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

• 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
• 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' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' 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

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/少数民族成年人患阿尔茨海默病和相关痴呆症的风险更高 （ADRD）.此外，少数成年人不仅面临更强烈和更频繁的压力， 他们在日常生活中遇到的情况，但他们也有更少的资源来管理这些情况， 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 响应（即，应激反应），特别是交感神经系统的失调 和下丘脑-垂体-肾上腺皮质（HPA）轴。我们对影响的理解 ADRD风险的应激反应来自动物研究和人类实验， 控制实验室压力源这是一个主要限制，因为实验室压力源不能 捕捉个人在日常生活中面临的压力源的种类、严重程度或持续时间。 因此，仍然需要更严格地评估应激反应性与以下因素的关系： 自然环境中的ADRD风险。我们建议通过增加更多的文献来填补这一关键空白。 个性化和客观的指标的压力和压力反应，以长期的 多种族动脉粥样硬化研究（MESA）。我们将利用现有的 基因表达数据，以计算对慢性炎症的生理反应的分子标志物。 暴露在逆境中我们还将收集对压力经历的重复测量， 负面影响（情绪）和心率，以便开发参与者特定的 情感和自主应激反应。我们的总体目标是利用这些 检查身体对压力经历的反应与 ADRD在自然环境中。我们将利用现有的和正在进行的反复评估， 认知功能以及正在进行的两种血管的神经影像学生物标志物评估 AD病理学检查包括脑血流（CBF）、白色高信号、A β 沉积和灰质体积损失。我们提议的研究将使我们开始 解开应激暴露和应激反应性影响血管的途径 痴呆病理学和/或AD阳性。调查结果将为压力管理干预提供信息 以及旨在预防ADRD和/或减缓其进展的精准医学计划。