Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis

Rocca, Maria A.; Amato, Maria Pia; Stefano, Nicola De; Enzinger, Christian; Geurts, Jeroen J. G.; Penner, Iris‐Katharina; Rovira, Àlex; Sumowski, James F.; Valsasina, Paola; Filippi, Massimo

doi:10.1016/s1474-4422(14)70250-9

Cited by 464 publications

(481 citation statements)

References 136 publications

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“…This could be a result of our sample consisting of predominantly patients with a short disease duration and low disease burden. Another limitation is that focal MRI lesions of white matter are only partially reflective of the disseminated pathology in MS 3, 10, 11. Their specific topography rather than volume may play a role in the pathogenesis of cognitive impairment.…”

Section: Discussionmentioning

confidence: 99%

“…Their specific topography rather than volume may play a role in the pathogenesis of cognitive impairment. More sophisticated nonconventional MRI techniques, such as magnetization transfer ratio, diffusion tensor imaging, proton MRI spectroscopy, and functional MRI measuring various aspects of MS pathology,3 are likely to further improve our understanding of the associations between MRI and cognitive function at different stages of MS. Finally, sufficiently powered longitudinal studies are warranted to investigate the long‐term associations between MRI and cognitive changes.…”

Section: Discussionmentioning

confidence: 99%

“…The clinical presentation of multiple sclerosis (MS) includes a wide range of physical, as well as cognitive, signs, and symptoms 1, 2, 3, 4. In particular, cognitive impairment has recently been increasingly recognized as an important determinant of employment status and associated societal costs,5, 6 negatively impacting social functioning, coping, quality of life, and treatment adherence among patients with MS 7…”

Section: Introductionmentioning

confidence: 99%

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Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Uher

Krásenský

Sobíšek

et al. 2017

Ann Clin Transl Neurol

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ObjectiveTo investigate whether the strength of the association between magnetic resonance imaging (MRI) metrics and cognitive outcomes differs between various multiple sclerosis subpopulations.MethodsA total of 1052 patients were included in this large cross‐sectional study. Brain MRI (T1 and T2 lesion volume and brain parenchymal fraction) and neuropsychological assessment (Brief International Cognitive Assessment for Multiple Sclerosis and Paced Auditory Serial Addition Test) were performed.ResultsWeak correlations between cognitive domains and MRI measures were observed in younger patients (age≤30 years; absolute Spearman's rho = 0.05–0.21), with short disease duration (<2 years; rho = 0.01–0.21), low Expanded Disability Status Scale [EDSS] (≤1.5; rho = 0.08–0.18), low T2 lesion volume (lowest quartile; <0.59 mL; rho = 0.01–0.20), and high brain parenchymal fraction (highest quartile; >86.66; rho = 0.01–0.16). Stronger correlations between cognitive domains and MRI measures were observed in older patients (age>50 years; rho = 0.24–0.50), with longer disease duration (>15 years; rho = 0.26–0.53), higher EDSS (≥5.0; rho = 0.23–0.39), greater T2 lesion volume (highest quartile; >5.33 mL; rho = 0.16–0.32), and lower brain parenchymal fraction (lowest quartile; <83.71; rho = 0.13–0.46). The majority of these observed results were confirmed by significant interactions (P ≤ 0.01) using continuous variables.InterpretationThe association between structural brain damage and functional cognitive impairment is substantially weaker in multiple sclerosis patients with a low disease burden. Therefore, disease stage should be taken into consideration when interpreting associations between structural and cognitive measures in clinical trials, research studies, and clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Uher

Krásenský

Sobíšek

et al. 2017

Ann Clin Transl Neurol

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“…With increasing T2‐lesion load, the loss of network efficiency is more pronounced in the insula than in other regions (He et al., 2009). Based on several structural and functional MRI studies, inefficient task assignment and recruitment strategies are an established concept to explain cognitive impairment in MS (Rocca et al., 2015). The association between retinal thickness and insula volume in our cohort was considerably robust as findings were reproducible in the whole cohort including patients with previous optic neuritis as well after correcting for T2‐lesion volume and multiple testing.…”

Section: Discussionmentioning

confidence: 99%

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing–remitting MS

et al. 2016

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BackgroundNeurodegeneration in multiple sclerosis (MS) may be investigated in the visual system as optical coherence tomography (OCT) and magnetic resonance imaging (MRI) allows examining structural integrity in detail. The association between thickness of retinal layers and focal cortical volumes beyond the primary visual system has not been thoroughly investigated.ObjectiveTo investigate the association between focal cortical volume and thickness of retinal layers.MethodsFifty‐four patients (relapsing–remitting MS, mean age 40.5 years, mean disease duration 7.6 years, median EDSS 2) underwent OCT and MRI. The association between focal cortical volume and OCT measurements was investigated with voxel‐based morphometry (VBM). Patterns of association were determined with Yeo's functional network atlas and the Harvard‐Oxford cortical atlas. We used GEE models with cortical volumes from the FreeSurfer parcellation to confirm VBM results. Post hoc, we analyzed the association between OCT, focal cortical volumes, and an extended neuropsychological assessment in a subgroup of 14 patients.ResultsMacular retinal nerve fiber layer (mRNFL) and ganglion cell /inner plexiform layer (GCIPL) showed a robust association with mainly the insular cortex and the cingulate cortex. VBM findings were confirmed with FreeSurfer volumes. The post hoc analysis detected significant correlations between both OCT outcomes and cognition.ConclusionBesides the primary visual system, OCT outcomes show a correlation pattern with cortical regions that are known to be important for cognitive performance, predominantly the insula in both hemispheres. Thus, OCT should be further investigated as a marker for neurodegeneration in MS.

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“…Cognitive deterioration is common in multiple sclerosis (MS) (Chiaravalloti & DeLuca 2008), but poorly understood (Benedict & Zivadinov 2011; Rocca et al, 2015a). Previous functional imaging studies in MS hypothesized that a process called “functional reorganization” compensates for accumulating structural damage before the functional network collapses, leading to inadvertent cognitive decline (Schoonheim, Meijer, & Geurts, 2015b).…”

Section: Introductionmentioning

confidence: 99%

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study

Tewarie

Steenwijk

Brookes

et al. 2018

Human Brain Mapping

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To understand the heterogeneity of functional connectivity results reported in the literature, we analyzed the separate effects of grey and white matter damage on functional connectivity and networks in multiple sclerosis. For this, we employed a biophysical thalamo‐cortical model consisting of interconnected cortical and thalamic neuronal populations, informed and amended by empirical diffusion MRI tractography data, to simulate functional data that mimic neurophysiological signals. Grey matter degeneration was simulated by decreasing within population connections and white matter degeneration by lowering between population connections, based on lesion predilection sites in multiple sclerosis. For all simulations, functional connectivity and functional network organization are quantified by phase synchronization and network integration, respectively. Modeling results showed that both cortical and thalamic grey matter damage induced a global increase in functional connectivity, whereas white matter damage induced an initially increased connectivity followed by a global decrease. Both white and especially grey matter damage, however, induced a decrease in network integration. These empirically informed simulations show that specific topology and timing of structural damage are nontrivial aspects in explaining functional abnormalities in MS. Insufficient attention to these aspects likely explains contradictory findings in multiple sclerosis functional imaging studies so far.

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Clinical and imaging assessment of cognitive dysfunction in multiple sclerosis

Cited by 464 publications

References 136 publications

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Cognitive clinico‐radiological paradox in early stages of multiple sclerosis

Pattern of gray matter volumes related to retinal thickness and its association with cognitive function in relapsing–remitting MS

Explaining the heterogeneity of functional connectivity findings in multiple sclerosis: An empirically informed modeling study

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