Brain and Spinal Cord Microvascular Pathology in Late-Life Motor Impairment

描述（由申请人提供）：运动障碍存在于高达50%的85岁以上的成年人中，并与不良健康结果相关。了解其神经病理学对于应对这一日益增长的公共卫生挑战至关重要。脑和脊髓微血管病理学和晚年运动障碍的总体目标是测试脑和脊髓中的微血管病理学有助于晚年运动障碍的假设。脑成像研究表明，微血管病理，如白色物质高信号推断，是一个重要的因素，在晚年运动障碍。我们建议直接研究特定的微血管病变，包括小动脉硬化，显微镜下梗死和脑淀粉样血管病。这些病理通过脑成像是不可见的，只能使用组织病理学技术直接研究。此外，为了了解老年运动障碍，检查大脑和脊髓是必不可少的，因为任何一个或两者的损伤都可能导致运动缺陷。事实上，尽管脊髓中的微血管病理学已经被记录，但其对晚年运动障碍的贡献尚未被研究。此外，尽管脑中的微血管病理被认为是运动障碍的可能原因，但缺乏对来自具有接近死亡的临床数据的相同个体的脑和脊髓的运动相关区域的微血管病理的系统研究。从认知脑区域收集的尸检指数的令人信服的初步数据显示，即使在没有肉眼可见的梗死证据的老年人中，微血管病变也存在于超过35%的大脑中，并且在脊髓中很常见。此外，大脑中更严重的微血管病变与更低水平和更快的运动衰退相关。基于这些数据，我们建议利用记忆和衰老项目（R01AG17911）直接检查运动系统中的微血管病理。本研究将捐赠他们已经收集的临床和尸检标本，用于从同一个体的大脑和脊髓中收集微血管病理学。确定大脑和脊髓中的微血管病理有助于进行性晚年运动障碍，将填补我们科学知识的重要空白，对于缓解这一日益增长的公共卫生挑战的干预措施至关重要。

DESCRIPTION (provided by applicant): Motor impairment is present in up to 50% of adults by age 85 and associated with adverse health outcomes. Understanding its neuropathology is essential for efforts to meet this growing public health challenge. The overall goal of Brain and Spinal Cord Microvascular Pathology and Late-Life Motor Impairment is to test the hypothesis that microvascular pathology in the brain and spinal cord contributes to late-life motor impairment. Brain imaging studies suggest that microvascular pathology, as inferred by white matter hyperintensities, is an important factor in late-life motor impairment. We propose to directly investigate specific microvascular pathologies including, arteriolosclerosis, microscopic infarcts and cerebral amyloid angiopathy. These pathologies are not visible via brain imaging and can only be directly studied using histopathologic techniques. Furthermore, to understand late-life motor impairment it is essential to examine both the brain and spinal cord, since damage to either or both can cause motor deficits. Indeed, though microvascular pathology in the spinal cord has been documented, its contribution to late-life motor impairment has not been studied. Furthermore, although microvascular pathology in the brain is recognized as a possible cause of motor impairment, systematic studies of microvascular pathology from motor-related regions of the brain and the spinal cord from the same individuals with clinical data proximate to death are lacking. Compelling preliminary data from post-mortem indices collected in the cognitive-brain regions show that even among older adults without evidence of macroscopic infarcts, microvascular pathology is present in more than 35% of brains and common in the spinal cord. Further, more severe microvascular pathology in the brain is associated with a lower level and more rapid motor decline. Building on these data, we propose to directly examine microvascular pathology in the motor system by taking advantage of the Memory and Aging Project (R01AG17911). This study will donate the clinical and post-mortem specimens they have already collected for the proposed collection of microvascular pathology from the brain and spinal cord from the same individuals. Establishing that microvascular pathology in the brain and spinal cord contributes to progressive late-life motor impairment would fill important gaps in our scientific knowledge and is essential for interventions to alleviate this growing public health challenge.