Altered glymphatic function and cerebrovascular reactivity in white matter hyperintensities: Insights into cognitive impairment

IF 3.7 3区医学 Q2 NEUROSCIENCES

Brain Research Bulletin Pub Date : 2025-09-16 DOI:10.1016/j.brainresbull.2025.111552

Kai Li , Yueyan Bian , Yi Xing , Xiuqin Jia

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引用次数: 0

Abstract

Objective

White matter hyperintensities (WMH) are linked to cognitive impairment and an increased risk of cerebrovascular and neurodegenerative disorders. While the glymphatic system plays a key role in WMH pathophysiology, the relationship between glymphatic function and cerebrovascular reactivity (CVR) in WMH remains unclear. This study aimed to investigate glymphatic function and CVR in WMH patients with varying lesion severity and cognitive status and to explore their relationship with cognitive performance.

Methods

A total of 124 participants were categorized into three groups based on Fazekas grade and cognitive function: controls (no/mild WMH), moderate-severe WMH without cognitive impairment, and moderate-severe WMH with cognitive impairment no dementia (WMH-CIND). Glymphatic function was assessed using diffusion tensor imaging-analysis along the perivascular space (DTI-ALPS) and global blood oxygen level-dependent cerebrospinal fluid (gBOLD-CSF) coupling from resting-state functional MRI (rs-fMRI). CVR mapping was derived from rs-fMRI, and cognitive performance was evaluated using a comprehensive battery.

Results

The ALPS-index showed a stepwise decline with increasing WMH severity and cognitive impairment (p < 0.001). WMH-CIND participants exhibited lower gBOLD-CSF coupling compared with controls (p < 0.05). CVR alterations were localized to frontal and occipital regions. Significant associations were observed between glymphatic indices, region-specific CVR, and cognitive performance across multiple domains.

Conclusion

These findings highlight the complex interplay between glymphatic dysfunction, localized CVR impairments, and cognitive decline in WMH. Preserving vascular health and optimizing glymphatic clearance may represent promising approaches for controlling WMH progression and its associated cognitive deficits.

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脑白质高信号改变的淋巴功能和脑血管反应性：对认知障碍的认识。

目的：白质高强度（WMH）与认知障碍和脑血管和神经退行性疾病的风险增加有关。虽然淋巴系统在WMH病理生理中起关键作用，但淋巴功能与脑血管反应性（CVR）之间的关系尚不清楚。本研究旨在探讨不同病变严重程度和认知状态的WMH患者的淋巴功能和CVR，并探讨其与认知表现的关系。方法：根据Fazekas评分和认知功能将132名参与者分为3组：对照组（无/轻度WMH）、无认知功能障碍的中重度WMH和认知功能障碍无痴呆的中重度WMH （WMH- cind）。通过静息状态功能MRI （rs-fMRI）沿血管周围空间扩散张量成像分析（DTI-ALPS）和全球血氧水平依赖性脑脊液（gBOLD-CSF）耦合来评估淋巴功能。CVR映射来自rs-fMRI，并使用综合电池评估认知表现。结果：随着WMH严重程度和认知功能障碍的增加，alps指数呈逐步下降趋势。结论：这些发现突出了淋巴功能障碍、局限性CVR障碍和WMH认知功能下降之间复杂的相互作用。保持血管健康和优化淋巴清除可能是控制WMH进展及其相关认知缺陷的有希望的方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Brain Research Bulletin 医学-神经科学

CiteScore

6.90

自引率

2.60%

发文量

253

审稿时长

67 days

期刊介绍： The Brain Research Bulletin (BRB) aims to publish novel work that advances our knowledge of molecular and cellular mechanisms that underlie neural network properties associated with behavior, cognition and other brain functions during neurodevelopment and in the adult. Although clinical research is out of the Journal''s scope, the BRB also aims to publish translation research that provides insight into biological mechanisms and processes associated with neurodegeneration mechanisms, neurological diseases and neuropsychiatric disorders. The Journal is especially interested in research using novel methodologies, such as optogenetics, multielectrode array recordings and life imaging in wild-type and genetically-modified animal models, with the goal to advance our understanding of how neurons, glia and networks function in vivo.