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

脑血管病（SVD）是老年人丧失自理能力的主要原因之一。影响日常生活活动的主要临床表现为血管性认知障碍、残疾和步态障碍以及精神障碍。这些症状背后的机制在很大程度上是未知的，这可能是缺乏有效治疗的原因。大脑区域的断裂已经成为疾病的标志。近年来，关于SVD如何影响大脑连通性，已经提出了几种候选机制。这些机制包括微观结构损伤、组织水肿、铁沉积和（皮质）微梗死。解开这些机制的贡献对于确定主要治疗靶点至关重要。磁共振成像（MRI）采集、后处理和分析技术的最新进展使研究大脑在体内的连接成为可能。连通性评估可以依赖于结构或功能度量。从图论衍生的度量（例如网络效率）可以量化全球和区域的大脑连接。我们开始评估SVD的结构和功能连通性。主要目标是：1)识别和评估脑连接改变的不同机制的贡献；2)评估连接改变对临床症状的影响；3)研究连接、认知障碍、步态障碍和精神症状之间复杂的相互作用和调解。该项目采用了一种独特的方法，包括两个大型前瞻性样本：遗传性模型疾病患者（慕尼黑样本）和基于人群的研究对象（格拉茨样本）。该项目将大大受益于数据传输以及两个参与小组的具体专业知识。方法将共同制定，讨论将在项目期间以定期电话会议和面对面会议的形式继续进行。该项目将为SVD的临床相关过程提供新的机制见解，这将导致新的研究和最终治疗策略的发展。

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.