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

描述(由申请人提供)：到85岁时，多达50%的成年人存在运动障碍，并与不利的健康后果有关。了解其神经病理学对于努力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检验大脑和脊髓中的微血管病理有助于晚年运动障碍的假说。脑成像研究表明，脑白质高信号所推断的微血管病变是晚年运动障碍的重要因素。我们建议直接研究特定的微血管病变，包括动脉硬化、微小梗塞和脑淀粉样血管病变。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，为了了解晚年的运动障碍，必须同时检查大脑和脊髓，因为其中之一或两者的损伤都会导致运动障碍。事实上，尽管脊髓中的微血管病理已经被记录在案，但它对老年运动障碍的贡献还没有被研究过。此外，虽然脑中的微血管病理被认为是运动障碍的可能原因，但缺乏对具有濒临死亡的临床数据的同一个体的大脑和脊髓运动相关区域的微血管病理的系统研究。从认知脑区收集的尸检指数中令人信服的初步数据显示，即使在没有宏观脑梗塞证据的老年人中，超过35%的大脑中也存在微血管病变，在脊髓中也很常见。此外，大脑中更严重的微血管病变与更低的水平和更快的运动下降有关。在这些数据的基础上，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。这项研究将捐赠他们已经收集的临床和尸检样本，用于拟议从相同个体的大脑和脊髓收集微血管病理。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中的重要空白，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.