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

艾滋病毒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: 10207358
• 负责人: APRIL D THAMES
• 金额: --
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-03 至 2021-07-02
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10207358
• 关键词: AIDS/HIV problem; Address; Adult; African American; American; Area; Biological; Brain; Brain imaging; C-reactive protein; CCL2 gene; CD14 gene; Chronic; Chronic stress; Climacteric; Clinical; Cognition; Cognitive; Cognitive aging; Collaborations; Data; Development; Disease; Disease Management; Education; Elderly; Environmental Risk Factor; Equipment and supply inventories; Ethnic Origin; European; Exposure to; HIV; HIV Infections; HIV Seronegativity; HIV-associated neurocognitive disorder; Immunology; Impaired cognition; Individual; Infection; Inflammation; Inflammatory; Interleukin-10; Interleukin-6; Intervention; Knowledge; Life Stress; Link; Literature; Longevity; Measures; Memory; Methods; NIH Office of AIDS Research; National Institute of Mental Health; Neurocognitive; Neurosciences; Outcome; Participant; Perception; Peripheral; Population; Premature aging syndrome; Process; Prospective Studies; Race; Research; Resources; Risk; Sampling; Source; Stereotyping; Stress; Structure; TNF gene; Time; United States National Institutes of Health; Vulnerable Populations; Work; aged; base; brain abnormalities; cognitive function; cohort; executive function; experience; healthspan; high risk; improved; morphometry; neurocognitive disorder; neuroimaging; novel; premature; prospective; psychosocial; racial discrimination; racial disparity; rate of change; response; seropositive; skills; social; socioeconomics; stressor; white matter

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 种族差异存在于认知衰老中，并且已经确定长期艾滋病毒疾病 加速认知衰老过程。非裔美国人（AAS）是一个特别脆弱的群体，我们 初步数据表明，与HIV+相比，HIV+ AAS表现出更差的认知和大脑成像结果 EAS即使控制了混杂因素。我们不知道这些差异是否会随着时间的流逝而持续存在，并且 认知结果中种族差异的原因尚不清楚。众所周知，终身暴露 与HIV感染和AA种族有关的压力会影响认知结果。因此，我们 假设终生应力是一种使HIV+ AAS面临不良认知结果的风险的机制。 在几项研究中，周围炎症与认知障碍有关，并增加 与艾滋病毒，AA种族和终生压力有关。需要前瞻性研究来确定艾滋病毒，寿命是否 压力暴露和AA种族通过增加的炎症导致过早的认知衰老。现在 研究将通过检查认知功能和皮质的变化率以及 由250名老年人（50+）组成的皮层脑结构，有和没有HIV感染。 种族（AA与EA）。我们还将通过使用一个 全面衡量压力和逆境的寿命（即压力和逆境清单 [拉紧]）。这种压力将使我们能够捕获个人一生中发生的压力源 以及在研究过程中的新压力源。我们将研究最近的压力暴露 与炎症和认知/大脑结局的变化有关。这项研究非常重要，因为没有 迄今为止的研究检查了艾滋病毒阳性个体认知下降的风险种族差异。 我们将使用最先进的方法来测量大脑的变化，以跟进一系列较旧的人群 （50岁以上的）HIV+和HIV-来自先前的NIH支持的研究。结构性神经影像学将是 用于检查形态计量学和区域连通性的纵向变化。这项研究的主要目的 是为了评估HIV+和HIV的大脑/认知功能的前瞻性变化 - 由AA分层和 EA比赛。我们的次要目的是确定终身压力与艾滋病毒状况和种族的函数的差异。 我们的第三个目标将研究生命压力与认知/大脑结构的前瞻性变化如何相关。 最后，我们将研究最近的生命压力与炎症变化之间的关联，以及这些如何 炎症的变化会影响认知/大脑结果。这个项目汇集了几个技能 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。据我们所知，这是 在大量的HIV+和HIV-AA和EA老年人中评估认知衰老的第一项前瞻性研究。 在这项研究结束时 这些通过炎症过程展开，从而增加了过早衰老的脆弱性。