Cerebrovascular Mechanisms of Slow Gait and Falls

描述（由申请人提供）：该提案利用并扩展了mobileboston研究（MBS），该研究先前证明了在居住在波士顿大都会地区的具有代表性的老年人中，异常脑血流量（CBF）调节、慢速步态和跌倒发展之间的显著关系。我们的研究结果提出了一种假设，即脑血流调节的改变与脑室周围和皮层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液重新分配到健康皮层网络的人，尽管存在白质损伤，但可以防止步态减慢和跌倒。目前的提案将在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）反应的CBF减少是否与2年随访期间的步态速度减慢、执行功能障碍、功能衰退和复发性跌倒具有纵向相关性；2)脑血流调节异常，包括CO2血管反应性和神经血管耦合，与MRI和弥散张量成像（DTI）显示的白质和灰质微结构完整性丧失有关；3)这些大脑结构变化与2年内步态减慢、执行功能障碍、功能下降和反复跌倒有关；4)大脑在认知或运动任务中增加健康区域血流量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关注CBF的改变作为跌倒的病理机制，开发尖端的MR成像技术来检测可以预测跌倒的早期脑损伤微结构标记，并确定一种补偿机制，保护一些人免受这种损伤对跌倒的影响-所有这些都是在一个具有代表性的老年队列中进行的。我们对MBS队列的7年成功保留和随访以及与波士顿VA神经成像中心的合作将有助于确保我们实现目标。相关性：本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量是导致跌倒的原因，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预防未来的跌倒。

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.