Myelin Content and Cognitive Trajectories in Young Adults Living with Virally Suppressed HIV

感染病毒抑制的艾滋病毒的年轻人的髓磷脂含量和认知轨迹

• 批准号: 10759305
• 负责人: Payal Patel
• 金额: $ 65.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10759305
• 关键词: Accounting; Address; Adult; Affect; Age; Age Years; Animals; Attenuated; Biological Markers; Blood; Blood Vessels; Brain; Brain Injuries; Cerebrum; Clinical Trials; Cognition; Cognition Disorders; Cognitive; Cross-Sectional Studies; Data; Demyelinations; Development; Diffusion Magnetic Resonance Imaging; Early intervention trials; Educational Status; Etiology; Exclusion; Executive Dysfunction; HIV; HIV Infections; HIV-associated neurocognitive disorder; Health; Image; Imaging Techniques; Impaired cognition; Impairment; Incidence; Individual; Infection; Knowledge; Liquid substance; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Mediating; Mental Health; Methodology; Multiple Sclerosis; Myelin; Myelin Water Imaging; Nervous System Trauma; Neurobehavioral Manifestations; Neurologic; Opportunistic Infections; Outcome; Participant; Pathologic; Pathology; Perinatal; Persons; Phenotype; Plasma; Population; Prevalence; Publishing; Questionnaires; Recording of previous events; Recovery; Research; Risk; Risk Assessment; Risk Factors; Socioeconomic Status; Standardization; Statistical Models; Time; Trauma; Viral; Work; adverse childhood events; age group; antiretroviral therapy; axon injury; biopsychosocial; biopsychosocial factor; cognitive performance; cognitive testing; cohort; comorbidity; daily functioning; executive function; experience; follow-up; high risk; immune activation; improved; in vivo; inflammatory marker; injured; monocyte; myelination; neuroimaging; novel; pharmacologic; pre-exposure prophylaxis; preservation; prospective; remyelination; sex; social health determinants; social stigma; standardize measure; therapeutic target; white matter; white matter change; white matter injury; young adult

Project Summary/Abstract With the introduction of antiretroviral therapy (ART), the prevalence of severe manifestations of HIV-associated neurocognitive disorders has improved over the past few decades. However, in the context of viral suppression, new pressing questions have emerged regarding the etiology of the persistent cognitive sequalae in PLWH on ART. Up to 40% of individuals living with virally suppressed HIV experience cognitive impairment and the mechanisms underlying neurologic injury in these individuals remain poorly understood. A hallmark finding of HIV associated neurocognitive disorder (HAND), white matter injury, has primarily been evaluated indirectly through non-specific markers of myelination on neuroimaging in PLWH or pathologic markers in animal studies. Our team has developed an MRI sequence, myelin water imaging, to directly measure myelin content, a component of white matter, in vivo. We will apply this novel sequence to longitudinally evaluate if reduced myelination rates occur in young adults living with virally suppressed HIV (YLWH) compared to demographic and antiretroviral therapy risk factor matched, HIV-uninfected controls. Additionally, we will evaluate the independent correlation between changes in myelin content and cognitive trajectories, accounting for social determinants of health, to determine if loss of myelin may contribute to the development of cognitive disorders in YLWH. The premise of this application is based on our preliminary data, which demonstrate decreased global and regional myelin content in young adults living with virally suppressed HIV compared to age and sex matched HIV-uninfected controls and that myelin loss mediates the relationship between immune activation and lower domain specific cognitive scores in young adults living with virally suppressed HIV. We will combine our novel imaging methodology assessing myelin content with established imaging techniques, such as diffusion tensor imaging, longitudinally acquired cognitive data and standardized measures of social determinants of health to determine predictors of the latent cognitive phenotypes within our cohort of virally suppressed YLWH using an unbiased statistical modeling approach, group-based trajectory analyses. The information provided by our proposed study will not only improve our understanding of changes in myelin content in YLWH in relation to cognitive outcomes, but also provide the basis for evaluating myelin water imaging as a biomarker to identify PLWH of all ages at risk for cognitive impairment. This work may provide the preliminary data needed to support early intervention trials of myelin preservation or remyelination therapies to improve cognition in a broader population of PLWH.

项目摘要/摘要 随着抗逆转录病毒疗法（ART）的引入，艾滋病毒相关的严重表现的流行率 在过去的几十年中，神经认知障碍有所改善。但是，在病毒的背景下 抑制作用，关于持续认知序列的病因已经出现了新的紧迫问题 在艺术上。多达40％的病毒抑制艾滋病毒的人经历认知障碍 这些个体的神经系统损伤的基础机制仍然很少理解。一个标志 发现HIV相关的神经认知障碍（手），白质损伤，主要评估了 通过在PLWH或病理标记中的神经影像学上的非特异性标记间接地通过 动物研究。我们的团队已经开发了MRI序列，即髓鞘水成像，以直接测量髓鞘 内容，白质的一个组成部分，体内。我们将应用这个新的序列，以纵向评估是否 与病毒抑制的艾滋病毒（YLWH）相比，髓鞘率降低发生 人口统计学和抗逆转录病毒疗法危险因素与HIV未感染的对照相匹配。此外，我们会的 评估髓磷脂含量和认知轨迹的变化之间的独立相关性，会计 对于健康的社会决定因素，以确定髓磷脂损失是否可能有助于认知的发展 YLWH的疾病。此应用程序的前提是基于我们的初步数据 与之相比 年龄和性别匹配的HIV未感染的对照，髓磷脂损失介导免疫之间的关系 病毒抑制HIV的年轻人的激活和较低的域特异性认知评分。我们将 结合我们的新型成像方法，评估髓磷脂含量与既定成像技术 作为扩散张量成像，纵向获得的认知数据和社会标准化措施 健康的决定因素，以确定我们病毒群体中潜在认知表型的预测因子 使用公正的统计建模方法抑制YLWH，基于组的轨迹分析。这 我们提出的研究提供的信息不仅会改善我们对髓磷脂变化的理解 与认知结果有关的YLWH内容，但也为评估髓水提供了基础 成像是一种生物标志物，以识别所有年龄段的认知障碍风险的PLWH。这项工作可以提供 支持髓磷脂保存或再髓样疗法的早期干预试验所需的初步数据 改善广泛的PLWH人群的认知。