Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes

Kletenik, Isaiah; Alvarez, Enríque; Honce, Justin M.; Valdez, Brooke; Vollmer, Timothy; Medina, Luis D.

doi:10.1177/2055217319827618

Cited by 18 publications

(19 citation statements)

References 35 publications

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“…These strategies include controlling cardiovascular risk factors, promoting an active and healthy lifestyle, treating mood disorders, engaging in cognitive and social activities, stress reduction and sleep hygiene. 34 Based on the associations of subjective cognitive concerns with reduced thalamic and cortical grey matter volumes in PwMS, 19 subjective CI could likewise predict further cognitive decline in PwMS. In this context, we recommend that these complaints be monitored in addition to the current neuropsychological screening batteries used in daily practice.…”

Section: Discussionmentioning

confidence: 99%

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Correlates of patient-reported cognitive performance with regard to disability

Laethem

Cock

Schependom

et al. 2021

Preprint

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Background: The inconsistent association of patient−reported Multiple Sclerosis Neuropsychological Questionnaire (MSNQ) scores with performance−based cognitive tests in MS could be related to the degree of disability, due to certain MSNQ−questions assuming some self−dependence and intact instrumental ADLs. Objectives: To test whether the relation between subjective and objective cognitive performance could be moderated by physical disability as measured by the Expanded Disability Status Scale (EDSS), we assessed the correlation between MSNQ and Symbol Digit Modalities Test (SDMT) scores in different EDSS groups. Methods: From 288 MS patients who completed the patient−report MSNQ and a two−question screening tool for depression, we also collected SDMT and EDSS scores. We analysed correlations in the total group and three EDSS subgroups: Low 0.0 − 3.0, Medium 3.5 − 6.0 and High 6.5 − 9.5. Results: We found a significant and negative correlation between patient−reported MSNQ scores and SDMT scores in the low EDSS (r = −.225, p = .044), but not in the medium and high EDSS groups, and significant positive correlations between MSNQ and depression in all subgroups. Conclusions: Our data suggest that the patient−report MSNQ has potential as a measure of cognition in patients with low EDSS-scores but not in the medium and high EDSS ranges.

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Section: Discussionmentioning

confidence: 99%

“…11 Regardless of its link with depression, the impact of subjective cognitive complaints in MS may be substantial, taking into consideration its associations with reduced employment and work performance, 16-17 health-related quality of life, 16 health-promoting behaviours 16,18 and reduced thalamic and cortical grey matter volumes. 19…”

Section: Introductionmentioning

confidence: 99%

Correlates of patient-reported cognitive performance with regard to disability

Laethem

Cock

Schependom

et al. 2021

Preprint

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“…Thalamic atrophy has received increasing attention as an outcome measure in clinical trials given its association with cognitive impairment, physical disability, and fatigue . Thalamic volume loss has been examined in post hoc analyses of disease modifying therapies (DMTs; fingolimod and natalizumab) and was incorporated as a secondary outcome prospectively (eg, phase III trials of ozanimod) .…”

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confidence: 99%

Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis

Mahajan

Nakamura

Cohen

et al. 2020

Annals of Neurology

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Objective Thalamic atrophy is among the earliest brain changes detected in patients with multiple sclerosis (MS) and the degree of thalamic atrophy is a strong predictor of disability progression. The causes of thalamic atrophy are not fully understood. Here, we investigate the contributions of thalamic demyelinated lesions, thalamic neuronal loss, and cerebral white matter (WM) lesions to thalamic volume. Methods We used postmortem in situ magnetic resonance imaging (MRI) scans of 95 subjects with MS to correlate thalamic lesion volumes with global MRI metrics. We histologically characterized thalamic demyelination patterns and compared neuronal loss and neuritic pathology in the thalami with the extremes of volume. Results Grossly apparent thalamic discolorations in cm‐thick brain slices were T2/fluid‐attenuated inversion recovery (FLAIR) hyperintense, T1‐hypointense, and appeared as perivascular demyelinated lesions with dystrophic neurons/axons. Subependymal demyelinated lesions with axonal loss and microglial/macrophage activation were also observed. The 12 subjects with the least thalamic volume had a 17.6% reduction of median neuronal density in the dorsomedial/ventrolateral and pulvinar nuclei compared with the 14 subjects with the greatest thalamic volume (p = 0.03). After correcting for age, disease duration, sex, and T2 lesion volume, the total (p = 0.20), ovoid (p = 0.31), or subependymal (p = 0.44) MRI thalamic lesion volumes correlated with thalamic volume. Thalamic volume correlated with cerebral T2 lesion volume (Spearman’s rho = −0.65, p < 0.001; p < 0.0001 after correcting for age, disease duration, and sex). Interpretation Our findings suggest the degeneration of efferent/afferent thalamic projections and/or a neurodegenerative process as greater contributors to thalamic atrophy than thalamic demyelinating lesions. ANN NEUROL 2020 ANN NEUROL 2020;88:81–92

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“…With the NQU, economic models can now incorporate utilities from the broad range of published studies in which patients with MS have completed the Neuro-QoL. 5,9,11,49,50 When choosing whether to use utilities derived from generic or condition-specific measures, researchers should consider the tradeoffs between these approaches. Condition-specific instruments are often thought to be more sensitive to change and disease severity because they focus on relevant constructs.…”

Section: Discussionmentioning

confidence: 99%

“…The Neuro-QoL item banks and short forms are increasingly used to assess patients with MS. [5][6][7][8][9][10][11][12] As these studies are published, the HRQL results for a wide range of patients with MS are becoming publicly available. If these Neuro-QoL scores could be converted into health state utilities, the resulting values would be useful in costutility analyses (CUAs), which are conducted to inform decisions regarding allocation of health care resources worldwide.…”

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confidence: 99%

A Scoring Algorithm for Deriving Utility Values from the Neuro-QoL for Patients with Multiple Sclerosis

et al. 2020

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Introduction The Neuro-QoL is a standardized approach to assessing health-related quality of life in people with neurological conditions, including multiple sclerosis (MS). Item banks were developed with item response theory (IRT) methodology so items are calibrated along a continuum of each construct. The purpose of this study was to develop a preference-based scoring algorithm for the Neuro-QoL to derive utilities that could be used in economic modeling. Methods With input from neurologists, 6 Neuro-QoL domains were selected based on relevance to MS and used to define health states for a utility elicitation study in the United Kingdom. General population participants and individuals with MS valued the health states and completed questionnaires (including Neuro-QoL short forms). The Neuro-QoL Utility Scoring System (NQU) was derived based on multi-attribute utility theory using data from the general population sample. Single-attribute disutility functions for 6 Neuro-QoL domains were estimated using isotonic regression with linear interpolation and then combined with a multiplicative model. NQU validity was assessed using MS participant data. Results Interviews were completed with 203 general population participants (50.2% female; mean age = 45.0 years) and 62 participants with MS (62.9% female; mean age = 46.1 years). Mean (SD) NQU scores were 0.94 (0.06) and 0.82 (0.13) for the general population and MS samples, respectively. The NQU demonstrated known-groups validity by differentiating among subgroups categorized based on level of disability. The NQU demonstrated convergent validity via correlations with generic measures (0.66 and 0.63 with EQ-5D-5L and Health Utilities Index Mark 3, respectively; both P < 0.001). Discussion With the NQU, utilities can be derived from any MS treatment group, subgroup, or patient sample who completes items from 6 Neuro-QoL domains. Because the Neuro-QoL is frequently used with MS patients, the NQU greatly expands the options for quantifying outcomes in cost-utility analyses conducted to inform allocation of resources for MS treatment.

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Subjective cognitive concern in multiple sclerosis is associated with reduced thalamic and cortical gray matter volumes

Cited by 18 publications

References 35 publications

Correlates of patient-reported cognitive performance with regard to disability

Correlates of patient-reported cognitive performance with regard to disability

Intrinsic and Extrinsic Mechanisms of Thalamic Pathology in Multiple Sclerosis

A Scoring Algorithm for Deriving Utility Values from the Neuro-QoL for Patients with Multiple Sclerosis

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