Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease
Abstract The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnorm...
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| Veröffentlicht in: | Brain (London, England : 1878) England : 1878), 2023-11, Vol.146 (11), p.4659-4673 |
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| creator | Li, Hao Jacob, Mina A Cai, Mengfei Duering, Marco Chamberland, Maxime Norris, David G Kessels, Roy P C de Leeuw, Frank-Erik Marques, José P Tuladhar, Anil M |
| description | Abstract
The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions.
In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts.
We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = −0.30, Pcorrected < 0.001), lower R1 (β = −0.26, Pcorrected = 0.001), lower R2* (β = −0.32, Pcorrected < 0.001) and lower susceptibility values (β = −0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions.
Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iro |
| doi_str_mv | 10.1093/brain/awad220 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_10629800</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/brain/awad220</oup_id><sourcerecordid>2830216742</sourcerecordid><originalsourceid>FETCH-LOGICAL-c421t-1a31a26c627998a514722f04d58c03e5cb716d75c8a721db6919a3d1131fb3053</originalsourceid><addsrcrecordid>eNqFkc2LFDEQxYMo7rh69Co5erDdqqQ73X0SWdYPWBBEwVuoTmpmI-n0mPSs7H9vdMdVT56qoH68V7wnxFOElwijPpsyhXRG38krBffEBlsDjcLO3BcbADDNMHZwIh6V8hUAW63MQ3Gie22M1sNGfPnIu7AkitIteQ2uLutVSCmk3Qvpeb7hGBKtFZGUvAy5LnEpRYYkHWeu9lGWmWKU11wKR-lDYSr8WDzYUiz85DhPxec3F5_O3zWXH96-P3992bhW4dogaSRlnFH9OA7UYdsrtYXWd4MDzZ2bejS-79xAvUI_mRFH0h5R43bS0OlT8epWd3-YZvaO01pfsvscZso3dqFg_72kcGV3y7VFMGocAKrC86NCXr4duKx2DsVxjJR4ORSrBg0KTd-qija3qMs1g8zbOx8E-7MO-6sOe6yj8s_-fu6O_p3_H-_lsP-P1g9cspa4</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2830216742</pqid></control><display><type>article</type><title>Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease</title><source>MEDLINE</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Li, Hao ; Jacob, Mina A ; Cai, Mengfei ; Duering, Marco ; Chamberland, Maxime ; Norris, David G ; Kessels, Roy P C ; de Leeuw, Frank-Erik ; Marques, José P ; Tuladhar, Anil M</creator><creatorcontrib>Li, Hao ; Jacob, Mina A ; Cai, Mengfei ; Duering, Marco ; Chamberland, Maxime ; Norris, David G ; Kessels, Roy P C ; de Leeuw, Frank-Erik ; Marques, José P ; Tuladhar, Anil M</creatorcontrib><description>Abstract
The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions.
In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts.
We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = −0.30, Pcorrected < 0.001), lower R1 (β = −0.26, Pcorrected = 0.001), lower R2* (β = −0.32, Pcorrected < 0.001) and lower susceptibility values (β = −0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions.
Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.
Using neuroimaging, Li et al. reveal reductions in cortical thickness, myelin, and iron in cortex connected to white matter hyperintensities in cerebral small vessel disease. These regional cortical abnormalities are associated with reduced microstructural integrity of the white matter tracts and contribute to impairments in processing speed.</description><identifier>ISSN: 0006-8950</identifier><identifier>ISSN: 1460-2156</identifier><identifier>EISSN: 1460-2156</identifier><identifier>DOI: 10.1093/brain/awad220</identifier><identifier>PMID: 37366338</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Cerebral Cortical Thinning ; Cerebral Small Vessel Diseases - complications ; Cerebral Small Vessel Diseases - diagnostic imaging ; Cerebral Small Vessel Diseases - psychology ; Cognition Disorders ; Cross-Sectional Studies ; Demyelinating Diseases - diagnostic imaging ; Humans ; Magnetic Resonance Imaging - methods ; Original ; White Matter - diagnostic imaging</subject><ispartof>Brain (London, England : 1878), 2023-11, Vol.146 (11), p.4659-4673</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of the Guarantors of Brain.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c421t-1a31a26c627998a514722f04d58c03e5cb716d75c8a721db6919a3d1131fb3053</citedby><cites>FETCH-LOGICAL-c421t-1a31a26c627998a514722f04d58c03e5cb716d75c8a721db6919a3d1131fb3053</cites><orcidid>0000-0002-2125-9092 ; 0000-0003-2302-3136</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1583,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37366338$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Jacob, Mina A</creatorcontrib><creatorcontrib>Cai, Mengfei</creatorcontrib><creatorcontrib>Duering, Marco</creatorcontrib><creatorcontrib>Chamberland, Maxime</creatorcontrib><creatorcontrib>Norris, David G</creatorcontrib><creatorcontrib>Kessels, Roy P C</creatorcontrib><creatorcontrib>de Leeuw, Frank-Erik</creatorcontrib><creatorcontrib>Marques, José P</creatorcontrib><creatorcontrib>Tuladhar, Anil M</creatorcontrib><title>Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease</title><title>Brain (London, England : 1878)</title><addtitle>Brain</addtitle><description>Abstract
The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions.
In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts.
We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = −0.30, Pcorrected < 0.001), lower R1 (β = −0.26, Pcorrected = 0.001), lower R2* (β = −0.32, Pcorrected < 0.001) and lower susceptibility values (β = −0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions.
Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.
Using neuroimaging, Li et al. reveal reductions in cortical thickness, myelin, and iron in cortex connected to white matter hyperintensities in cerebral small vessel disease. These regional cortical abnormalities are associated with reduced microstructural integrity of the white matter tracts and contribute to impairments in processing speed.</description><subject>Cerebral Cortical Thinning</subject><subject>Cerebral Small Vessel Diseases - complications</subject><subject>Cerebral Small Vessel Diseases - diagnostic imaging</subject><subject>Cerebral Small Vessel Diseases - psychology</subject><subject>Cognition Disorders</subject><subject>Cross-Sectional Studies</subject><subject>Demyelinating Diseases - diagnostic imaging</subject><subject>Humans</subject><subject>Magnetic Resonance Imaging - methods</subject><subject>Original</subject><subject>White Matter - diagnostic imaging</subject><issn>0006-8950</issn><issn>1460-2156</issn><issn>1460-2156</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><sourceid>EIF</sourceid><recordid>eNqFkc2LFDEQxYMo7rh69Co5erDdqqQ73X0SWdYPWBBEwVuoTmpmI-n0mPSs7H9vdMdVT56qoH68V7wnxFOElwijPpsyhXRG38krBffEBlsDjcLO3BcbADDNMHZwIh6V8hUAW63MQ3Gie22M1sNGfPnIu7AkitIteQ2uLutVSCmk3Qvpeb7hGBKtFZGUvAy5LnEpRYYkHWeu9lGWmWKU11wKR-lDYSr8WDzYUiz85DhPxec3F5_O3zWXH96-P3992bhW4dogaSRlnFH9OA7UYdsrtYXWd4MDzZ2bejS-79xAvUI_mRFH0h5R43bS0OlT8epWd3-YZvaO01pfsvscZso3dqFg_72kcGV3y7VFMGocAKrC86NCXr4duKx2DsVxjJR4ORSrBg0KTd-qija3qMs1g8zbOx8E-7MO-6sOe6yj8s_-fu6O_p3_H-_lsP-P1g9cspa4</recordid><startdate>20231102</startdate><enddate>20231102</enddate><creator>Li, Hao</creator><creator>Jacob, Mina A</creator><creator>Cai, Mengfei</creator><creator>Duering, Marco</creator><creator>Chamberland, Maxime</creator><creator>Norris, David G</creator><creator>Kessels, Roy P C</creator><creator>de Leeuw, Frank-Erik</creator><creator>Marques, José P</creator><creator>Tuladhar, Anil M</creator><general>Oxford University Press</general><scope>TOX</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2125-9092</orcidid><orcidid>https://orcid.org/0000-0003-2302-3136</orcidid></search><sort><creationdate>20231102</creationdate><title>Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease</title><author>Li, Hao ; Jacob, Mina A ; Cai, Mengfei ; Duering, Marco ; Chamberland, Maxime ; Norris, David G ; Kessels, Roy P C ; de Leeuw, Frank-Erik ; Marques, José P ; Tuladhar, Anil M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c421t-1a31a26c627998a514722f04d58c03e5cb716d75c8a721db6919a3d1131fb3053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Cerebral Cortical Thinning</topic><topic>Cerebral Small Vessel Diseases - complications</topic><topic>Cerebral Small Vessel Diseases - diagnostic imaging</topic><topic>Cerebral Small Vessel Diseases - psychology</topic><topic>Cognition Disorders</topic><topic>Cross-Sectional Studies</topic><topic>Demyelinating Diseases - diagnostic imaging</topic><topic>Humans</topic><topic>Magnetic Resonance Imaging - methods</topic><topic>Original</topic><topic>White Matter - diagnostic imaging</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Hao</creatorcontrib><creatorcontrib>Jacob, Mina A</creatorcontrib><creatorcontrib>Cai, Mengfei</creatorcontrib><creatorcontrib>Duering, Marco</creatorcontrib><creatorcontrib>Chamberland, Maxime</creatorcontrib><creatorcontrib>Norris, David G</creatorcontrib><creatorcontrib>Kessels, Roy P C</creatorcontrib><creatorcontrib>de Leeuw, Frank-Erik</creatorcontrib><creatorcontrib>Marques, José P</creatorcontrib><creatorcontrib>Tuladhar, Anil M</creatorcontrib><collection>Oxford Journals Open Access Collection</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Brain (London, England : 1878)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Hao</au><au>Jacob, Mina A</au><au>Cai, Mengfei</au><au>Duering, Marco</au><au>Chamberland, Maxime</au><au>Norris, David G</au><au>Kessels, Roy P C</au><au>de Leeuw, Frank-Erik</au><au>Marques, José P</au><au>Tuladhar, Anil M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease</atitle><jtitle>Brain (London, England : 1878)</jtitle><addtitle>Brain</addtitle><date>2023-11-02</date><risdate>2023</risdate><volume>146</volume><issue>11</issue><spage>4659</spage><epage>4673</epage><pages>4659-4673</pages><issn>0006-8950</issn><issn>1460-2156</issn><eissn>1460-2156</eissn><abstract>Abstract
The link between white matter hyperintensities (WMH) and cortical thinning is thought to be an important pathway by which WMH contributes to cognitive deficits in cerebral small vessel disease (SVD). However, the mechanism behind this association and the underlying tissue composition abnormalities are unclear. The objective of this study is to determine the association between WMH and cortical thickness, and the in vivo tissue composition abnormalities in the WMH-connected cortical regions.
In this cross-sectional study, we included 213 participants with SVD who underwent standardized protocol including multimodal neuroimaging scans and cognitive assessment (i.e. processing speed, executive function and memory). We identified the cortex connected to WMH using probabilistic tractography starting from the WMH and defined the WMH-connected regions at three connectivity levels (low, medium and high connectivity level). We calculated the cortical thickness, myelin and iron of the cortex based on T1-weighted, quantitative R1, R2* and susceptibility maps. We used diffusion-weighted imaging to estimate the mean diffusivity of the connecting white matter tracts.
We found that cortical thickness, R1, R2* and susceptibility values in the WMH-connected regions were significantly lower than in the WMH-unconnected regions (all Pcorrected < 0.001). Linear regression analyses showed that higher mean diffusivity of the connecting white matter tracts were related to lower thickness (β = −0.30, Pcorrected < 0.001), lower R1 (β = −0.26, Pcorrected = 0.001), lower R2* (β = −0.32, Pcorrected < 0.001) and lower susceptibility values (β = −0.39, Pcorrected < 0.001) of WMH-connected cortical regions at high connectivity level. In addition, lower scores on processing speed were significantly related to lower cortical thickness (β = 0.20, Pcorrected = 0.030), lower R1 values (β = 0.20, Pcorrected = 0.006), lower R2* values (β = 0.29, Pcorrected = 0.006) and lower susceptibility values (β = 0.19, Pcorrected = 0.024) of the WMH-connected regions at high connectivity level, independent of WMH volumes and the cortical measures of WMH-unconnected regions.
Together, our study demonstrated that the microstructural integrity of white matter tracts passing through WMH is related to the regional cortical abnormalities as measured by thickness, R1, R2* and susceptibility values in the connected cortical regions. These findings are indicative of cortical thinning, demyelination and iron loss in the cortex, which is most likely through the disruption of the connecting white matter tracts and may contribute to processing speed impairment in SVD, a key clinical feature of SVD. These findings may have implications for finding intervention targets for the treatment of cognitive impairment in SVD by preventing secondary degeneration.
Using neuroimaging, Li et al. reveal reductions in cortical thickness, myelin, and iron in cortex connected to white matter hyperintensities in cerebral small vessel disease. These regional cortical abnormalities are associated with reduced microstructural integrity of the white matter tracts and contribute to impairments in processing speed.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>37366338</pmid><doi>10.1093/brain/awad220</doi><tpages>15</tpages><orcidid>https://orcid.org/0000-0002-2125-9092</orcidid><orcidid>https://orcid.org/0000-0003-2302-3136</orcidid><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Cerebral Cortical Thinning Cerebral Small Vessel Diseases - complications Cerebral Small Vessel Diseases - diagnostic imaging Cerebral Small Vessel Diseases - psychology Cognition Disorders Cross-Sectional Studies Demyelinating Diseases - diagnostic imaging Humans Magnetic Resonance Imaging - methods Original White Matter - diagnostic imaging |
| title | Regional cortical thinning, demyelination and iron loss in cerebral small vessel disease |
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