Favorable cardiovascular health, connectome integrity, and ADRD clinical outcomes and pathologic underpinnings in a diverse cohort.

项目摘要/摘要 随着美国阿尔茨海默病和相关痴呆症(ADRD)年龄别发病率的下降， 在一定程度上，由于心血管健康的改善，我们必须研究如何有利于 心血管健康促进大脑成功老化。良好的心血管健康状况使用 美国心脏协会的《简单生活7》(LS7)被认为是研究成功脑老化的理想指标 鉴于它在保护和促进晚年认知和运动功能方面的作用。存在的有限数据 对LS7和大脑健康的关注集中在孤立性灰质萎缩或白质异常，即白色 物质高强度(WMH)与脑梗塞；到目前为止，还没有研究采用多模式评估 大脑健康与心血管健康有关，或利用连接学领域的进步来 通过基于神经成像数据的全面的神经连接图来研究大脑网络的完整性。 考虑到多个大脑结构变化的贡献是至关重要的，因为大脑变化遭受了 在一个水平上，例如灰质萎缩或以WMH和脑梗塞形式的白质损害，负面 在另一个层面上影响大脑结构，例如，大脑区域之间的连接。 应用以前发布的 方法： 我们将创建多模式结构连接体完整性矩阵，包括细微的大脑变化和 坦率的损害，以填补文献中的空白，并确定LS7如何保护大脑健康和促进 老年非拉丁裔白人、黑人和拉丁裔成年人的认知和运动功能。 为了实现这项研究的总体目标-确定心血管-连接体关系， 促进老年人的大脑健康-我们将结合两年一次的神经成像数据，每年一次的心血管 生活方式和生物学LS7数据，以及对Rush参与者的年度认知和运动测试 记忆和衰老项目，最高可 12 多年的数据收集；其中一部分人也有ADRD 神经病理学数据。450名非拉丁裔黑人和150名非拉丁裔黑人将提供尸检横断面数据 来自另外两项协调的Rush队列研究的拉丁裔参与者。共同努力，这将确保我们的成功 研究连接体完整性的变化和LS7的作用(目标1)，以及连接体的关系 正直与认知和运动能力下降，以及LS7如何变化(目标2)，LS7是否改变了联系 神经病理学和连接体完整性之间的关系(目标3)，以及LS7和LS7的横断面联系 非拉丁裔黑人和拉丁裔成年人的连接体完整性(目标4)。这项研究的交叉性 心血管健康主题，最新的神经成像分析，全面的行为 评估，黄金标准的神经病理学将提供前所未有的丰富信息 并对这一领域产生持续的影响。具体地说，本R01将确定神经病理基础 对晚年脑网络完整性和心血管健康的有利作用，并可能提供完善的MRI 用于对健康状况较差的老年人进行生活方式干预的目标和具体行为结果。

PROJECT SUMMARY/ABSTRACT As age-specific incidence rates of Alzheimer’s disease and related dementias (ADRD) decline in the US, due, in part, to improvements in cardiovascular health, it is imperative that we study how favorable cardiovascular health promotes successful brain aging. Favorable cardiovascular health quantified using The American Heart Association’s Life’s Simple 7 (LS7) is cited as an ideal metric to study successful brain aging given its role in preserving and promoting late-life cognitive and motor functioning. The limited data that exists on LS7 and brain health focuses on isolated grey matter atrophy or white matter abnormalities, i.e., white matter hyperintensities (WMHs) and infarcts; no study, to date, has employed a multi-modal assessment of brain health as related to cardiovascular health, or taken advantage of advances in the field of connectomics to study brain network integrity via comprehensive maps of neural connections based on neuroimaging data. Considering the contribution of multiple brain structural alterations is critical given that brain changes suffered at one level, e.g., grey matter atrophy or white matter damage in the form of WMHs and infarcts, negatively impact brain structure at another level, e.g., connectivity between brain regions. Applying previously published methods, we will create multi-modal structural connectome integrity matrices of subtle brain alterations and frank damage to address gaps in the literature and determine how LS7 preserves brain health and promotes cognitive and motor functioning in older non-Latino White, Black, and Latino adults. To achieve the overall goal of this study – to determine cardiovascular-connectome relationships that promote brain health in older adults – we will combine biennial neuroimaging data, annual cardiovascular lifestyle and biological LS7 data, and annual cognitive and motor testing on 535 participants of the Rush Memory and Aging Project with up to 12 years of data collection; a subset of whom also have ADRD neuropathological data. Ante-mortem, cross-sectional data will be available from 450 non-Latino Black and 150 Latino participants from two other harmonized Rush cohort studies. Together, this will ensure our success investigating change in connectome integrity and the role of LS7 (Aim 1), the relationship of connectome integrity with cognitive and motor decline, and how it varies by LS7 (Aim 2), whether LS7 modifies associations between neuropathology and connectome integrity (Aim 3), and cross-sectional associates of LS7 and connectome integrity within non-Latino Black and Latino adults, separately (Aim 4). This study’s cross-cutting themes of cardiovascular health, state-of-the-art neuroimaging analytics, comprehensive behavioral assessment, and gold-standard neuropathology will provide a wealth of information never before documented and exert a sustained influence on the field. Specifically, this R01 will identify neuropathological underpinnings of late-life brain network integrity and the role of favorable cardiovascular health and may provide refined MRI targets and specific behavioral outcomes for use in lifestyle interventions with less healthy older adults.