Lifespan Vascular Biology on White Matter

项目总结/摘要 血管生物学和白色物质可能是隐藏早期风险机制的一些关键结合点， 血管对认知障碍和阿尔茨海默病的影响。该过程可以开始为 早在青春期和青年期，并贯穿我们的一生。而心血管疾病对白色 我们对生命历程和相关机制的理解 不太清楚。我们的努力旨在确定最早的可能的血管生物标志物和异常的风险因素。 白色物质的变化对应认知能力的下降。脑血管研究的典型重点是 难以逆转的结构成像变化。我们假设白色物质寿命的变化 通过将标准结构成像技术与最先进的技术相结合， 连接体时代的多模式成像。目的是揭示新的血管-白色物质机制， 生物标志物，在不可逆的结构变化发生之前提供早期预警。该提案建立 将Amish Connectome项目的生产力作为基线数据，并利用 脑成像和心血管医学之间的联系。旧秩序阿米什人/门诺派人口 具有更一致的遗传特征，农村生活方式和低酒精和烟草使用，大大减少了 不可控的变异性，从而提供了一个特别有利的平台来研究血管 白色物质的机制。大脑白色物质也将在预测白色的背景下进行研究。 对阿尔茨海默病的易感性。异常血管-白色物质耦合时的跟踪 发生的时间可以提供更有效预防的时间和模式的见解。这项建议是 响应新的NIH Inclusion Across the Lifespan政策。如果成功，拟议的研究应 强烈支持国家阿尔茨海默病项目法案中强调的预防目标，该法案支持 增加公共研究，以预防AD的发病并在2025年前开发有效的治疗方法。预防 通过对连接早期血管的通路进行更细致的了解， 不可逆的白色物质变化。因此，我们建议使用尖端的白色物质成像 这是潜在机制的信息，结合标准但最先进的血管 评估，以研究整个生命周期中血管和白色物质变化之间的相互作用。

Project Summary / Abstract Vascular biology and white matter may be some of the key junctures that harbor early risk mechanisms that precipitate vascular contributions to cognitive impairment and Alzheimer's disease. This process may start as early as adolescence and young adulthood, and through our lifespan. While cardiovascular impacts on white matter health are well-established, our understanding of the lifetime course and the associated mechanisms are less clear. Our efforts aim to identify the earliest possible vascular biomarkers and risk factors for abnormal white matter changes for the corresponding cognitive declines. Cardiovascular-brain studies typical focus on structural imaging changes that are difficult to reverse. We hypothesize that white matter lifespan changes can be more sensitively tracked by combining standard structural imaging techniques with state-of-the-art connectome era multimodal imaging. The goal is to uncover novel vascular - white matter mechanisms and biomarkers that provide early warnings before the irreversible structural changes occur. The proposal builds upon the productivity of the Amish Connectome Project as baseline data, and leverages the collaboration between our brain imaging and cardiovascular medicine groups. The Old Order Amish/Mennonite population has a more uniform genetic profile, rural lifestyle and low alcohol and tobacco use that greatly reduce uncontrollable variability, thus providing a particularly advantageous platform to study the vascular mechanisms on white matter. Cerebral white matter will also be studied in the context of predicting white matter vulnerability to Alzheimer's disease. Tracking when the aberrant vascular – white matter coupling occurs may provide insights into the timing and mode for more effective prevention. This proposal is responsive to the new NIH Inclusion Across the Lifespan policy. If successful, the proposed study should strongly support the prevention goal highlighted in the National Alzheimer's Project Act, which supports increased public research to prevent the onset of and develop effective treatments for AD by 2025. Prevention programs can be benefited by more nuanced understanding of the pathways connecting early vascular changes to irreversible white matter changes. Therefore, we propose to use cutting-edge white matter imaging that is informative of the underlying mechanisms, combined with standard but state-of-the-art vascular assessments, to study the interaction between vascular and white matter changes across lifespan.