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Novel computer-based testing shows multi-domain cognitive dysfunction in patients with multiple sclerosis.

ABSTRACT: Background:Although cognitive dysfunction is a leading cause of disability and poor quality of life in patients with multiple sclerosis (MS), it is infrequently tested in routine clinical evaluation. Development of a cognitive testing paradigm that captured MS-related cognitive dysfunction and could be obtained in a routine clinical setting may increase surveillance and recognition of cognitive dysfunction. Objectives:This was a pilot study to determine if Cognivue could find cognitive performance differences between patients with MS and healthy controls (HC).Methods: A total of 24 patients with MS and 12 HCs between 18 and 50 years old were enrolled. Baseline testing included an Expanded Disability Scale (EDSS), paced auditory serial additions test (PASAT), symbol digit modalities test (SDMT) and Cognivue. Subjects then had repeat testing every 1-2 months for a maximum of three tests. Results:Significant differences were found between MS and HC on SDMT, PASAT, and Cognivue Total score. Most Cognivue subtests showed significant differences between MS and HC. Cognivue scores correlated with both SDMT and PASAT and had high test-retest reliability in HCs. Conclusion:Cognivue was able to detect multi-domain cognitive dysfunction in MS. Further studies to determine validity of Cognivue in MS with comparison with neuropsychological testing and sensitivity to clinical change are still needed.

SUBMITTER: Smith AD

PROVIDER: S-EPMC5993067 | biostudies-literature | 2018 Apr-Jun

REPOSITORIES: biostudies-literature

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Novel computer-based testing shows multi-domain cognitive dysfunction in patients with multiple sclerosis.

Smith Andrew D AD Duffy Charles C Goodman Andrew D AD

Multiple sclerosis journal - experimental, translational and clinical 20180427 2

<h4>Background</h4>Although cognitive dysfunction is a leading cause of disability and poor quality of life in patients with multiple sclerosis (MS), it is infrequently tested in routine clinical evaluation. Development of a cognitive testing paradigm that captured MS-related cognitive dysfunction and could be obtained in a routine clinical setting may increase surveillance and recognition of cognitive dysfunction.<h4>Objectives</h4>This was a pilot study to determine if <i>Cognivue</i> could fi ...[more]

PMID: 29900003

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Project description:Chronic pain in multiple sclerosis is common and difficult to treat. Its mechanisms remain incompletely understood. Dysfunction of the descending pain modulatory system is known to contribute to human chronic pain conditions. However, it is not clear how alterations in executive function influence this network, despite healthy volunteer studies linking function of the descending pain modulatory system, to cognition. In adults with multiple sclerosis-associated chronic neuropathic limb pain, compared to those without pain, we hypothesized altered functional connectivity of the descending pain modulatory system, coupled to executive dysfunction. Specifically we hypothesized reduced mental flexibility, because of potential importance in stimulus reappraisal. To investigate these hypotheses, we conducted a case-control cross-sectional study of 47 adults with relapsing remitting multiple sclerosis (31 with chronic neuropathic limb pain, 16 without pain), employing clinical, neuropsychological, structural, and functional MRI measures. We measured brain lesions and atrophy affecting descending pain modulatory system structures. Both cognitive and affective dysfunctions were confirmed in the chronic neuropathic limb pain group, including reduced mental flexibility (Delis Kaplan Executive Function System card sorting tests P < 0.001). Functional connectivity of rostral anterior cingulate and ventrolateral periaqueductal gray, key structures of the descending pain modulatory system, was significantly lower in the group experiencing chronic neuropathic pain. There was no significant between-group difference in whole-brain grey matter or lesion volumes, nor lesion volume affecting white matter tracts between rostral anterior cingulate and periaqueductal gray. Brainstem-specific lesion volume was higher in the chronic neuropathic limb pain group (P = 0.0017). Differential functional connectivity remained after correction for brainstem-specific lesion volume. Gabapentinoid medications were more frequently used in the chronic pain group. We describe executive dysfunction in people with multiple sclerosis affected by chronic neuropathic pain, along with functional and structural MRI evidence compatible with dysfunction of the descending pain modulatory system. These findings extend understanding of close inter-relationships between cognition, function of the descending pain modulatory system, and chronic pain, both in multiple sclerosis and more generally in human chronic pain conditions. These findings could support application of pharmacological and cognitive interventions in chronic neuropathic pain associated with multiple sclerosis.

Project description:ObjectiveTo evaluate the utility of mismatch negativity (MMN), a neurophysiologic marker of non-motor cognitive processing, in amyotrophic lateral sclerosis (ALS).Methods89 patients, stratified into 4 different phenotypic presentations of ALS (67 spinal-onset, 15 bulbar-onset, 7 ALS-FTD, 7 C9ORF72 gene careers), and 19 matched controls underwent 128-channel EEG data recording. Subjects were presented with standard auditory tones interleaved with pitch-deviant tones in three recording blocks. The MMN response was quantified by peak amplitude, peak delay, average amplitude, and average delay, 100-300 ms after stimuli. 64 patients underwent cognitive screening using the Edinburgh Cognitive and Behavioural ALS Screen (ECAS), and 38 participants underwent contemporaneous cognitive assessment using the Stroop Color-Word Interference test (CWIT), which measures attention shift, inhibitory control, and error monitoring.ResultsThe MMN response was observed in frontal and frontocentral regions of patient and control groups. Compared to controls, waveforms were attenuated in early onset, and the average delay was significantly increased in all of the ALS subgroups, with no significant difference between subgroups. Comparing with the control response, the ALS MMN response clustered into four new subgroups characterized by differences in response latency. The increased average delay correlated with changes in the Stroop CWIT; however, it did not show a direct relationship with age, gender, traditional phenotypes, revised ALS Functional Rating Scale, or ECAS scores.Conclusion and significanceThe MMN response in ALS patients reflects the cognitive dysfunction in specific sub-domains, as the new patient subgroups, identified by cluster analysis, do not segregate with existing clinical or cognitive classifications. Event-related potentials can provide additional quantitative neurophysiologic measures of impairment in specific cognitive sub-domains from which it may be possible to generate novel biologically relevant subgroups of ALS.

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Novel computer-based testing shows multi-domain cognitive dysfunction in patients with multiple sclerosis.

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Novel computer-based testing shows multi-domain cognitive dysfunction in patients with multiple sclerosis.

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