Effects of lifecourse traumatic stress on late-life cognitive decline, dementia, and neuroimaging biomarkers

生命历程创伤应激对晚年认知衰退、痴呆和神经影像生物标志物的影响

• 批准号: 10525615
• 负责人: Eleanor Louise Hayes-Larson
• 金额: $ 12.06万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-04 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10525615
• 关键词: Address; Adult; Affect; African American population; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer’s disease biomarker; Award; Biological Markers; Biometry; Black American; Brain; Characteristics; Child; Clinical; Cognition; Cognitive; Cognitive aging; Complement; Data; Data Pooling; Data Set; Dementia; Education; Elderly; Epidemiology; Ethnic Origin; Etiology; Exposure to; Foundations; Gender; Health; Health and Retirement Study; Heterogeneity; Image; Impaired cognition; Individual; Intervention; Knowledge; Life; Life Experience; Machine Learning; Measures; Mentorship; Methods; Modeling; Neurocognitive; Neurological outcome; Outcome; Pathology; Pathway interactions; Physical activity; Population Heterogeneity; Psychopathology; Psychosocial Factor; Public Health; Race; Research; Research Priority; Research Training; Science; Security; Social Network; Social support; Societal Factors; Statistical Methods; Stress; Stress Tests; Subgroup; Symptoms; Training; Trauma; Woman; Work; aging brain; brain health; career; childhood adversity; cohort; dementia risk; experience; healthy aging; high risk population; improved; middle age; neuroimaging; neuroimaging marker; pediatric trauma; prevent; psychosocial; resilience; sex; skills; social; sociodemographic group; trauma exposure; traumatic event; traumatic stress; treatment effect

Project Summary/Abstract Up to half of Alzheimer’s disease and Alzheimer’s disease-related dementias (AD/ADRD) cases are due to potentially modifiable exposures, including psychosocial factors. Exposure to traumatic events over the lifecourse is pervasive, particularly in groups that experience disproportionately high burden of AD/ADRD. Stress sensitization models suggest that trauma exposure, especially in early life, can result in brain changes and increase vulnerability to psychopathology. However, stress sensitization models have not been extended to late- life neurological outcomes and very little research exists on effects of lifecourse traumatic stress exposure on AD/ADRD risk. The scientific objective of this research plan is to understand effects of traumatic stress on cognition and neuroimaging in late life and to identify factors that modify these effects, including late-life contributors to resilience. Using state-of-the art statistical methods, the research will: (1) estimate the effect of traumatic stress over the lifecourse on late-life cognitive decline, dementia, and neuroimaging biomarkers of AD/ADRD, (2) identify individual characteristics and early-life factors (e.g. sex/gender, race/ethnicity, education) that modify the impact of lifecourse traumatic stress on late-life cognitive decline and dementia, (3) test the stress sensitization model to determine if childhood trauma and adversity modifies the effect of adulthood traumatic stress on late-life cognitive decline and dementia, and (4) identify late-life resilience factors (e.g. social support/integration, financial security, physical activity) that mitigate the impact of lifecourse traumatic stress on late-life cognitive decline and dementia. The proposed data work uses data from the US nationally-representative Health and Retirement Study (HRS) and pooled data from two newly available, harmonized, and diverse cohorts with robust neurocognitive assessments (Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE] and Study of Healthy Aging in African Americans [STAR]). The research addresses the NIA strategic research directions related to understanding effects of personal, interpersonal, and societal factors on aging and disparities in aging. Understanding the impact of lifecourse traumatic stress, including effect modifiers and late- life resilience factors, will improve understanding of determinants of AD/ADRD and inform actionable strategies to prevent AD/ADRD and reduce AD/ADRD disparities. This research plan is complemented by a training plan that builds on the applicant’s background in epidemiology and biostatistics and includes new training to (1) gain strong foundational knowledge in the science and methods of brain and cognitive aging research; (2) develop expertise in the study of trauma and traumatic stress and their impact on brain health, and (3) gain skills in machine learning approaches for causal inference and identifying heterogeneous treatment effects. The combined research and training plans will prepare the applicant for a successful independent research career focused on understanding trauma and other psychosocial determinants of AD/ADRD in diverse populations.

项目摘要/摘要 多达一半的阿尔茨海默氏病和阿尔茨海默氏病有关的痴呆症（AD/ADRD）病例是由于 潜在的可修改暴露，包括社会心理因素。暴露于创伤事件 生命力普遍存在，尤其是在AD/ADRD负担不成比例的群体中。压力 致敏模型表明，创伤暴露，尤其是在早期生命中，会导致大脑变化，并且 增加对心理病理学的脆弱性。但是，压力敏感性模型尚未扩展到晚期 生命神经系统结局和对生命力创伤压力暴露对影响的影响的研究很少 广告/ADRD风险。该研究计划的科学目标是了解创伤性压力对 后期生活的认知和神经影像学，并确定改变这些影响的因素，包括晚期 弹性的贡献者。使用最先进的统计方法，研究将：（1）估计 生命的创伤性压力对晚期认知下降，痴呆和神经影像学的生物标志物的创伤性压力 AD/ADRD，（2）确定个人特征和早期生活因素（例如性别/性别，种族/种族，教育） 这改变了生命性创伤性压力对晚年认知能力下降和痴呆的影响，（3）测试压力 敏化模型以确定儿童创伤和广告是否会改变成年创伤的影响 对晚期认知衰落和痴呆症的压力，以及（4）确定后期的韧性因素（例如社会 支持/整合，财务安全，体育活动）减轻生命性创伤性压力对 晚年认知能力下降和痴呆症。拟议的数据工作使用美国全国代表性的数据 健康与退休研究（HRS），并从两个新近可用的和统一的同类产品中汇总了数据 通过强大的神经认知评估（Kaiser健康衰老和多样化的生活经验[Khandle]和 非裔美国人健康衰老的研究[Star]）。该研究涉及NIA战略研究 与理解个人，人际和社会因素对老龄化和社会因素的影响有关的方向 衰老的差异。了解生命力创伤性压力的影响，包括效应修饰剂和晚期 - 生命的弹性因素，将提高对AD/ADRD决定者的理解，并为可行的策略提供信息 防止AD/ADRD并减少AD/ADRD差异。该研究计划由培训计划完成 这是基于申请人的流行病学和生物统计学背景，包括（1）增益的新培训 大脑和认知衰老研究的科学和方法的强大基础知识； （2）发展 研究创伤和创伤性压力及其对大脑健康的影响的专业知识，以及（3）获得技能 机器学习方法的因果推理和识别异质治疗效果。 联合研究和培训计划将使申请人为成功的独立研究职业做好准备 专注于了解潜水员种群中AD/ADRD的创伤和其他社会心理决定者。