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

• 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
• 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

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.

项目摘要 在认知老化方面存在种族差异，已经确定长期感染艾滋病毒的疾病 加速认知老化过程。非洲裔美国人(AA)是一个特别脆弱的群体，我们 初步数据显示，HIV+AA患者的认知和脑成像结果比HIV+患者差 即使在控制了混杂因素之后，EAS也是如此。我们不知道这些差距是否会随着时间的推移而持续下去 造成认知结果种族差异的原因尚不清楚。众所周知，终生接触 压力与艾滋病毒感染和再生障碍性贫血有关，会影响认知结果。因此，我们 假设终生压力是将HIV+AA置于认知结果不良的风险中的一种机制。 在几项研究中，外周炎症与认知障碍有关，而且在 与艾滋病毒、再生障碍性贫血和终生压力有关。需要进行前瞻性研究来确定艾滋病毒的寿命 应激暴露和AA竞赛通过增加炎症导致认知过早老化。现在 这项研究将通过检查认知功能和大脑皮层的变化率来解决这一知识差距 250名有和没有HIV感染的老年人(50+)的皮质下大脑结构按 种族(AA与EA)。我们还将通过使用 寿命内压力和逆境的综合测量(即压力和逆境清单 [品系])。这种压力将使我们能够捕捉到一个人一生中发生的压力源 以及在研究过程中的新的压力源。我们将研究最近的压力暴露情况 与炎症和认知/大脑结果的变化有关。这项研究非常有意义，因为没有 到目前为止，研究已经检查了HIV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年长的人来测量大脑的变化 (50岁以上)来自NIH以前支持的研究的HIV+和HIV-个体。结构神经成像将是 用于检查形态测量和区域连通性的纵向变化。这项研究的主要目的是 目的是评估按AA和AAA分层的HIV+和HIV成人的大脑/认知功能的前瞻性变化 一场比赛。我们的第二个目标是确定一生的压力是如何作为艾滋病毒状况和种族的函数而不同的。 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联。 最后，我们将检查近期生活压力和炎症变化之间的联系，以及这些变化是如何 炎症的变化会影响认知/大脑结果。这个项目集合了几个人的技能 加州大学洛杉矶分校的研究小组，并建立在现有合作和资源的基础上。据我们所知，这是 第一项评估HIV+和HIV-AA和EA老年人群认知老化的前瞻性研究。 在这项研究结束时，我们希望辨别出再生障碍性贫血和艾滋病毒特异性过程的相对贡献，如 这些都是通过炎症过程展开的，这些过程增加了过早衰老的易感性。

项目成果

Racial differences in health and cognition as a function of HIV among older adults.

• DOI: 10.1080/13854046.2021.1967449
• 发表时间: 2022-03
• 期刊: The Clinical neuropsychologist
• 作者: Thames AD;Nunez R;Slavich GM;Irwin MR;Senturk D
• 通讯作者: Senturk D