Effects of lifetime stress on cognitive aging in the context of HIV-infection: Identifying sources of racial disparities

HIV 感染背景下终生压力对认知衰老的影响：确定种族差异的根源

基本信息

批准号：
10669456
负责人：
APRIL D THAMES
金额：
$ 41.19万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-07-22 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10669456
关键词：
Effects lifetime stress cognitive aging

项目摘要

Project Summary Racial disparities exist in cognitive aging, and it has been established that long-term HIV disease accelerates cognitive aging processes. African Americans (AAs) are a particularly vulnerable group, and our preliminary data indicate that HIV+ AAs demonstrate worse cognitive and brain imaging outcomes than HIV+ EAs even after controlling for confounding factors. We do not know if these disparities persist over time, and the reasons for racial disparities in cognitive outcomes remains unclear. It is well-known that lifetime exposure to stress, which is associated with HIV-infection and AA race, influences cognitive outcomes. Thus, we hypothesize that lifetime stress is a mechanism that places HIV+ AAs at risk for poor cognitive outcomes. Peripheral inflammation has been linked to cognitive impairment in several studies, and is increased in association with HIV, AA race, and lifetime stress. Prospective studies are needed to determine if HIV, lifetime stress exposure and AA race results in premature cognitive aging via increased inflammation. The present study will address this gap in knowledge by examining rates of change in cognitive function and cortical and subcortical brain structures in a cohort of 250 older adults (50+) with and without HIV infection stratified by ethnicity (AA vs. EA). We will also address the gaps in the current stress and disparities literature by using a comprehensive measure of stress and adversity over the lifespan (i.e., Stress and Adversity Inventory [STRAIN]). The STRAIN will allow us to capture stressors that have occurred over an individual’s lifetime as well as new stressors during the course of the study. We will examine how recent stress exposure is associated with changes in inflammation and cognitive/brain outcomes. This study is highly significant, as no study to date has examined racial disparities in risk for cognitive declines in HIV-seropositive individuals. We will use state-of-the art methods for measuring brain changes by following up on a cohort of older (aged 50+) HIV+ and HIV- individuals from a previous NIH supported study. Structural neuroimaging will be used to examine longitudinal changes in morphometry and regional connectivity. The primary aim of this study is to evaluate the prospective change in brain/cognitive function in HIV+ and HIV- adults stratified by AA and EA race. Our secondary aim is to determine how lifetime stress differs as a function of HIV status and race. Our third aim will examine how life stress is associated with prospective changes in cognition/brain structure. Finally, we will examine associations between recent life stress and changes in inflammation, and how these changes in inflammation influence cognitive/brain outcomes. This project brings together the skills of several research groups at UCLA, and builds upon existing collaborations and resources. To our knowledge, this is the first prospective study to evaluate cognitive aging in a large cohort of HIV+ and HIV- AA and EA older adults. At the end of this study we expect to discern the relative contributions of AA and HIV-specific processes as these unfold via inflammatory processes that increase vulnerability to premature aging.

项目概要认知老化方面存在种族差异，并且已经确定长期艾滋病毒疾病加速认知老化过程非裔美国人 (AA) 是一个特别脆弱的群体，我们的初步数据表明，HIV+ AA 表现出比 HIV+ 更差的认知和脑成像结果即使在控制了混杂因素之后，我们也不知道这些差异是否会随着时间的推移而持续存在，并且众所周知，终生接触导致认知结果存在种族差异的原因尚不清楚。与 HIV 感染和 AA 种族相关的压力会影响认知结果。这种终生压力是一种使 HIV+ AA 面临认知结果不佳风险的机制。多项研究表明，外周炎症与认知障碍有关，并且在以下情况下会增加：需要前瞻性研究来确定艾滋病毒、AA 种族和一生压力之间的关系。压力暴露和 AA 种族会因炎症增加而导致认知过早衰老。研究将通过检查认知功能和皮质和皮质的变化率来解决这一知识差距。 250 名感染或未感染 HIV 的老年人（50 岁以上）的皮质下大脑结构按以下因素分层我们还将通过使用 AA 与 EA 来解决当前压力和差异文献中的差距。一生中压力和逆境的综合衡量标准（即压力和逆境量表 [STRAIN]）。STRAIN 将使我们能够捕捉到一个人一生中发生的压力源：以及研究过程中新的压力源，我们将检查最近的压力暴露情况。与炎症和认知/大脑结果的变化相关，这项研究非常重要，因为没有。迄今为止的研究已经调查了艾滋病毒血清阳性个体认知能力下降风险的种族差异。我们将使用最先进的方法通过跟踪一组老年人来测量大脑变化（50 岁以上）来自 NIH 先前支持的研究的 HIV+ 和 HIV- 个体将接受结构神经影像学检查。用于检查形态测量和区域连通性的纵向变化本研究的主要目的。旨在评估按 AA 分层的 HIV+ 和 HIV- 成人的大脑/认知功能的前瞻性变化 EA 种族。我们的次要目标是确定终生压力如何随艾滋病毒状况和种族的变化而变化。我们的第三个目标将研究生活压力如何与认知/大脑结构的预期变化相关。最后，我们将研究近期生活压力与炎症变化之间的关联，以及这些变化如何炎症的变化会影响认知/大脑结果，该项目汇集了多种技能。据我们所知，这就是加州大学洛杉矶分校的研究小组，并以现有的合作和资源为基础。第一项评估大量 HIV+、HIV-AA 和 EA 老年人认知衰老的前瞻性研究。在本研究结束时，我们希望了解 AA 和 HIV 特异性过程的相对贡献：这些通过炎症过程展开，增加了过早衰老的可能性。