Differential Impact of ACEs and Aging on Brain Health

ACE 和衰老对大脑健康的不同影响

基本信息

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
项目类别：
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&apos s Disease Alzheimer&apos s disease related dementia Alzheimer&apos 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

项目摘要

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.

项目概要/摘要衰老是认知能力下降和阿尔茨海默病及相关痴呆症的第一大风险因素 (ADRD)；然而，先前的研究表明，老年的衰退可能反映了整个生命周期的经历。早期生活经历（例如教育）如何影响晚年的认知表现和老年经历年龄或 ADRD 认知轨迹可能会恶化神经认知的其他早期因素。退化或 ADRD 风险包括不良童年经历 (ACE) 的一种经常被忽视的危害。 ACE 是它对大脑发育造成的潜在风险，ACE 被定义为晚年认知障碍。童年创伤事件（例如虐待、剥夺或忽视以及家庭挑战）。鉴于 ACE 的高患病率，ACE 暴露对未来大脑健康和疾病的影响值得关注。衍生性神经营养因子（BDNF）也与大脑和认知健康有关，有证据表明衰老和神经系统疾病会降低女性 BDNF 的水平。女性的 BDNF 水平低与认知能力有关。然而，认知功能障碍、抑郁症和阿尔茨海默病之间存在直接联系。 BDNF 的水平如何受到衰老过程的影响尚不清楚。以及创伤经历或它们与认知测试的关系，以便理清其贡献。年龄和 ACE 对大脑健康的影响，有必要确定 ACE 相关的认知缺陷模式是否存在可以通过神经心理学测试检测到，以及它们是否与不同年龄段的 BDNF 水平相关有和没有创伤史的队列这些数据将帮助我们了解之间的关系。为了填补这一知识空白，基于表现的大脑功能与跨年龄段的生物指标进行了比较。拟议的研究将利用一项正在进行的针对中年人的 ACE 和神经营养素研究的结果样本来实现以下目标：目标 1：描述/定义跨领域的认知表现按 ACE 分层的新兴和老年群体，目标 2：描述/定义整个群体的 BDNF 水平采用观察性队列设计，对 100 名成年人（50 名）进行了按 ACE 分层的两个未探索的年龄组。拟议的研究将招募新兴成年人和 50 名老年人。与 ACE 和其他关键协变量（例如，教育程度）的接触相匹配。通过在线筛查问卷进行评估（对于老年人，在评估之前进行额外的实验室筛查开始评估），将确认那些有资格并愿意的人。参与者将被邀请参加研究。然后，注册的参与者将在研究之前进行抽血。完成基于计算机的认知评估（自动神经心理学评估指标和 NIH-Toolbox 认知电池）。这项研究是一项创新研究，将对公众健康产生重要影响。如果获得资助，这项研究有能力识别新的风险因素（例如神经认知特征）。和/或脑基质）作为干预目标，以保护大脑健康并促进健康老龄化寿命。