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

在不同的队列中具有良好的心血管健康、连接组完整性和 ADRD 临床结果和病理基础。

• 批准号: 10669756
• 负责人: Melissa Lamar
• 金额: $ 69.47万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669756
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s disease related dementia; American Heart Association; Anisotropy; Arterioloscleroses; Atrophic; Autopsy; Behavior assessment; Biological; Black race; Brain; Brain region; Cardiovascular system; Clinical; Cognitive; Cohort Studies; Complex; Data; Data Collection; Disease; Elderly; Ensure; Ethnic Origin; Gait speed; Goals; Graph; Health; Health Promotion; Hemorrhage; Incidence; Infarction; Latino; Life; Life Style; Link; Literature; Magnetic Resonance Imaging; Magnetism; Maps; Memory; Methods; Minority Groups; Motor; Outcome; Participant; Pathologic; Population Heterogeneity; Positioning Attribute; Predisposition; Publishing; Race; Relaxation; Role; Semantic memory; Speed; Structure; Testing; Time; White Matter Hyperintensity; advanced disease; aging brain; behavioral outcome; brain health; cardiovascular disorder risk; cardiovascular health; cerebrovascular pathology; cohort; connectome; gray matter; improved; improved outcome; lifestyle intervention; multimodal neuroimaging; multimodality; neural; neural circuit; neuroimaging; neuropathology; preservation; success; white matter; white matter damage; β-amyloid burden

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.

项目摘要/摘要 随着阿尔茨海默氏病和相关痴呆症（ADRD）的年龄特异性发病率在美国下降， 在某种程度上要改善心血管健康，我们必须研究多么有利 心血管健康促进了成功的大脑衰老。使用 美国心脏协会的生活简单7（LS7）被认为是研究成功脑衰老的理想指标 鉴于其在保存和促进后期认知和运动功能方面的作用。存在有限的数据 在LS7和大脑健康上，重点是孤立的灰质萎缩或白质异常，即白色 物质高强度（WMHS）和Infracts；迄今为止，尚无研究的研究 与心血管健康有关的大脑健康，或利用连接组领域的进步 研究大脑网络完整性通过基于神经影像数据的神经元连接的综合图。 考虑到大脑变化遭受的大脑变化，考虑到多种大脑结构的贡献至关重要 在一个层面上，例如，灰质萎缩或白质损害WMHS和Infacts的形式，负面 影响大脑在另一个级别，例如大脑区域之间的连通性。 应用先前发布的 方法， 我们将创建微妙的大脑改变和 坦率的损害解决文献中的差距，并确定LS7如何保存大脑健康并促进 较老的非拉丁裔白色，黑色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 - 连接的关系 促进老年人的大脑健康 - 我们将结合双年期神经影像学数据，年度心血管 生活方式和生物LS7数据，以及535名参与者的年度认知和运动测试 记忆和老化项目， 12 数据收集年；其中一个子集也有adrd 神经病理学数据。前验尸，横截面数据将提供450个非Latino黑色和150 来自另外两个统一的Rush队列研究的拉丁裔参与者。在一起，这将确保我们的成功 调查连接组完整性的变化和LS7的作用（AIM 1），Connectome的关系 认知和运动下降的完整性，以及它如何随LS7的变化（AIM 2），LS7是否修改关联 在神经病理学和连接组完整性（AIM 3）以及LS7和LS7的横截面关联之间 分别在非拉丁裔黑人和拉丁裔成年人中的连接组完整性（AIM 4）。这项研究的横切 心血管健康，最先进的神经影像学分析，全面行为的主题 评估和金标准神经病理学将提供从未有过记录的大量信息 并对该领域产生持续的影响。具体而言，该R01将识别神经病理学基础 晚期大脑网络完整性和有利的心血管健康的作用，并可能提供精致的MRI 目标和特定的行为结果用于生活方式干预措施，老年人健康。