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Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis

IMPORTANCE: Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. OBJECTIVE: To determine wh...

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Autores principales: Abel, Shawna, Vavasour, Irene, Lee, Lisa Eunyoung, Johnson, Poljanka, Ristow, Stephen, Ackermans, Nathalie, Chan, Jillian, Cross, Helen, Laule, Cornelia, Dvorak, Adam, Schabas, Alice, Hernández-Torres, Enedino, Tam, Roger, Kuan, Annie J., Morrow, Sarah A., Wilken, Jeffrey, Rauscher, Alexander, Bhan, Virender, Sayao, Ana-Luiza, Devonshire, Virginia, Li, David K. B., Carruthers, Robert, Traboulsee, Anthony, Kolind, Shannon H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Medical Association 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525360/
https://www.ncbi.nlm.nih.gov/pubmed/32990740
http://dx.doi.org/10.1001/jamanetworkopen.2020.14220
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author Abel, Shawna
Vavasour, Irene
Lee, Lisa Eunyoung
Johnson, Poljanka
Ristow, Stephen
Ackermans, Nathalie
Chan, Jillian
Cross, Helen
Laule, Cornelia
Dvorak, Adam
Schabas, Alice
Hernández-Torres, Enedino
Tam, Roger
Kuan, Annie J.
Morrow, Sarah A.
Wilken, Jeffrey
Rauscher, Alexander
Bhan, Virender
Sayao, Ana-Luiza
Devonshire, Virginia
Li, David K. B.
Carruthers, Robert
Traboulsee, Anthony
Kolind, Shannon H.
author_facet Abel, Shawna
Vavasour, Irene
Lee, Lisa Eunyoung
Johnson, Poljanka
Ristow, Stephen
Ackermans, Nathalie
Chan, Jillian
Cross, Helen
Laule, Cornelia
Dvorak, Adam
Schabas, Alice
Hernández-Torres, Enedino
Tam, Roger
Kuan, Annie J.
Morrow, Sarah A.
Wilken, Jeffrey
Rauscher, Alexander
Bhan, Virender
Sayao, Ana-Luiza
Devonshire, Virginia
Li, David K. B.
Carruthers, Robert
Traboulsee, Anthony
Kolind, Shannon H.
author_sort Abel, Shawna
collection PubMed
description IMPORTANCE: Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. OBJECTIVE: To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019. EXPOSURES: MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS. MAIN OUTCOMES AND MEASURES: The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest—the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum—were selected a priori according to their known involvement in MS-related cognitive impairment. RESULTS: For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = −0.490; 95% CI, −0.697 to −0.284; P < .001; corpus callosum, r = −0.471; 95% CI, −0.680 to −0.262; P < .001; and cingulum, r = −0.419; 95% CI, −0.634 to −0.205; P < .001), Selective Reminding Test (SLF, r = −0.444; 95% CI, −0.660 to −0.217; P < .001; corpus callosum, r = −0.411; 95% CI, −0.630 to −0.181; P = .001; and cingulum, r = −0.361; 95% CI, −0.602 to −0.130; P = .003), and Controlled Oral Word Association Test (SLF, r = −0.317; 95% CI, −0.549 to −0.078; P = .01; and cingulum, r = −0.335; 95% CI, −0.658 to −0.113; P = .006). No significant associations were found in controls. CONCLUSIONS AND RELEVANCE: This study used MWI to demonstrate that otherwise normal-appearing brain tissue is diffusely damaged in MS, and the findings suggest that myelin water measures are associated with cognitive performance. MWI offers an in vivo biomarker feasible for use in clinical trials investigating cognition, providing a means for monitoring changes in myelination and its association with symptom worsening or improvement.
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spelling pubmed-75253602020-10-05 Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis Abel, Shawna Vavasour, Irene Lee, Lisa Eunyoung Johnson, Poljanka Ristow, Stephen Ackermans, Nathalie Chan, Jillian Cross, Helen Laule, Cornelia Dvorak, Adam Schabas, Alice Hernández-Torres, Enedino Tam, Roger Kuan, Annie J. Morrow, Sarah A. Wilken, Jeffrey Rauscher, Alexander Bhan, Virender Sayao, Ana-Luiza Devonshire, Virginia Li, David K. B. Carruthers, Robert Traboulsee, Anthony Kolind, Shannon H. JAMA Netw Open Original Investigation IMPORTANCE: Cognitive impairment is a debilitating symptom of multiple sclerosis (MS) that affects up to 70% of patients. An improved understanding of the underlying pathology of MS-related cognitive impairment would provide considerable benefit to patients and clinicians. OBJECTIVE: To determine whether there is an association between myelin damage in tissue that appears completely normal on standard clinical imaging, but can be detected by myelin water imaging (MWI), with cognitive performance in MS. DESIGN, SETTING, AND PARTICIPANTS: In this cross-sectional study, participants with MS and controls underwent cognitive testing and magnetic resonance imaging (MRI) from August 23, 2017, to February 20, 2019. Participants were recruited through the University of British Columbia Hospital MS clinic and via online recruitment advertisements on local health authority websites. Cognitive testing was performed in the MS clinic, and MRI was performed at the adjacent academic research neuroimaging center. Seventy-three participants with clinically definite MS fulfilling the 2017 revised McDonald criteria for diagnosis and 22 age-, sex-, and education-matched healthy volunteers without neurological disease were included in the study. Data analysis was performed from March to November 2019. EXPOSURES: MWI was performed at 3 T with a 48-echo, 3-dimensional, gradient and spin-echo (GRASE) sequence. Cognitive testing was performed with assessments drawn from cognitive batteries validated for use in MS. MAIN OUTCOMES AND MEASURES: The association between myelin water measures, a measurement of the T2 relaxation signal from water in the myelin bilayers providing a specific marker for myelin, and cognitive test scores was assessed using Pearson correlation. Three white matter regions of interest—the cingulum, superior longitudinal fasciculus (SLF), and corpus callosum—were selected a priori according to their known involvement in MS-related cognitive impairment. RESULTS: For the 95 total participants, the mean (SD) age was 49.33 (11.44) years. The mean (SD) age was 50.2 (10.7) years for the 73 participants with MS and 46.4 (13.5) for the 22 controls. Forty-eight participants with MS (66%) and 14 controls (64%) were women. The mean (SD) years of education were 14.7 (2.2) for patients and 15.8 (2.5) years for controls. In MS, significant associations were observed between myelin water measures and scores on the Symbol Digit Modalities Test (SLF, r = −0.490; 95% CI, −0.697 to −0.284; P < .001; corpus callosum, r = −0.471; 95% CI, −0.680 to −0.262; P < .001; and cingulum, r = −0.419; 95% CI, −0.634 to −0.205; P < .001), Selective Reminding Test (SLF, r = −0.444; 95% CI, −0.660 to −0.217; P < .001; corpus callosum, r = −0.411; 95% CI, −0.630 to −0.181; P = .001; and cingulum, r = −0.361; 95% CI, −0.602 to −0.130; P = .003), and Controlled Oral Word Association Test (SLF, r = −0.317; 95% CI, −0.549 to −0.078; P = .01; and cingulum, r = −0.335; 95% CI, −0.658 to −0.113; P = .006). No significant associations were found in controls. CONCLUSIONS AND RELEVANCE: This study used MWI to demonstrate that otherwise normal-appearing brain tissue is diffusely damaged in MS, and the findings suggest that myelin water measures are associated with cognitive performance. MWI offers an in vivo biomarker feasible for use in clinical trials investigating cognition, providing a means for monitoring changes in myelination and its association with symptom worsening or improvement. American Medical Association 2020-09-29 /pmc/articles/PMC7525360/ /pubmed/32990740 http://dx.doi.org/10.1001/jamanetworkopen.2020.14220 Text en Copyright 2020 Abel S et al. JAMA Network Open. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the CC-BY License.
spellingShingle Original Investigation
Abel, Shawna
Vavasour, Irene
Lee, Lisa Eunyoung
Johnson, Poljanka
Ristow, Stephen
Ackermans, Nathalie
Chan, Jillian
Cross, Helen
Laule, Cornelia
Dvorak, Adam
Schabas, Alice
Hernández-Torres, Enedino
Tam, Roger
Kuan, Annie J.
Morrow, Sarah A.
Wilken, Jeffrey
Rauscher, Alexander
Bhan, Virender
Sayao, Ana-Luiza
Devonshire, Virginia
Li, David K. B.
Carruthers, Robert
Traboulsee, Anthony
Kolind, Shannon H.
Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title_full Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title_fullStr Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title_full_unstemmed Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title_short Associations Between Findings From Myelin Water Imaging and Cognitive Performance Among Individuals With Multiple Sclerosis
title_sort associations between findings from myelin water imaging and cognitive performance among individuals with multiple sclerosis
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525360/
https://www.ncbi.nlm.nih.gov/pubmed/32990740
http://dx.doi.org/10.1001/jamanetworkopen.2020.14220
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