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: 10538791
• 负责人: Melissa Lamar
• 金额: $ 70.25万
• 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/10538791
• 关键词: Address; Adult; Affect; Age; Aging; Alzheimer' s disease related dementia; American Heart Association; Anisotropy; 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; Gold; Graph; Health; Health Promotion; Incidence; Infarction; Latino; Life; Life Style; Link; Literature; Magnetic Resonance Imaging; Magnetism; Maps; Memory; Methods; Motor; Outcome; Participant; Pathologic; Population; Population Heterogeneity; Positioning Attribute; Predisposition; Publishing; Race; Relaxation; Role; Semantic memory; Speed; Structure; Suggestion; Testing; Time; White Matter Hyperintensity; advanced disease; aging brain; base; behavioral outcome; brain health; cardiovascular disorder risk; cardiovascular health; cerebrovascular pathology; cohort; connectome; gray matter; improved outcome; lifestyle intervention; multimodal neuroimaging; multimodality; neural circuit; neuroimaging; neuropathology; preservation; relating to nervous system; 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) 的年龄特定发病率下降， 部分由于心血管健康的改善，我们有必要研究如何有利地 心血管健康可促进大脑成功衰老。 美国心脏协会的 Life's Simple 7 (LS7) 被认为是研究成功大脑老化的理想指标 鉴于其在保护和促进晚年认知和运动功能方面的作用，现有的数据有限。 关于 LS7 和大脑健康的重点是孤立的灰质萎缩或白质异常，即白质 物质高信号（WMH）和梗塞；迄今为止，尚无研究采用多模式评估 大脑健康与心血管健康相关，或利用连接组学领域的进步来 通过基于神经影像数据的神经连接综合图来研究大脑网络的完整性。 鉴于大脑发生的变化，考虑多种大脑结构改变的贡献至关重要 在某一层面上，例如灰质萎缩或以 WMH 和梗塞形式出现的白质损伤，会产生负面影响 在另一个层面上影响大脑结构，例如大脑区域之间的连接。 应用之前发布的 方法， 我们将创建微妙的大脑变化的多模式结构连接组完整性矩阵 坦率地损害以解决文献中的空白并确定 LS7 如何保持大脑健康并促进 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。 为了实现本研究的总体目标——确定心血管连接组的关系 促进老年人的大脑健康——我们将结合两年一次的神经影像数据、年度心血管数据 对 535 名 Rush 参与者的生活方式和生物 LS7 数据以及年度认知和运动测试 记忆与衰老项目高达 12 多年的数据收集；其中一部分也患有 ADRD 神经病理学数据将来自 450 名非拉丁裔黑人和 150 名非拉丁裔黑人。 来自另外两项协调 Rush 队列研究的拉丁裔参与者共同努力，将确保我们的成功。 研究连接组完整性的变化和 LS7 的作用（目标 1）、连接组的关系 认知和运动能力下降的完整性，以及 LS7 如何改变它（目标 2），LS7 是否改变关联 神经病理学和连接组完整性之间的关系（目标 3），以及 LS7 和 分别研究非拉丁裔黑人和拉丁裔成年人的连接组完整性（目标 4）。 心血管健康、最先进的神经影像分析、综合行为学等主题 评估和金标准神经病理学将提供前所未有的大量信息 具体而言，该 R01 将确定神经病理学基础。 晚年大脑网络完整性和有利心血管健康的作用，并可能提供精细的 MRI 用于对健康状况不佳的老年人进行生活方式干预的目标和具体行为结果。