Cerebrovascular Mechanisms of Slow Gait and Falls

描述（由申请人提供）：该提案利用并扩展了MOBILIZE Boston研究（MBS），该研究先前证明了在波士顿大都市区老年人的代表性人群中，异常脑血流量（CBF）调节、缓慢步态速度和福尔斯发生之间的显著关系。我们的研究结果导致了这样一种假设，即CBF调节的改变与脑中脑室周围和皮质下白色物质的微血管损伤有关，最终导致步态减慢、执行功能障碍和福尔斯。我们还假设，那些在认知或运动任务中能够将血流重新分配到健康皮层网络的人可以防止步态减慢和福尔斯，尽管存在白色损伤。目前的提案将增加严格的经颅多普勒和神经成像（结构、弥散张量和功能性MRI）测量250名MBS参与者的第三次评估，以确定是否：1）响应认知或运动任务的CBF减少（神经血管耦合），纵向与步态速度减慢，执行功能障碍，功能下降，并在2年以上的随访复发福尔斯; 2）CBF调节的异常，包括CO2血管反应性和神经血管偶联，与MRI和扩散张量成像（DTI）上的白色和灰质微结构完整性的丧失有关; 3）大脑中的这些结构变化与步态减慢、执行功能障碍、功能下降和2年以上的复发性福尔斯有关;以及4）在认知或运动任务期间大脑增加流向健康区域的血流量的能力可以减弱白色或灰质微结构损伤对功能衰退和福尔斯的不利影响。这项研究的独特之处在于，重点关注CBF的改变作为福尔斯的病理机制，开发尖端的MR成像技术来检测可以预测福尔斯的脑损伤的早期微结构标志物，并确定一种补偿机制，保护一些人免受这种损伤对福尔斯的影响-所有这些都是在一个大型的代表性老年队列中进行的。我们对MBS队列的成功7年保留和随访以及与波士顿VA神经影像中心的合作将有助于确保我们实现目标。相关性：这项研究将为早期发现和最终预防老年人福尔斯和行动障碍的脑血管原因提供必要的新信息。如果发现脑血流量异常是福尔斯的原因，那么目前可用的增加脑血流量、预防脑血管损伤、生长新血管或建立新神经通路的干预措施可能会预防未来的福尔斯。

DESCRIPTION (provided by applicant): This proposal leverages and extends the MOBILIZE Boston Study (MBS), which previously demonstrated significant relationships between abnormal cerebral blood flow (CBF) regulation, slow gait speed, and the development of falls in a representative population of elderly people living in the Boston metropolitan area. Our findings have led to the hypothesis that alterations in CBF regulation are associated with microvascular damage to periventricular and subcortical white matter in the brain, which ultimately results in slowing of gait, executive dysfunction, and falls. We also hypothesize that those individuals who can redistribute blood flow to healthy cortical networks during cognitive or motor tasks can prevent slowing of gait and falls, despite the presence of white matter damage. The current proposal will add rigorous transcranial Doppler and neuroimaging (structural, diffusion tensor, and functional MRI) measures to the third assessment of 250 MBS participants to determine whether: 1) reduced CBF in response to a cognitive or motor task (neurovascular coupling), is longitudinally associated with the slowing of gait speed, executive dysfunction, functional decline, and recurrent falls over 2 years of followup; 2) abnormalities in CBF regulation, including CO2 vasoreactivity and neurovascular coupling, are associated with loss of white and gray matter microstructural integrity on MRI and diffusion tensor imaging (DTI); 3) these structural changes in the brain are associated with slowing of gait, executive dysfunction, functional decline, and recurrent falls over 2 years; and 4) the brain's ability to increase blood flow to healthy regions during cognitive or motor tasks can attenuate the adverse effects of white or gray matter microstructural damage on functional decline and falls. The study is unique in focusing on alterations in CBF as a pathological mechanism of falls, developing cutting-edge MR imaging techniques to detect early microstructural markers of brain damage that can predict falls, and identifying a compensatory mechanism that protects some people from the effects of this damage on falls - all in a large representative elderly cohort. Our successful 7-year retentio and followup of the MBS cohort and collaboration with the Boston VA Neuroimaging Center will help assure we achieve our goals. Relevance: This study will provide novel information necessary for the early detection and ultimate prevention of cerebrovascular causes of falls and mobility impairments in elderly people. If abnormal brain blood flow is discovered to be a cause of falls, currently available interventions to increase brain blood flow, prevent cerebrovascular damage, grow new blood vessels, or build new neural pathways may prevent future falls.