Structural and functional connectivity in cerebral small vessel disease: Mechanistic insights from inherited and sporadic cases

脑部小血管疾病(SVD)是导致老年人丧失独立性的主要原因。影响日常生活能力的主要临床表现为血管认知障碍、残疾和步态障碍以及精神障碍。这些症状背后的机制很大程度上是未知的，这可能解释了为什么缺乏有效的治疗方法。大脑区域的分离已经成为疾病的标志。近年来，关于SVD可能如何影响大脑连通性，人们提出了几种候选机制。这些机制包括微结构损伤、组织水肿、铁沉积和(皮质)微梗塞。弄清这些机制的作用对于确定主要的治疗靶点是至关重要的。磁共振图像(MRI)采集、后处理和分析技术的最新进展使在体内研究脑连接成为可能。连通性评估可以依靠结构性或功能性措施。源自图论的指标(例如网络效率)可以量化全球和区域大脑的连通性。我们开始评估SVD中的结构和功能连通性。主要目标是：i)确定和评估不同机制对大脑连通性改变的贡献，ii)评估连通性改变对临床症状的影响，以及iii)研究连通性、认知障碍、步态障碍和精神症状之间的复杂相互作用和调节。该项目使用了一种独特的方法，包括两个大的预期样本：遗传性模型疾病患者(慕尼黑样本)和基于人群的研究对象(Graz样本)。该项目将从数据传输以及两个参与小组的具体专门知识中受益匪浅。将共同开发方法，并将在项目持续时间内以定期电话会议和面对面会议的形式继续讨论。该项目将提供对SVD临床相关过程的新的机械性见解，这将导致新研究的发展和最终的治疗策略。

Cerebral small vessel disease (SVD) is a major cause for the loss of independence in the elderly. The main clinical manifestations impacting on activities of daily living are vascular cognitive impairment, disability & gait impairment as well as psychiatric disorders. The mechanisms underlying these symptoms are largely unknown, which might explain the lack of efficient therapies.Disconnection of brain regions has emerged as a disease hallmark. In recent years several candidate mechanisms have been postulated for how SVD might impact on brain connectivity. These mechanisms include microstructural damage, tissue edema, iron deposition and (cortical) microinfarcts. Disentangling the contribution of these mechanisms is essential for the identification of the prime therapeutic target.Recent advances in magnetic resonance image (MRI) acquisition, post-processing and analysis techniques enable to study brain connectivity in vivo. Connectivity assessment can rely on structural or functional measures. Metrics derived from graph theory (e.g. network efficiency) allow quantifying global and regional brain connectivity.We set out to evaluate structural and functional connectivity in SVD. The main objectives are i) to identify and assess the contribution of different mechanisms towards altered brain connectivity, ii) to assess the impact of altered connectivity on clinical symptoms, and iii) to study complex interactions and mediation among connectivity, cognitive impairment, gait impairment and psychiatric symptoms.The project uses a unique approach comprising two large, prospective samples: Patients with an inherited model disease (Munich sample) and subjects from a population-based study (Graz sample). The project will greatly benefit from the data transfer as well as the specific expertise of the two participating groups. Methods will be jointly developed and discussions will be continued over the project duration in the form of regular teleconferences and face-to-face meetings.This project will provide new mechanistic insight into clinically relevant processes of SVD, which will lead to the development of new research and ultimately treatment strategies.