Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

Modica, Claire; Bergsland, Niels; Dwyer, Michael G.; Ramasamy, Deepa P.; Carl, Ellen; Zivadinov, Robert; Benedict, Ralph H. B.

doi:10.1177/1352458515579443

Cited by 60 publications

(45 citation statements)

References 35 publications

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“…In contrast, the level of formal education had significant influence on the SDMT (p < 0.01) and CVLT (p < 0.05). This effect of protection on the NTs is a replication of previous data widely suggested by other authors 8, 19,25,28,29 . Interestingly, a study performed in the last decade 5 suggested cut-off points for the SDMT accordance with educational level of patients and considered differences of 1, 1.5 and 2 SD below the mean of normal controls as cognitive impairment, reinforcing the importance of the impact of this variable on NTs.…”

supporting

confidence: 90%

The correlation between EDSS and cognitive impairment in MS patients. Assessment of a Brazilian population using a BICAMS version

Caneda

Vecino

2016

Arq. Neuro-Psiquiatr.

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Multiple sclerosis (MS) may present with a cognitive impairment as disabling as the physical disabilities. Therefore, routine cognitive evaluation is pivotal. Valid and reliable neuropsychological tests are essential in follow-up and to define future therapeutic interventions. Objectives To investigate the correlation between the disabilities of MS patients and their cognitive impairment assessed by the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS). Methods Forty patients with definitive diagnoses of MS were selected. The correlation coefficient (r) between the Expanded Disability Status Scale (EDSS) and the neuropsychological tests of BICAMS were calculated. Results The correlation was clinically substantial and significant with r = 0.55 (p < 0.01) in the Symbol Digit Modalities Test (SDMT), 0.54 (p < 0.01) in the Brief Visuospacial Memory Test (BVMT) and 0.40 (p < 0.05) in the California Verbal Learning Test (CVLT). Conclusion BICAMS has easy and satisfactory application and evaluation for routine visits and presents a significant correlation with the EDSS. Its use may be indicated for screening and monitoring of cognitive impairment in patients with MS.

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supporting

confidence: 90%

The correlation between EDSS and cognitive impairment in MS patients. Assessment of a Brazilian population using a BICAMS version

Caneda

Vecino

2016

Arq. Neuro-Psiquiatr.

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“…Our findings are in line with the well-established concept that the DGM are an early and common site of atrophy in patients with MS [17][18][19][20][21][22][35][36][37][38], which progresses longitudinally [20,21,36,37,[39][40][41]. The magnitude of decreased DGM volumes we demonstrated in our study during the observation period is inline with these previous studies.…”

Section: Discussionsupporting

confidence: 93%

“…GM and white matter (WM) pathology are not necessarily closely coupled [15]. Furthermore, previous studies have shown that the deep gray matter (DGM, i.e., basal ganglia and thalamus) is disproportionately affected as compared to the cortical GM [17] and whole brain [18,19] and such involvement is highly clinically relevant [19][20][21][22]. Regarding the methodology available to assess brain volume loss from MRI CONTACT Rohit Bakshi rbakshi@post.harvard.edu scans, recent data indicate advantages of 3T vs. 1.5T MRI for accuracy and validity [23], which parallels its advantages in assessing lesions [24][25][26].…”

Section: Original Articlementioning

confidence: 99%

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis

Kim

Chu

Yousuf

et al. 2017

International Journal of Neuroscience

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Objective: The subcortical deep gray matter (DGM) develops selective, progressive, and clinically relevant atrophy in progressive forms of multiple sclerosis (PMS). This patient population is the target of active neurotherapeutic development, requiring the availability of outcome measures. We tested a fully automated MRI analysis pipeline to assess DGM atrophy in PMS. Design/Methods: Consistent 3D T1-weighted high-resolution 3T brain MRI was obtained over one year in 19 consecutive patients with PMS [15 secondary progressive, 4 primary progressive, 53% women, age (mean §SD) 50.8 §8.0 years, Expanded Disability Status Scale (median, range) 5.0, 2.0-6.5)]. DGM segmentation applied the fully automated FSL-FIRST pipeline (http://fsl.fmrib.ox.ac.uk). Total DGM volume was the sum of the caudate, putamen, globus pallidus, and thalamus. On-study change was calculated using a random-effects linear regression model. A treatment trial for an intervention that would show a 50% reduction in DGM brain atrophy would require a sample size of 123 patients for a single-arm study (one-year run-in followed by one-year on-treatment). For a two-arm placebo-controlled one-year study, 242 patients would be required per arm. The use of DGM fraction required more patients. The thalamus, putamen, and globus pallidus, showed smaller effect sizes in their on-study changes than the total DGM; however, for the caudate, the effect sizes were somewhat larger. Conclusions: DGM atrophy may prove efficient as a short-term outcome for proof-of-concept neurotherapeutic trials in PMS.

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“…Interestingly, even though decline in SDMT over 3 years was associated with morphological abnormalities in the thalamus; 102 as a group, MS patients were stable on the test compared to HCs. 103,104 Most notably, the SDMT is not a pure test of processing speed. SDMT performance can be influenced by visual acuity and ocular motor functions, 10,105 and while SDMT is correlated with other processing speed tests, there is undoubtedly some incidental learning of symbol–digit associations, and hence the need for alternate forms.…”

Section: Discussionmentioning

confidence: 99%

Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis

et al. 2017

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Cognitive and motor performance measures are commonly employed in multiple sclerosis (MS) research, particularly when the purpose is to determine the efficacy of treatment. The increasing focus of new therapies on slowing progression or reversing neurological disability makes the utilization of sensitive, reproducible, and valid measures essential. Processing speed is a basic elemental cognitive function that likely influences downstream processes such as memory. The Multiple Sclerosis Outcome Assessments Consortium (MSOAC) includes representatives from advocacy organizations, Food and Drug Administration (FDA), European Medicines Agency (EMA), National Institute of Neurological Disorders and Stroke (NINDS), academic institutions, and industry partners along with persons living with MS. Among the MSOAC goals is acceptance and qualification by regulators of performance outcomes that are highly reliable and valid, practical, cost-effective, and meaningful to persons with MS. A critical step for these neuroperformance metrics is elucidation of clinically relevant benchmarks, well-defined degrees of disability, and gradients of change that are deemed clinically meaningful. This topical review provides an overview of research on one particular cognitive measure, the Symbol Digit Modalities Test (SDMT), recognized as being particularly sensitive to slowed processing of information that is commonly seen in MS. The research in MS clearly supports the reliability and validity of this test and recently has supported a responder definition of SDMT change approximating 4 points or 10% in magnitude.

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Cognitive reserve moderates the impact of subcortical gray matter atrophy on neuropsychological status in multiple sclerosis

Abstract: SCGM atrophy occurs in normal controls, but significantly more so in MS. While CPS did not change in normal controls, low cognitive reserve was associated with CPS decline in MS. High cognitive reserve protect MS patients from cognitive decline related to SCGM atrophy.

Cited by 60 publications

References 35 publications

The correlation between EDSS and cognitive impairment in MS patients. Assessment of a Brazilian population using a BICAMS version

The correlation between EDSS and cognitive impairment in MS patients. Assessment of a Brazilian population using a BICAMS version

Sample size requirements for one-year treatment effects using deep gray matter volume from 3T MRI in progressive forms of multiple sclerosis

Validity of the Symbol Digit Modalities Test as a cognition performance outcome measure for multiple sclerosis

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