Contributions of stress reactivity to risk of Alzheimer's disease and related dementia's in a community-based cohort

在社区队列中压力反应对阿尔茨海默氏病和相关痴呆症风险的影响

基本信息

批准号：
10676249
负责人：
Kiarri N Kershaw
金额：
$ 156.82万
依托单位：
NORTHWESTERN UNIVERSITY AT CHICAGO
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-30 至 2026-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10676249
关键词：
Abeta synthesis Acute Adult Affective Alzheimer&apos s disease pathology Alzheimer&apos s disease related dementia Alzheimer&apos s disease risk Amyloid beta-Protein Animals Atherosclerosis Attention Biological Markers Blood Pressure Blood Vessels Brain Cerebrovascular Circulation Chronic Cognitive Communities Coupled Data Disparity Electrocardiogram Emotions Episodic memory Exposure to Face Gene Expression Genetic Transcription Glucocorticoids Goals Heart Rate Human Hypothalamic structure Impaired cognition Impairment Incidence Individual Intervention Laboratories Life Link Literature Measurement Measures Minority Monitor Multi-Ethnic Study of Atherosclerosis Nerve Degeneration Participant Pathology Pathway interactions Physiological Pituitary Gland Precision Medicine Initiative Prevalence Psychosocial Factor Recommendation Reporting Research Resources Risk Severities Stress Stressful Event Surveys Sympathetic Nervous System System Telephone Testing Vascular Dementia White Matter Hyperintensity abeta deposition adjudication arterial stiffness biological adaptation to stress cognitive function cognitive testing cohort coping dementia risk design ethnic disparity ethnic minority executive function experience experimental study follow-up gray matter heart rate variability high risk hydrocortisone receptor low socioeconomic status memory process molecular marker multi-ethnic multimodal neuroimaging negative affect neuroimaging marker prevent racial disparity racial minority response social stress management stress reactivity stressor symposium vascular cognitive impairment and dementia

项目摘要

Racial/ethnic minority adults are at higher risk for Alzheimer's disease and related dementias (ADRD). Moreover, minority adults are not only exposed to more intense and frequent stressful situations in their daily lives but they also have fewer resources to manage these situations in healthy ways. Limited resources among these adults may lead to impaired physiologic stress responses (i.e., stress reactivity), specifically dysregulation of the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical (HPA) axis. Our understanding of the impact of stress reactivity on ADRD risk comes from animal studies and experiments in humans using controlled, laboratory stressors. This is a major limitation because laboratory stressors cannot capture the variety, severity, or duration of stressors that individuals face in their daily lives. Thus, there remains a need to more rigorously evaluate relationships of stress reactivity with ADRD risk in natural settings. We propose to fill this critical gap in the literature by adding more personalized and objective indicators of stress and stress reactivity to a longstanding community-based cohort, the Multi-Ethnic Study of Atherosclerosis (MESA). We will use existing gene expression data to calculate a molecular marker of the physiologic response to chronic exposure to adversity. We will also collect repeated measurements of stressful experiences, negative affect (emotions), and heart rate in order to develop participant-specific markers of affective and autonomic stress reactivity, respectively. Our overall goal is to use these measures to examine associations of the body's response to stressful experiences with risk of ADRD in a natural setting. We will leverage existing and ongoing repeated assessments of cognitive function as well as ongoing assessments of neuroimaging biomarkers of both vascular and AD pathology including cerebral blood flow (CBF), white matter hyperintensities, Aβ deposition, and gray matter volume loss. Our proposed study will allow us to begin to disentangle the pathways through which stress exposure and stress reactivity impact vascular dementia pathology and/or AD positivity. Findings will inform stress management interventions and precision medicine initiatives designed to prevent ADRD and/or slow its progression.

种族/族裔少数民族成年人患阿尔茨海默氏病和相关痴呆症的风险更高（ADRD）。此外，少数民族不仅面临更激烈和经常压力他们日常生活中的情况，但他们在管理这些情况的资源较少健康的方式。这些成年人的资源有限可能导致生理压力受损反应（即压力反应性），特别是交感神经系统的失调以及下丘脑 - 垂体 - 肾上腺皮质（HPA）轴。我们对影响的影响 ADRD风险的压力反应性来自动物研究和人类的实验受控的实验室压力源。这是一个主要限制，因为实验室压力不能捕获个人在日常生活中面临的压力的多样性，严重性或持续时间。那仍然需要更严格地评估压力反应性的关系自然环境中的ADRD风险。我们建议通过添加更多对长期有压力和压力反应性的个性化和客观指标基于社区的队列，动脉粥样硬化的多种族研究（MESA）。我们将使用现有的基因表达数据，以计算生理反应的分子标记接触广告。我们还将收集重复的压力经历的测量，负面影响（情绪）和心率，以发展参与者的特定标记情感和自主压力反应。我们的总体目标是使用这些措施检查身体对压力经历的反应与风险在自然环境中。我们将利用现有和正在进行的重复评估认知功能以及对两种血管的神经影像标志物的持续评估和AD病理学，包括脑血流（CBF），白质超强度，Aβ 沉积和灰质体积损失。我们提出的研究将使我们开始解开压力暴露和压力反应性影响血管的途径痴呆症病理学和/或阳性。调查结果将为压力管理干预措施提供信息和精确的医学计划旨在防止ADRD和/或减缓其进展。