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

描述（由申请人提供）：高达50%的85岁以上的成年人存在运动障碍，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。脑脊髓微血管病理与晚年运动障碍的总体目标是验证脑和脊髓微血管病理与晚年运动障碍有关的假设。脑成像研究表明，由白质高强度推断的微血管病理是晚年运动障碍的一个重要因素。我们建议直接研究具体的微血管病变，包括小动脉硬化、显微梗死和脑淀粉样血管病。这些病理不可见通过脑成像，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，必须同时检查大脑和脊髓，因为任何一方或两者的损伤都可能导致运动障碍。事实上，尽管脊髓微血管病变已被记录在案，但其对晚年运动障碍的影响尚未得到研究。此外，尽管大脑微血管病理被认为是运动障碍的可能原因，但缺乏来自大脑运动相关区域和脊髓的具有接近死亡临床数据的同一个体的微血管病理的系统研究。从脑认知区收集的死后指数中收集的令人信服的初步数据表明，即使在没有宏观梗死证据的老年人中，微血管病变也存在于35%以上的大脑中，在脊髓中很常见。此外，更严重的大脑微血管病理与更低水平和更快的运动衰退有关。基于这些数据，我们建议利用记忆与衰老项目（R01AG17911）直接检查运动系统的微血管病理。这项研究将捐赠他们已经收集的临床和死后标本，用于从同一个体的大脑和脊髓中收集微血管病理。确定大脑和脊髓的微血管病理有助于晚年进行性运动障碍，将填补我们科学知识中的重要空白，并对缓解这一日益严重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.