Interplay of White Matter Hyperintensities, Cerebral Networks, and Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the Maastricht Study

Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise...

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Veröffentlicht in:Radiology 2021-02, Vol.298 (2), p.384-392
Hauptverfasser: Vergoossen, Laura W M, Jansen, Jacobus F A, van Sloten, Thomas T, Stehouwer, Coen D A, Schaper, Nicolaas C, Wesselius, Anke, Dagnelie, Pieter C, Köhler, Sebastiaan, van Boxtel, Martin P J, Kroon, Abraham A, de Jong, Joost J A, Schram, Miranda T, Backes, Walter H
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container_end_page 392
container_issue 2
container_start_page 384
container_title Radiology
container_volume 298
creator Vergoossen, Laura W M
Jansen, Jacobus F A
van Sloten, Thomas T
Stehouwer, Coen D A
Schaper, Nicolaas C
Wesselius, Anke
Dagnelie, Pieter C
Köhler, Sebastiaan
van Boxtel, Martin P J
Kroon, Abraham A
de Jong, Joost J A
Schram, Miranda T
Backes, Walter H
description Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism. Purpose To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function. Materials and Methods In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors. Results A total of 5083 participants (mean age, 59 years ± 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized β coefficient, 0.065; < .001), but not global, network efficiency and lower information processing speed (standardized β coefficient, -0.073; < .001). Moreover, lower local efficiency (standardized β coefficient, -0.084; < .001) was associated with lower information processing speed. In particular, the relationship between WMHs and information processing speed was mediated (percentage mediated, 7.2% [95% CI: 3.5, 10.9]; < .05) by the local network efficiency. Finally, WMH load was larger in the white matter tracts important for information processing speed. Conclusion White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. © RSNA, 2020
doi_str_mv 10.1148/RADIOL.2021202634
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However, there is no consensus yet about the precise underlying topological mechanism. Purpose To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function. Materials and Methods In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors. Results A total of 5083 participants (mean age, 59 years ± 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized β coefficient, 0.065; &lt; .001), but not global, network efficiency and lower information processing speed (standardized β coefficient, -0.073; &lt; .001). Moreover, lower local efficiency (standardized β coefficient, -0.084; &lt; .001) was associated with lower information processing speed. In particular, the relationship between WMHs and information processing speed was mediated (percentage mediated, 7.2% [95% CI: 3.5, 10.9]; &lt; .05) by the local network efficiency. Finally, WMH load was larger in the white matter tracts important for information processing speed. Conclusion White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. © RSNA, 2020</description><identifier>ISSN: 0033-8419</identifier><identifier>EISSN: 1527-1315</identifier><identifier>DOI: 10.1148/RADIOL.2021202634</identifier><identifier>PMID: 33350892</identifier><language>eng</language><publisher>United States</publisher><subject>Adult ; Aged ; Cognition ; Cognitive Dysfunction - physiopathology ; Diffusion Tensor Imaging - methods ; Female ; Humans ; Male ; Middle Aged ; Neural Pathways - diagnostic imaging ; Neural Pathways - physiopathology ; Prospective Studies ; White Matter - diagnostic imaging ; White Matter - physiopathology</subject><ispartof>Radiology, 2021-02, Vol.298 (2), p.384-392</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c344t-182f48dba1cd3ff5eb288547aa4abff25b4f6839f9a1409aee924d4d13d66c613</citedby><cites>FETCH-LOGICAL-c344t-182f48dba1cd3ff5eb288547aa4abff25b4f6839f9a1409aee924d4d13d66c613</cites><orcidid>0000-0002-5819-0615 ; 0000-0003-2870-482X ; 0000-0002-5271-8060 ; 0000-0001-8752-3223 ; 0000-0002-2128-8029 ; 0000-0002-2398-0609 ; 0000-0001-8113-7604 ; 0000-0001-7750-8249 ; 0000-0002-3221-2150 ; 0000-0003-4474-9665 ; 0000-0003-1767-8814 ; 0000-0001-7905-0681 ; 0000-0003-4469-0763</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,4016,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33350892$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vergoossen, Laura W M</creatorcontrib><creatorcontrib>Jansen, Jacobus F A</creatorcontrib><creatorcontrib>van Sloten, Thomas T</creatorcontrib><creatorcontrib>Stehouwer, Coen D A</creatorcontrib><creatorcontrib>Schaper, Nicolaas C</creatorcontrib><creatorcontrib>Wesselius, Anke</creatorcontrib><creatorcontrib>Dagnelie, Pieter C</creatorcontrib><creatorcontrib>Köhler, Sebastiaan</creatorcontrib><creatorcontrib>van Boxtel, Martin P J</creatorcontrib><creatorcontrib>Kroon, Abraham A</creatorcontrib><creatorcontrib>de Jong, Joost J A</creatorcontrib><creatorcontrib>Schram, Miranda T</creatorcontrib><creatorcontrib>Backes, Walter H</creatorcontrib><title>Interplay of White Matter Hyperintensities, Cerebral Networks, and Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the Maastricht Study</title><title>Radiology</title><addtitle>Radiology</addtitle><description>Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism. Purpose To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function. Materials and Methods In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors. Results A total of 5083 participants (mean age, 59 years ± 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized β coefficient, 0.065; &lt; .001), but not global, network efficiency and lower information processing speed (standardized β coefficient, -0.073; &lt; .001). Moreover, lower local efficiency (standardized β coefficient, -0.084; &lt; .001) was associated with lower information processing speed. In particular, the relationship between WMHs and information processing speed was mediated (percentage mediated, 7.2% [95% CI: 3.5, 10.9]; &lt; .05) by the local network efficiency. Finally, WMH load was larger in the white matter tracts important for information processing speed. 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Jansen, Jacobus F A ; van Sloten, Thomas T ; Stehouwer, Coen D A ; Schaper, Nicolaas C ; Wesselius, Anke ; Dagnelie, Pieter C ; Köhler, Sebastiaan ; van Boxtel, Martin P J ; Kroon, Abraham A ; de Jong, Joost J A ; Schram, Miranda T ; Backes, Walter H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c344t-182f48dba1cd3ff5eb288547aa4abff25b4f6839f9a1409aee924d4d13d66c613</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Cognition</topic><topic>Cognitive Dysfunction - physiopathology</topic><topic>Diffusion Tensor Imaging - methods</topic><topic>Female</topic><topic>Humans</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Neural Pathways - diagnostic imaging</topic><topic>Neural Pathways - physiopathology</topic><topic>Prospective Studies</topic><topic>White Matter - diagnostic imaging</topic><topic>White Matter - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vergoossen, Laura W M</creatorcontrib><creatorcontrib>Jansen, Jacobus F A</creatorcontrib><creatorcontrib>van Sloten, Thomas T</creatorcontrib><creatorcontrib>Stehouwer, Coen D A</creatorcontrib><creatorcontrib>Schaper, Nicolaas C</creatorcontrib><creatorcontrib>Wesselius, Anke</creatorcontrib><creatorcontrib>Dagnelie, Pieter C</creatorcontrib><creatorcontrib>Köhler, Sebastiaan</creatorcontrib><creatorcontrib>van Boxtel, Martin P J</creatorcontrib><creatorcontrib>Kroon, Abraham A</creatorcontrib><creatorcontrib>de Jong, Joost J A</creatorcontrib><creatorcontrib>Schram, Miranda T</creatorcontrib><creatorcontrib>Backes, Walter H</creatorcontrib><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><jtitle>Radiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vergoossen, Laura W M</au><au>Jansen, Jacobus F A</au><au>van Sloten, Thomas T</au><au>Stehouwer, Coen D A</au><au>Schaper, Nicolaas C</au><au>Wesselius, Anke</au><au>Dagnelie, Pieter C</au><au>Köhler, Sebastiaan</au><au>van Boxtel, Martin P J</au><au>Kroon, Abraham A</au><au>de Jong, Joost J A</au><au>Schram, Miranda T</au><au>Backes, Walter H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interplay of White Matter Hyperintensities, Cerebral Networks, and Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the Maastricht Study</atitle><jtitle>Radiology</jtitle><addtitle>Radiology</addtitle><date>2021-02</date><risdate>2021</risdate><volume>298</volume><issue>2</issue><spage>384</spage><epage>392</epage><pages>384-392</pages><issn>0033-8419</issn><eissn>1527-1315</eissn><abstract>Background Lesions of cerebral small vessel disease, such as white matter hyperintensities (WMHs) in individuals with cardiometabolic risk factors, interfere with the trajectories of the white matter and eventually contribute to cognitive decline. However, there is no consensus yet about the precise underlying topological mechanism. Purpose To examine whether WMH and cognitive function are associated and whether any such association is mediated or explained by structural connectivity measures in an adult population. In addition, to investigate underlying local abnormalities in white matter by assessing the tract-specific WMH volumes and their tract-specific association with cognitive function. Materials and Methods In the prospective type 2 diabetes-enriched population-based Maastricht Study, structural and diffusion-tensor MRI was performed (December 2013 to February 2017). Total and tract-specific WMH volumes; network measures; cognition scores; and demographic, cardiovascular, and lifestyle characteristics were determined. Multivariable linear regression and mediation analyses were used to investigate the association of WMH volume, tract-specific WMH volumes, and network measures with cognitive function. Associations were adjusted for age, sex, education, diabetes status, and cardiovascular risk factors. Results A total of 5083 participants (mean age, 59 years ± 9 [standard deviation]; 2592 men; 1027 with diabetes) were evaluated. Larger WMH volumes were associated with stronger local (standardized β coefficient, 0.065; &lt; .001), but not global, network efficiency and lower information processing speed (standardized β coefficient, -0.073; &lt; .001). Moreover, lower local efficiency (standardized β coefficient, -0.084; &lt; .001) was associated with lower information processing speed. In particular, the relationship between WMHs and information processing speed was mediated (percentage mediated, 7.2% [95% CI: 3.5, 10.9]; &lt; .05) by the local network efficiency. Finally, WMH load was larger in the white matter tracts important for information processing speed. Conclusion White matter hyperintensity volume, local network efficiency, and information processing speed scores are interrelated, and local network properties explain lower cognitive performance due to white matter network alterations. © RSNA, 2020</abstract><cop>United States</cop><pmid>33350892</pmid><doi>10.1148/RADIOL.2021202634</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-5819-0615</orcidid><orcidid>https://orcid.org/0000-0003-2870-482X</orcidid><orcidid>https://orcid.org/0000-0002-5271-8060</orcidid><orcidid>https://orcid.org/0000-0001-8752-3223</orcidid><orcidid>https://orcid.org/0000-0002-2128-8029</orcidid><orcidid>https://orcid.org/0000-0002-2398-0609</orcidid><orcidid>https://orcid.org/0000-0001-8113-7604</orcidid><orcidid>https://orcid.org/0000-0001-7750-8249</orcidid><orcidid>https://orcid.org/0000-0002-3221-2150</orcidid><orcidid>https://orcid.org/0000-0003-4474-9665</orcidid><orcidid>https://orcid.org/0000-0003-1767-8814</orcidid><orcidid>https://orcid.org/0000-0001-7905-0681</orcidid><orcidid>https://orcid.org/0000-0003-4469-0763</orcidid><oa>free_for_read</oa></addata></record>
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subjects Adult
Aged
Cognition
Cognitive Dysfunction - physiopathology
Diffusion Tensor Imaging - methods
Female
Humans
Male
Middle Aged
Neural Pathways - diagnostic imaging
Neural Pathways - physiopathology
Prospective Studies
White Matter - diagnostic imaging
White Matter - physiopathology
title Interplay of White Matter Hyperintensities, Cerebral Networks, and Cognitive Function in an Adult Population: Diffusion-Tensor Imaging in the Maastricht Study
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