Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease

Objectives: To explore the relationship between the glymphatic system and various patterns of white matter hyperintensities (WMHs) in the early stages of cerebral small vessel disease (CSVD), as well as their impact on cognitive function. Methods: The report included 84 patients with CSVD and 23 hea...

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Main Authors: Bang Zeng, Peng Zeng, Yayun Xiang, Yuling Peng, Dan Luo, Binglan Li, Ying Chai, Dan Wang, Lisha Nie, Yongmei Li
Format: Article
Language:English
Published: Elsevier 2025-07-01
Series:Brain Research Bulletin
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Online Access:http://www.sciencedirect.com/science/article/pii/S0361923025002035
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author Bang Zeng
Peng Zeng
Yayun Xiang
Yuling Peng
Dan Luo
Binglan Li
Ying Chai
Dan Wang
Lisha Nie
Yongmei Li
author_facet Bang Zeng
Peng Zeng
Yayun Xiang
Yuling Peng
Dan Luo
Binglan Li
Ying Chai
Dan Wang
Lisha Nie
Yongmei Li
author_sort Bang Zeng
collection DOAJ
description Objectives: To explore the relationship between the glymphatic system and various patterns of white matter hyperintensities (WMHs) in the early stages of cerebral small vessel disease (CSVD), as well as their impact on cognitive function. Methods: The report included 84 patients with CSVD and 23 healthy controls (HCs). To comprehensively assess the impact of white matter hyperintensity volume (WMHV) and WMH counts, we introduced the mean WMHV (WMHV/count) as a new biomarker. Using a threshold of 0.1 for mean WMHV, we categorized participants into two groups to compare intergroup differences. The metrics of the glymphatic system included the index of diffusivity along the perivascular space (Analysis aLong the Perivascular Space [ALPS] index) and the fractional volume of free water (FW). Finally, we analyzed the correlations between imaging indicators and cognitive scales using linear regression models. Results: Compared to HC and Group 1 (mean WMHV ≤ 0.1), Group 2 (mean WMHV > 0.1) exhibited a lower ALPS index and higher fractional volume of FW across various brain regions, including the whole brain (FW-ALL), white matter (FW-WM), basal ganglia (FW-BG), and hippocampus (FW-Hipp). In a correlation analysis, the mean WMHV showed significant correlations with FW-ALL, FW-WM, and FW-BG. Meanwhile, WMHV was only correlated with FW-BG. Furthermore, both FW-BG and the ALPS index were associated with Digit Symbol Substitution Test scores. Conclusions: Mean WMHV can reflect the confluence and expansion of WMH and is closely associated with glymphatic system disfunction.
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spelling doaj-art-eac04b8db125433287730265513fab7f2025-08-20T03:25:47ZengElsevierBrain Research Bulletin1873-27472025-07-0122711139110.1016/j.brainresbull.2025.111391Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel diseaseBang Zeng0Peng Zeng1Yayun Xiang2Yuling Peng3Dan Luo4Binglan Li5Ying Chai6Dan Wang7Lisha Nie8Yongmei Li9Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, China; Department of Radiology, People's Hospital of Shapingba District, 44# Xiaolongkan New Street, Chongqing 400010, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, China; Department of Radiology, People's Hospital of Shapingba District, 44# Xiaolongkan New Street, Chongqing 400010, ChinaDepartment of Radiology, Mianyang Central Hospital, 12# Changjia Lane, Mianyang 621000, China; GE Healthcare, MR Research China, Beijing 100076, ChinaDepartment of Radiology, The First Affiliated Hospital of Chongqing Medical University, 1# Youyi Road, Yuan Jiagang, Chongqing 400010, China; Corresponding author.Objectives: To explore the relationship between the glymphatic system and various patterns of white matter hyperintensities (WMHs) in the early stages of cerebral small vessel disease (CSVD), as well as their impact on cognitive function. Methods: The report included 84 patients with CSVD and 23 healthy controls (HCs). To comprehensively assess the impact of white matter hyperintensity volume (WMHV) and WMH counts, we introduced the mean WMHV (WMHV/count) as a new biomarker. Using a threshold of 0.1 for mean WMHV, we categorized participants into two groups to compare intergroup differences. The metrics of the glymphatic system included the index of diffusivity along the perivascular space (Analysis aLong the Perivascular Space [ALPS] index) and the fractional volume of free water (FW). Finally, we analyzed the correlations between imaging indicators and cognitive scales using linear regression models. Results: Compared to HC and Group 1 (mean WMHV ≤ 0.1), Group 2 (mean WMHV > 0.1) exhibited a lower ALPS index and higher fractional volume of FW across various brain regions, including the whole brain (FW-ALL), white matter (FW-WM), basal ganglia (FW-BG), and hippocampus (FW-Hipp). In a correlation analysis, the mean WMHV showed significant correlations with FW-ALL, FW-WM, and FW-BG. Meanwhile, WMHV was only correlated with FW-BG. Furthermore, both FW-BG and the ALPS index were associated with Digit Symbol Substitution Test scores. Conclusions: Mean WMHV can reflect the confluence and expansion of WMH and is closely associated with glymphatic system disfunction.http://www.sciencedirect.com/science/article/pii/S0361923025002035Cerebral small vessel diseaseWhite matter hyperintensitiesGlymphatic system
spellingShingle Bang Zeng
Peng Zeng
Yayun Xiang
Yuling Peng
Dan Luo
Binglan Li
Ying Chai
Dan Wang
Lisha Nie
Yongmei Li
Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
Brain Research Bulletin
Cerebral small vessel disease
White matter hyperintensities
Glymphatic system
title Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
title_full Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
title_fullStr Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
title_full_unstemmed Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
title_short Expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
title_sort expansion of white matter hyperintensities is associated with the glymphatic system dysfunction in cerebral small vessel disease
topic Cerebral small vessel disease
White matter hyperintensities
Glymphatic system
url http://www.sciencedirect.com/science/article/pii/S0361923025002035
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