Cerebrovascular Mechanisms of Slow Gait and Falls

慢步态和跌倒的脑血管机制

• 批准号: 8875559
• 负责人: LEWIS LIPSITZ
• 金额: $ 39.27万
• 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 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8875559
• 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; Coupling; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Early Diagnosis; Elderly; Equilibrium; Executive Dysfunction; Fall prevention; Functional Magnetic Resonance Imaging; Funding; Future; Gait; 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; Population Study; Prevention; Productivity; Program Research Project Grants; Recurrence; Regulation; Resources; Risk; Risk Factors; Role; Site; Speed; Stimulus; Testing; Transcranial Doppler Ultrasonography; Walking; White Matter Hyperintensity; acronyms; brain volume; cerebrovascular; chronic pain; cognitive task; cohort; falls; functional decline; gray matter; hemodynamics; metropolitan; model development; mortality; neuroimaging; novel; population based; prevent; relating to nervous system; response; 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动员波士顿研究（MBS），该研究先前证明了脑血流异常（CBF）调节（CBF）调节，步态速度缓慢与居住在波士顿Metropolitan地区的代表性老年人中的跌倒。我们的发现导致了以下假设：CBF调节的改变与大脑中脑室和皮质下白质的微血管损伤有关，这最终导致步态，执行功能障碍和下降。我们还假设，尽管存在白质损害，但在认知或运动任务期间可以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。 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随访超过2年； 2）CBF调节中的异常，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）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放缓，执行功能障碍，功能下降和反复发生的情况有关，在2年的时间内下降了； 4）大脑在认知或运动任务期间增加血液流向健康区域的能力会减轻白色或灰质微观结构损害对功能下降和下降的不利影响。这项研究在关注CBF的改变作为跌倒的一种病理机制方面是独一无二的，开发了尖端的MR成像技术，以检测可以预测跌倒的早期微结构标记，并确定某些人免受这种损害的影响，以预测跌倒的跌倒，这些机制在跌倒对跌倒的影响 - 所有这些都在大型老年人中。我们成功的7年保留和MBS队列的随访以及与波士顿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：这项研究将为早期检测和最终预防老年人跌倒和流动性障碍所必需的新信息提供必要的新信息。如果发现异常的脑血流是跌倒的原因，目前可用的干预措施可以增加脑血流，预防脑血管损伤，增加新的血管或建立新的神经途径可能会阻止未来的跌倒。