Cerebrovascular Mechanisms of Slow Gait and Falls

描述(由申请人提供)：这项建议利用并扩展了波士顿动员研究(MBS)，该研究先前证明了在波士顿大都市区具有代表性的老年人中，脑血流调节异常、步态速度缓慢和跌倒的发生之间存在显著关系。我们的发现导致了一种假说，即CBF调节的变化与脑室周围和皮质下白质的微血管损伤有关，最终导致步态减慢、执行功能障碍和跌倒。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质网络的人，可以防止步态和跌倒的放缓，尽管存在白质损伤。目前的建议将在对250名MBS参与者的第三次评估中增加严格的经颅多普勒和神经成像(结构、扩散张量和功能MRI)测量，以确定：1)认知或运动任务(神经血管耦合)导致的CBF减少，纵向上与步速减慢、执行功能障碍、功能衰退和2年后反复跌倒有关；2)CBF调节异常，包括二氧化碳血管反应性和神经血管耦合，与MRI和扩散张量成像(DTI)上白色和灰质微结构完整性的丧失有关；3)大脑的这些结构变化与步态减慢、执行功能障碍、功能衰退和两年后反复跌倒有关；4)在认知或运动任务中，大脑增加流向健康区域的血液的能力可以减轻白质或灰质微结构损伤对功能衰退和跌倒的不利影响。这项研究的独特之处在于，专注于将CBF的变化作为跌倒的病理机制，开发尖端的磁共振成像技术来检测可以预测跌倒的早期脑损伤微观结构标志，并确定保护一些人免受跌倒影响的代偿机制-所有这些都是在一个具有代表性的大型老年队列中进行的。我们对MBS队列的成功7年保留和跟踪以及与波士顿退伍军人管理局神经成像中心的合作将有助于确保我们实现我们的目标。相关性：这项研究将为早期发现和最终预防老年人跌倒和行动障碍的脑血管原因提供必要的新信息。如果发现异常的脑血流是跌倒的原因，目前可用的增加脑血流量、防止脑血管损伤、生长新血管或建立新的神经通路的干预措施可能会防止未来跌倒。

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.