Differential Impact of ACEs and Aging on Brain Health

ACE 和衰老对大脑健康的不同影响

• 批准号: 10205925
• 负责人: Cindy Eileen Tsotsoros
• 金额: $ 6.86万
• 依托单位: OKLAHOMA STATE UNIVERSITY STILLWATER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205925
• 关键词: Address; Adult; Age; Age Factors; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Biological; Blood; Brain; Brain Diseases; Brain-Derived Neurotrophic Factor; Child; Childhood; Cognition; Cognitive; Cognitive deficits; Cohort Studies; Collection; Computers; Data; Dementia; Development; Early Intervention; Education; Elderly; Eligibility Determination; Enrollment; Event; Exposure to; Female; Funding; Future; Goals; Gold; Health; High Prevalence; Household; Impaired cognition; Individual; Injury; Intervention; Investigation; Knowledge; Life; Life Experience; Link; Longevity; Measurement; Measures; Memory; Memory Loss; Mental Depression; Mentors; Methods; Modeling; National Institute of General Medical Sciences; Neurocognition; Neurocognitive; Neurophysiology - biologic function; Neuropsychological Tests; Neuropsychology; Participant; Pathway interactions; Pattern; Performance; Persons; Pilot Projects; Population; Process; Prospective cohort study; Public Health; Questionnaires; Recording of previous events; Research; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Scholarship; Serum; Structure; Testing; Training; Trauma; United States National Institutes of Health; Venipunctures; Visit; Woman; Work; adverse childhood events; aged; base; brain health; cognitive function; cognitive performance; cognitive testing; cohort; comorbidity; dementia risk; deprivation; design; early life adversity; emerging adult; experience; healthy aging; human old age (65+); innovation; middle age; neglect; nervous system disorder; neurocognitive test; neurotrophic factor; novel; performance tests; recruit; relating to nervous system; screening; success

PROJECT SUMMARY/ABSTRACT Aging is the number one risk factor for cognitive decline and Alzheimer’s Disease and Related Dementias (ADRD); however, decline in old age may reflect experiences over the entire lifespan. Prior research shows how early-life experiences, such as education, have an influence on late-life cognitive performance and old- age or ADRD cognitive trajectories. Additional early-life factors that may exacerbate neurocognitive degeneration or ADRD risk include adverse childhood experiences (ACEs). An often unconsidered harm of ACEs is the potential risk it poses to brain development and later-life cognitive impairment. ACEs are defined as traumatic childhood events (e.g., abuse, deprivation or neglect, and household challenges). Findings linking ACE exposure to future brain health and disease is concerning given the high prevalence of ACEs. Brain derived neurotrophic factors (BDNF) are also linked to brain and cognitive health, with evidence that aging and neurological diseases reduce the levels of BDNF. Low levels of BDNF in women have been linked to cognitive impairments, depression, and Alzheimer’s disease; however, direct connections between cognitive function and BDNF have yet to be examined. It is unknown how levels of BDNF are impacted by the process of aging and traumatic experiences or how they relate to cognitive testing. Thus, in order to disentangle the contribution of age and ACEs on brain health, it is essential to determine whether ACE-related patterns of cognitive deficits are detectable on neuropsychological testing and whether they relate to BDNF levels among different age cohorts with and without trauma history. Such data will help us understand the relationship between performance-based vs. biologic indicators of brain function across ages. To begin to fill this knowledge gap, the proposed study will leverage findings from an ongoing study of ACEs and neurotrophins in a middle-aged sample to address the following aims: Aim 1: To characterize/define cognitive performance across the emerging and older adult cohorts stratified by ACEs, and Aim 2: To characterize/define BDNF levels across the two unexplored age cohorts stratified by ACEs. Using an observational cohort design, 100 adults―50 emerging adults and 50 older adults―will be recruited for the proposed study. Independent groups will be matched by exposure to ACEs and other key covariates (e.g., education). Participant’s eligibility will be assessed via an online screening questionnaire (and for older adults, an additional in-lab screening prior to beginning the assessment) where eligibility criteria will be confirmed. Those who are eligible and willing to participate will be invited to enroll in the study. Enrolled participants will then have blood drawn prior to completing a computer based cognitive assessment (Automated Neuropsychological Assessment Metrics and NIH-Toolbox Cognitive Battery). This study is an innovative investigation that will have important public health implications. If funded, this study has the ability to identify novel risk factors (e.g., neurocognitive profiles and/or brain substrates) as intervention targets to protect brain health and to promote healthy aging across the lifespan.

项目摘要/摘要 衰老是认知能力下降和阿尔茨海默氏病和相关痴呆症的第一危险因素 （adrd）;但是，老年的下降可能反映出整个生命周期的经历。先前的研究表明 诸如教育之类的早期生活经历如何影响晚年认知表现和旧 年龄或ADRD认知轨迹。可能加剧神经认知的其他早期生活因素 退化或ADRD风险包括不良的儿童期经历（ACE）。经常不考虑的伤害 ACE是它对大脑发育和后期生活认知障碍构成的潜在风险。 ACE被定义 作为创伤性的童年事件（例如虐待，剥夺或忽视以及家庭挑战）。调查结果链接 鉴于ACE的高流行率，ACE暴露于未来的大脑健康和疾病。脑 衍生的神经营养因素（BDNF）也与大脑和认知健康有关，有证据表明衰老和衰老 神经疾病降低了BDNF的水平。女性的BDNF水平低与认知有关 障碍，抑郁和阿尔茨海默氏病；但是，认知功能之间的直接连接 BDNF尚未检查。尚不清楚BDNF的水平如何受老化过程的影响 和创伤经历或它们与认知测试的关系。为了解开贡献 关于大脑健康的年龄和王牌，必须确定是否与ACE相关的认知缺陷模式 可以在神经心理学测试中检测到它们是否与不同年龄之间的BDNF水平相关 有和没有创伤历史的人群。这样的数据将帮助我们了解 基于绩效的与生物学指标的大脑功能跨年龄段。为了开始填补这一知识差距 拟议的研究将利用正在进行的中年ACE和神经营养蛋白的研究中的发现 解决以下目的的样本：目标1：表征/定义跨整个认知表现 通过ACE分层的新兴和老年人群，目标2：以表征/定义BDNF水平 两个意外的年龄人群通过ACE分层。使用观测队列设计，100个成人-50 新兴的成年人和50名老年人将被招募参加拟议的研究。独立团体将是 通过接触ACE和其他关键协变量（例如教育）匹配。参与者的资格将是 通过在线筛查问卷进行评估（对于老年人，在前筛选 开始评估），其中将确认资格标准。那些有资格并愿意的人 参与将邀请参加研究。然后，入学的参与者将在 完成基于计算机的认知评估（自动化神经心理评估指标和 NIH-Toolbox认知电池）。这项研究是一项创新的投资，将具有重要的公共卫生 含义。如果资助，这项研究具有识别新风险因素的能力（例如，神经认知概况 和/或脑底物）作为保护脑健康和促进整个整个脑衰老的干预靶标 寿命。