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.

项目总结/摘要 多达一半的阿尔茨海默病和阿尔茨海默病相关痴呆（AD/ADRD）病例是由于 潜在的可改变的暴露，包括心理社会因素。1990年代遭受创伤性事件 在生活过程中普遍存在，特别是在经历AD/ADRD负担不成比例高的群体中。应力 致敏模型表明，创伤暴露，特别是在生命早期，可导致大脑变化， 增加对精神病理学脆弱性。然而，应激致敏模型尚未扩展到晚期- 生活神经系统的结果，很少有研究存在的影响，生活过程中的创伤应激暴露， AD/ADRD风险。这项研究计划的科学目标是了解创伤压力对 认知和神经成像，并确定修改这些影响的因素，包括晚年 对恢复力的贡献。本研究采用最先进的统计方法，将：（1）估计 生命过程中的创伤应激对晚年认知能力下降、痴呆和神经影像学生物标志物的影响 AD/ADRD，（2）确定个体特征和早期因素（例如性别/性别、种族/民族、教育） 修改生命过程创伤应激对晚年认知能力下降和痴呆的影响，（3）测试压力 致敏模型，以确定童年创伤和逆境是否会改变成年创伤的影响， 强调晚年认知能力下降和痴呆，以及（4）确定晚年恢复力因素（例如社会 支持/融入、经济保障、体育活动），以减轻生命过程创伤压力对 老年认知能力下降和痴呆拟议的数据工作使用的数据来自美国全国代表性的 健康与退休研究（HRS）和来自两个新获得的、统一的和不同的队列的汇总数据 通过强大的神经认知评估（Kaiser Healthy Aging and Diverse Life Experiences [KHANDLE]和 非裔美国人健康老龄化研究[星星]）。本研究主要针对NIA战略研究 与理解个人、人际和社会因素对衰老的影响有关的方向， 老龄化的差异。了解生命过程创伤应激的影响，包括效应调节剂和晚期- 生活弹性因素，将提高对AD/ADRD决定因素的理解，并为可采取的战略提供信息 预防AD/ADRD并减少AD/ADRD差异。这个研究计划由一个培训计划补充 这是建立在申请人的流行病学和生物统计学的背景，并包括新的培训，以（1）获得 在大脑和认知衰老研究的科学和方法方面有很强的基础知识;（2）发展 在创伤和创伤应激及其对大脑健康的影响的研究的专业知识，（3）获得技能， 用于因果推理和识别异质性治疗效果的机器学习方法。的 结合研究和培训计划将准备申请人成功的独立研究生涯 重点是了解不同人群中AD/ADRD的创伤和其他心理社会决定因素。