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Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities
INTRODUCTION: Similar white matter hyperintensities (WMH) burden may have varied cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study aimed to evaluate whether blood–brain barrier (BBB) permeability is associated with cognitive impairment (CI) heterogeneity in patient...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Healthcare
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444912/ https://www.ncbi.nlm.nih.gov/pubmed/37490234 http://dx.doi.org/10.1007/s40120-023-00527-z |
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author | Wang, Xing Shi, Yulu Chen, Yiyi Gao, Ying Wang, Tingting Li, Zhengyang Wang, Yilong |
author_facet | Wang, Xing Shi, Yulu Chen, Yiyi Gao, Ying Wang, Tingting Li, Zhengyang Wang, Yilong |
author_sort | Wang, Xing |
collection | PubMed |
description | INTRODUCTION: Similar white matter hyperintensities (WMH) burden may have varied cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study aimed to evaluate whether blood–brain barrier (BBB) permeability is associated with cognitive impairment (CI) heterogeneity in patients with WMH. METHODS: We recruited 51 participants with WMH. We evaluated WMH burden using the Fazekas scale and WMH volume on structural magnetic resonance imaging (MRI), and assessed BBB permeability using dynamic contrast-enhanced (DCE)-MRI. We used permeability–surface area product (PS) from the Patlak model to represent BBB permeability. All patients underwent Mini-Mental State Examination (MMSE), Boston Naming Test (BNT) and animal verbal fluency test (VFT) for cognitive assessment. We divided patients into CI and non-CI groups based on their MMSE scores (< 27 or ≥ 27) and used multiple linear regression models to investigate the associations between MRI parameters and cognitive function. RESULTS: Patients in the two groups did not differ in Fazekas scores and WMH volume. However, patients in the CI group showed significantly higher PS in the WMH regions than those in non-CI group (1.89 × 10(−3) versus 1.00 × 10(−3), p = 0.032 in periventricular WMH [PVWMH]; 1.27 × 10(−3) versus 0.74 × 10(−3), p = 0.043 in deep WMH [DWMH]), indicating the breakdown of BBB in the CI group. In all patients with WMH, increased BBB permeability in PVWMH and DWMH was significantly associated with lower cognitive and language function after adjustment for age, education level (EL) and intracranial volume (ICV). In the CI group, this correlation remained significant. WMH volume was not associated with cognitive performance in either all patients or those with CI. CONCLUSION: BBB impairment might be a more sensitive indicator for cognitive and language dysfunction than WMH volume in patients with WMH and possibly explains the heterogeneity of cognitive performance in patients with similar WMH burden. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1007/s40120-023-00527-z. |
format | Online Article Text |
id | pubmed-10444912 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Healthcare |
record_format | MEDLINE/PubMed |
spelling | pubmed-104449122023-08-24 Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities Wang, Xing Shi, Yulu Chen, Yiyi Gao, Ying Wang, Tingting Li, Zhengyang Wang, Yilong Neurol Ther Original Research INTRODUCTION: Similar white matter hyperintensities (WMH) burden may have varied cognitive outcomes in patients with cerebral small vessel disease (CSVD). This study aimed to evaluate whether blood–brain barrier (BBB) permeability is associated with cognitive impairment (CI) heterogeneity in patients with WMH. METHODS: We recruited 51 participants with WMH. We evaluated WMH burden using the Fazekas scale and WMH volume on structural magnetic resonance imaging (MRI), and assessed BBB permeability using dynamic contrast-enhanced (DCE)-MRI. We used permeability–surface area product (PS) from the Patlak model to represent BBB permeability. All patients underwent Mini-Mental State Examination (MMSE), Boston Naming Test (BNT) and animal verbal fluency test (VFT) for cognitive assessment. We divided patients into CI and non-CI groups based on their MMSE scores (< 27 or ≥ 27) and used multiple linear regression models to investigate the associations between MRI parameters and cognitive function. RESULTS: Patients in the two groups did not differ in Fazekas scores and WMH volume. However, patients in the CI group showed significantly higher PS in the WMH regions than those in non-CI group (1.89 × 10(−3) versus 1.00 × 10(−3), p = 0.032 in periventricular WMH [PVWMH]; 1.27 × 10(−3) versus 0.74 × 10(−3), p = 0.043 in deep WMH [DWMH]), indicating the breakdown of BBB in the CI group. In all patients with WMH, increased BBB permeability in PVWMH and DWMH was significantly associated with lower cognitive and language function after adjustment for age, education level (EL) and intracranial volume (ICV). In the CI group, this correlation remained significant. WMH volume was not associated with cognitive performance in either all patients or those with CI. CONCLUSION: BBB impairment might be a more sensitive indicator for cognitive and language dysfunction than WMH volume in patients with WMH and possibly explains the heterogeneity of cognitive performance in patients with similar WMH burden. SUPPLEMENTARY INFORMATION: The online version supplementary material available at 10.1007/s40120-023-00527-z. Springer Healthcare 2023-07-25 /pmc/articles/PMC10444912/ /pubmed/37490234 http://dx.doi.org/10.1007/s40120-023-00527-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by-nc/4.0/Open Access This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) . |
spellingShingle | Original Research Wang, Xing Shi, Yulu Chen, Yiyi Gao, Ying Wang, Tingting Li, Zhengyang Wang, Yilong Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title | Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title_full | Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title_fullStr | Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title_full_unstemmed | Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title_short | Blood–Brain Barrier Breakdown is a Sensitive Biomarker of Cognitive and Language Impairment in Patients with White Matter Hyperintensities |
title_sort | blood–brain barrier breakdown is a sensitive biomarker of cognitive and language impairment in patients with white matter hyperintensities |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444912/ https://www.ncbi.nlm.nih.gov/pubmed/37490234 http://dx.doi.org/10.1007/s40120-023-00527-z |
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