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

项目概要/摘要 随着美国阿尔茨海默病和相关痴呆症（ADRD）的年龄特异性发病率下降， 部分由于心血管健康的改善，我们必须研究如何有利 心血管健康促进成功的大脑老化。有利的心血管健康量化使用 美国心脏协会的生活简单7（LS 7）被认为是研究成功大脑衰老的理想指标 鉴于其在保护和促进晚年认知和运动功能方面的作用。现有的有限数据 关于LS 7和脑健康的研究集中在孤立的灰质萎缩或白色物质异常，即，白色 物质高信号（WMH）和梗死;迄今为止，没有研究采用多模式评估 大脑健康与心血管健康有关，或者利用连接组学领域的进展， 通过基于神经成像数据的神经连接的综合地图来研究大脑网络的完整性。 考虑到大脑的变化遭受的多种大脑结构改变的贡献是至关重要的 在一个级别，例如，灰质萎缩或白色损害，表现为WMH和梗死， 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， 我们将创建多模态结构连接体完整性矩阵的微妙的大脑变化， 坦率的损害，以解决文献中的差距，并确定LS 7如何保护大脑健康， 老年非拉丁裔白色、黑人和拉丁裔成年人的认知和运动功能。 为了实现本研究的总体目标-确定心血管-连接体关系， 促进老年人的大脑健康-我们将联合收割机结合两年一次的神经成像数据， 生活方式和生物LS 7数据，以及对535名Rush参与者的年度认知和运动测试 记忆和衰老项目， 12 数据收集年;其中一个子集也患有ADRD 神经病理学数据。将从450名非拉丁裔黑人和150名 拉丁裔参与者来自另外两项统一的Rush队列研究。这将确保我们的成功 研究连接体完整性的变化和LS 7的作用（目的1），连接体的关系 完整性与认知和运动能力下降，以及它如何通过LS 7变化（目标2），LS 7是否修改关联 神经病理学和连接体完整性之间的关系（目标3），以及LS 7和 非拉丁美洲黑人和拉丁美洲成年人的连接体完整性（目标4）。这项研究是跨领域的 心血管健康、最先进的神经影像分析、全面的行为医学、 评估和黄金标准的神经病理学将提供丰富的信息从来没有记录 并对这个领域产生持续的影响。具体而言，该R 01将识别神经病理学基础 晚年大脑网络的完整性和有利心血管健康的作用，并可能提供完善的MRI 目标和具体的行为结果，用于对不太健康的老年人进行生活方式干预。

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.