Brain pathologies, reserve and cognition in aging and dementia

项目摘要 阿尔茨海默病和相关痴呆症(ADRD)是认知和功能衰退的已知原因，但 一些人对这些疾病的抵抗力更强，并继续正常运作，尽管与 大脑会发生变化。认知储备被引用来解释比预期更好的认知，基于 疾病的存在和严重程度。有证据表明，可改变的生活方式因素可能会建立认知储备； 阐明这些关联对公共卫生政策和干预措施具有重大的实际意义 建立储备，从而减少ADRD的影响，促进健康老龄化。这件事的首要目标是 项目是从一个假设性的、通常是后即席的认知储备结构过渡到一个具体的 理解促进复原力的变量及其预防机制 认知和功能衰退。在此次竞争更新中，我们将使用新的成像方法、 史无前例的多种族/民族样本，并前瞻性地收集了中年数据；每个组成部分 与以前的研究相比，构成了一个重大的创新。目标1将描绘认知基础的大脑资源 和日常功能。我们将使用基于发现的神经成像技术来更好地理解 皮质神经退行性变、血管性脑损伤和淀粉样蛋白沉积对认知和 功能结果。我们将利用四个纵向队列(N=&gt；700)进行协调成像， 四个主要种族/民族(拉丁裔、非拉丁裔亚裔、非拉丁裔)的认知和功能数据 黑人和非拉丁裔白人)来检查种族/民族在大脑中的相似和差异 认知和功能的潜在机制。在目标1中开发的模型也将用于增强 认知储备在计入大脑后作为剩余认知运作的精确度 改变。我们还将我们的认知储备方法扩展到功能储备的可操作性。损失 独立是老年人的主要担忧，更好地了解减少残疾的因素是 危急时刻。目标2将开发认知和功能储备的纵向模型，并研究如何 动态储备影响ADRD的临床结果。目标3将评估生命历程风险和弹性 因素建立或耗尽认知和功能储备，以及这些关系是否因 种族/民族群体。这项研究的一个独特的有价值的贡献将是罕见的检查影响的能力 医疗、生活方式和心理社会数据(血管风险、身体/认知活动、个性、 压力/逆境和社会关系)在20世纪60年代至90年代(中年期间)预期收集的数据)此外 到晚年，从而使我们能够回答有关暴露于储备和保护的关键时期的重要问题 它的生命历程决定因素。该项目将利用独特的数据、多学科的专业知识和 测量大脑-行为关系的创新方法潜在的储备，以解决重要问题 关于认知和功能储备如何有助于不同人群的晚年认知健康。

PROJECT ABSTRACT Alzheimer's disease and related dementias (ADRD) are known causes of cognitive and functional decline, but some individuals are more resilient to these diseases and continue to function normally despite associated brain changes. Cognitive reserve has been invoked to explain better cognition than expected based on the presence and severity of disease. There is evidence modifiable lifestyle factors may build cognitive reserve; elucidating these associations has major practical implications for public health policy and interventions to build reserve, thus reducing the impact of ADRD and promoting healthy aging. The overarching goal of this project is to transition from a hypothetical and often post-hoc construct of cognitive reserve to a concrete understanding of the variables that promote resilience and the mechanisms by which they protect against cognitive and functional decline. In this competitive renewal we will use novel imaging approaches, an unprecedented multi-racial/ethnic sample, and prospectively collected midlife data; each of these components constitutes a major innovation over previous studies. Aim 1 will delineate brain resources underlying cognition and everyday function. We will employ discovery-based neuroimaging techniques to better understand the contributions of cortical neurodegeneration, vascular brain injury, and amyloid deposition to cognitive and functional outcomes. We will leverage four longitudinal cohorts (N = >700) with harmonized imaging, cognitive and functional data among four major racial/ethnic groups (Latinos, non-Latino Asians, non-Latino Blacks, and non-Latino Whites) to examine racial/ethnic group similarities and differences in brain mechanisms underlying cognition and function. Models developed in Aim 1 will also serve to enhance the precision by which we can operationalize cognitive reserve as residual cognition after accounting for brain changes. We also extend our approach for cognitive reserve to operationalize functional reserve. Loss of independence is a major concern for older adults and better understanding factors that reduce disability is critical. Aim 2 will develop longitudinal models of cognitive and functional reserve and investigate how dynamic reserve impacts ADRD clinical outcomes. Aim 3 will evaluate how life course risk and resilience factors build or deplete cognitive and functional reserve and whether these relationships vary across racial/ethnic groups. A uniquely valuable contribution of this study will be the rare ability to examine impacts of medical, lifestyle, and psychosocial data (vascular risks, physical/cognitive activity, personality, stress/adversity and social connection) prospectively collected in the 1960s-1990s (during midlife) in addition to late life, thereby allowing us to answer important questions about critical periods of exposure for reserve and its life course determinants. This project will leverage unique data, multidisciplinary expertise, and an innovative approach for measuring brain-behavior relations underlying reserve to address important questions about how cognitive and functional reserve contribute to late life cognitive health across diverse populations.