Cerebrovascular Mechanisms of Slow Gait and Falls

慢步态和跌倒的脑血管机制

• 批准号: 9099699
• 负责人: LEWIS LIPSITZ
• 金额: $ 40.49万
• 依托单位: HEBREW REHABILITATION CENTER FOR AGED
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9099699
• 关键词: Accounting; Adverse effects; Aging; Analgesics; Area; Attention; Attenuated; Blood; Blood Flow Velocity; Blood Vessels; Blood flow; Boston; Brain; Brain Injuries; Brain region; Carbon Dioxide; Cerebrovascular Circulation; Cerebrum; Characteristics; Clinical Trials; Cognitive; Cohort Studies; Collaborations; Complex; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Elderly; Equilibrium; Executive Dysfunction; Fall prevention; Functional Magnetic Resonance Imaging; Funding; Future; Gait; Gait speed; Goals; Health; Human; Imaging Techniques; Impairment; Independent Living; Individual; Intervention; Life; MRI Scans; Magnetic Resonance Imaging; Maintenance; Measures; Mediating; Metabolic; Morbidity - disease rate; Motor; Neural Pathways; Outcome; Pain; Participant; Performance; Perfusion; Pharmaceutical Preparations; Pilot Projects; Population; Prevention; Productivity; Program Research Project Grants; Recurrence; Regulation; Resources; Risk; Risk Factors; Role; Site; Stimulus; Testing; Transcranial Doppler Ultrasonography; Walking; White Matter Hyperintensity; acronyms; brain volume; cerebral ischemic injury; cerebrovascular; chronic pain; cognitive task; cohort; falls; functional decline; gray matter; hemodynamics; metropolitan; model development; mortality; neuroimaging; neurovascular; neurovascular coupling; novel; population based; prevent; relating to nervous system; response; study population; white matter; white matter damage

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.

描述（由申请人提供）：该提案利用并扩展了 MOBILIZE 波士顿研究 (MBS)，该研究先前证明了老年人代表性人群中异常脑血流 (CBF) 调节、缓慢步态和跌倒之间的显着关系居住在波士顿大都市区的人们。我们的研究结果得出这样的假设：CBF 调节的改变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期间能够将血流重新分配到健康皮质网络的人可以防止步态减慢和跌倒，尽管存在白质损伤。目前的提案将在对 250 名 MBS 参与者进行的第三次评估中添加严格的经颅多普勒和神经影像（结构、扩散张量和功能 MRI）测量，以确定是否：1）响应认知或运动任务（神经血管耦合）而减少 CBF，与 2 年随访期间步态速度减慢、执行功能障碍、功能衰退和反复跌倒纵向相关； 2) CBF 调节异常，包括 CO2 血管反应性和神经血管耦合，与 MRI 和扩散张量成像 (DTI) 上白质和灰质微观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、功能衰退和两年内反复跌倒有关； 4）大脑在认知或运动任务期间增加流向健康区域的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。该研究的独特之处在于，它关注 CBF 的变化作为跌倒的病理机制，开发了尖端的 MR 成像技术来检测可预测跌倒的脑损伤的早期微观结构标记，并确定了一种补偿机制，可以保护某些人免受跌倒的影响。这种跌倒造成的损害——全部发生在一个具有代表性的大型老年人群中。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，目前可以采取的增加脑血流、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跌倒。