Solé-Guardia Gemma, Li Hao, Willemse Luc, Lebenberg Jessica, Jouvent Eric, Tuladhar Anil Man
Department of Neurology, Research Institute for Medical Innovation, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Nijmegen, the Netherlands.
Department of Medical Imaging, Anatomy, Research Institute for Medical Innovation, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behavior, Center for Medical Neuroscience, Preclinical Imaging Center PRIME, Radboud Alzheimer Center, Nijmegen, the Netherlands.
Alzheimers Dement. 2025 Apr;21(4):e70212. doi: 10.1002/alz.70212.
Cerebral small vessel disease (SVD) is recognized as a major vascular contributor to cognitive decline, ultimately leading to dementia and stroke. While the pathogenesis of SVD remains unclear, emerging evidence suggests that waste clearance involving perivascular space (PVS) - also known as the glymphatic system - dysfunction may play a role. Among SVD radiological markers, the increased presence of dilated PVS is recognized as a marker of waste clearance disruption. Recently developed neuroimaging methods have been proposed as indirect measures of brain fluid dynamics, but they currently lack formal validation. Here, we provide a comprehensive overview of the latest neuroimaging advancements for assessing brain fluid dynamics, including waste clearance involving PVS function in SVD. We review the mechanisms by which clearance dysfunction might contribute to SVD. Finally, we argue that robust, multimodal, and longitudinal studies are essential for understanding the waste clearance (involving PVS) function and for establishing a diagnostic gold standard. HIGHLIGHTS: The majority of PVS are not visible on MRI, making it crucial to understand how and why they become dilated. The origin of waste clearance involving PVS disruption in SVD may be multifactorial. The BBB and waste clearance (involving PVS) dysfunction likely affect each other, forming a vicious cycle, promoting further amyloid beta accumulation. Yet their direct association in humans over time remains to be studied. Comparative studies can aid in the standardization of methods for assessing waste clearance involving PVS function.
脑小血管病（SVD）被认为是导致认知功能下降的主要血管因素，最终可导致痴呆和中风。虽然SVD的发病机制尚不清楚，但新出现的证据表明，涉及血管周围间隙（PVS）（也称为类淋巴系统）功能障碍的废物清除可能起了作用。在SVD的影像学标志物中，扩张的PVS增多被认为是废物清除障碍的一个标志物。最近开发的神经影像学方法已被提议作为脑液动力学的间接测量方法，但目前它们缺乏正式验证。在此，我们全面概述了评估脑液动力学的最新神经影像学进展，包括SVD中涉及PVS功能的废物清除。我们回顾了清除功能障碍可能导致SVD的机制。最后，我们认为强有力的、多模态的和纵向的研究对于理解废物清除（涉及PVS）功能以及建立诊断金标准至关重要。要点：大多数PVS在磁共振成像（MRI）上不可见，因此了解它们如何以及为何扩张至关重要。SVD中涉及PVS破坏的废物清除起源可能是多因素的。血脑屏障（BBB）和废物清除（涉及PVS）功能障碍可能相互影响，形成恶性循环，促进淀粉样β蛋白进一步积累。然而，它们在人类中的长期直接关联仍有待研究。比较研究有助于评估涉及PVS功能的废物清除方法的标准化。
