h4>Background</h4>Cognitive impairment (CI) profoundly impacts quality of life for patients with multiple sclerosis (MS). Dysfunctional regulation of glutamate in gray matter (GM) has been implicated in the pathogenesis of MS by post-mortem pathological studies and in CI by in vivo magnetic resonance spectroscopy, yet GM pathology is subtle and difficult to detect using conventional T<sub>1</sub>- and T<sub>2</sub>-weighted magnetic resonance imaging (MRI). There is a need for high-resolution, ...[more]

PMID: 30230400

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Project description:Purpose: Exercise training reveals high potential to beneficially impact cognitive performance in persons with multiple sclerosis (pwMS). Research indicates that high-intensity interval training (HIIT) has potentially higher effects on physical fitness and cognition compared to moderate continuous exercise. This study (i) compares the effects of a 3-week HIIT and moderate continuous exercise training on cognitive performance and cardiorespiratory fitness of pwMS in an overall analysis and (ii) investigates potential effects based on baseline cognitive status in a subgroup analysis. Methods: Seventy-five pwMS were randomly assigned to an intervention (HIIT: 5 × 1.5-min intervals at 95-100% HRmax, 3 ×/week) or active control group (CG: 24 min continuous exercise at 65% HRmax, 3 ×/week). Cognitive performance was assessed pre- and post-intervention with the Brief International Cognitive Assessment for MS (BICAMS). (I) To examine potential within (time) and interaction (time × group) effects in the overall analysis, separate analyses of covariance (ANCOVA) were conducted. (II) For the subgroup analysis, participants were divided into two groups [intact cognition or impaired cognition (>1.5 standard deviation (SD) compared to healthy, age-matched norm data in at least one of the three tests of the BICAMS]. Potential impacts of cognitive status and intervention were investigated with multivariate analyses of variance (MANOVA). Results: Overall analysis revealed significant time effects for processing speed, verbal learning, rel. VO2peak, and rel. power output. A time*group interaction effect was observed for rel. power output. Subgroup analysis indicated a significant main effect for cognition (impaired cognition vs. intact cognition). Subsequent post-hoc analysis showed significant larger effects on verbal learning in pwMS with impaired cognition. Conclusion: Current results need to be confirmed in a powered randomized controlled trial with cognitive performance as primary endpoint and eligibility based on cognitive performance that is assessed prior to study inclusion.

Project description:Background:Cognitive impairment is frequent and disabling in multiple sclerosis (MS). Changes in information processing speed constitute the most important cognitive deficit in MS. However, given the clinical and topographical variability of the disease, cognitive impairment may vary greatly and appear in other forms in addition to slower information processing speed. Our aim was to determine the frequency of cognitive impairment, the principal cognitive domains, and components involved in MS and to identify factors associated with presence of cognitive impairment in these patients in a large series of patients. Methods:Cross-sectional study of 311 patients with MS [236 with relapsing-remitting MS (RRMS), 52 with secondary progressive MS (SPMS), and 23 with primary progressive MS (PPMS)]. Patients' cognitive function was assessed with a comprehensive neuropsychological assessment protocol. Patients displaying deficits in 2 or more cognitive domains were considered to have cognitive impairment associated with MS. We conducted a principal component analysis to detect different cognitive patterns by identifying clusters of tests highly correlated to one another. Results:Cognitive impairment was detected in 41.5% of the sample, and it was more frequent in patients with SPMS and PPMS (P?=?0.002). Expanded Disability Status Scale scores and education were independent predictors of cognitive impairment. Principal component analysis identified seven clusters: attention and basic executive function (including information processing speed), planning and high-level executive function, verbal memory and language, executive and visuospatial performance time, fatigue-depression, visuospatial function, and basic attention and verbal/visual working memory. Mean scoring of components 2 (high-order executive functioning) and 3 (verbal memory-language) was higher in patients with RRMS than in those with PPMS (component 2) and SPMS (component 3). Conclusion:MS is linked to multiple cognitive profiles and disturbances in different domains. This suggests that cognitive alterations in MS are heterogeneous and affect other domains in addition to information processing speed.

Dataset Information

Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

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Glutamate-sensitive imaging and evaluation of cognitive impairment in multiple sclerosis.

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