Cerebrovascular mechanisms of HIV-associated cognitive impairment in China

中国HIV相关认知障碍的脑血管机制

• 批准号: 9344712
• 负责人: Felicia C. Chow
• 金额: $ 16.84万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-07 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9344712
• 关键词: AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Affect; Age; Age-Years; Attention; Brain Injuries; California; Caring; Cerebral small vessel disease; Cerebrovascular Disorders; Cerebrum; China; Chinese People; Clinical Research; Collaborations; Communicable Diseases; Country; Cross-Sectional Studies; Data; Data Collection; Development; Diagnosis; Disease Marker; Disease Progression; Doppler Ultrasound; Fellowship; Foundations; Funding; Future; General Population; Goals; Grant; HIV; HIV Infections; HIV-associated neurocognitive disorder; Health; Hospital Departments; Human Resources; Impaired cognition; Impairment; Incidence; Individual; Injury; Intervention; Knowledge; Link; Longitudinal cohort; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Microvascular Dysfunction; Modality; Neurocognitive Deficit; Neurology; Neuropsychological Tests; Participant; Pathogenesis; Patients; Performance; Physicians; Pilot Projects; Population; Preparation; Prevention strategy; Preventive; Procedures; Protocols documentation; Public Health; Radiology Specialty; Recruitment Activity; Regimen; Reporting; Research; Research Infrastructure; Research Methodology; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; San Francisco; Severities; Severity of illness; Shapes; Site; Standardization; Stroke; Techniques; Therapeutic; Time; Training; Treatment Efficacy; Ultrasonography; United States; Universities; Viral; antiretroviral therapy; cerebrovascular; cognitive function; cost effective; data management; early onset; efficacy testing; endothelial dysfunction; experience; improved; insight; low and middle-income countries; medical schools; neuroimaging; pre-clinical; prevent; programs; quality assurance; tool

PROJECT SUMMARY HIV-associated neurocognitive disorders (HAND) remain prevalent in the current era of combination antiretroviral therapy. Despite the persistence of HAND, the pathogenesis of neurocognitive impairment in HIV is poorly understood. Increasing attention has been paid to the role of cerebrovascular injury in HAND. We hypothesize that impaired cerebral endothelial function in the setting of cerebral small vessel disease is a contributing factor to the development of neurocognitive impairment in HIV-infected individuals. In China, where the number of diagnosed cases of HIV infection is on the rise and the burden of cerebrovascular disease is high, understanding the association between cerebrovascular disease and HAND is particularly relevant. This planning grant brings together researchers from the United States and China to build sustainable capacity to conduct research on HAND in a resource-limited setting in China in order to reach our long-term goal of developing strategies to risk stratify, prevent and treat neurocognitive impairment in HIV. We will leverage an existing collaboration between the University of California, San Francisco Department of Neurology and the Peking Union Medical College Hospital Department of Infectious Diseases, in addition to the research infrastructure of the China AIDS Clinical Trials Group, to implement a pilot study aimed at: (1) estimating the association of HIV infection with transcranial Doppler ultrasound (TCD)-assessed cerebral endothelial function measured by cerebral vasoreactivity and (2) evaluating the correlation between cerebral vasoreactivity and markers of brain injury, including small vessel disease, on neuroimaging in a cross-section of treated, virally suppressed, older HIV-infected individuals and demographically-matched uninfected controls; (3) estimating the association of cerebral vasoreactivity with HAND and cognitive decline in a longitudinal cohort of treated, virally suppressed, older HIV-infected individuals and demographically-matched uninfected controls; and (4) developing human resources and infrastructure to conduct clinical research on HAND in Yunnan, China by training local staff in the performance of TCD and neuropsychological testing and in clinical research methods, developing and refining study procedures for participant recruitment, data collection and data management, and promoting rigorous research practices through use of standardized protocols and quality assurance. The data and experience generated from this pilot study will lay the foundation for a definitive R01-funded longitudinal cohort study investigating cerebrovascular mechanisms of HAND in China with the goal of identifying potential preclinical markers of disease, determining the correlation between cerebral endothelial function and disease severity and progression, and testing the efficacy of interventions that improve cerebral endothelial function on HAND for use in HIV populations in China, the US and worldwide.

项目摘要 HIV相关的神经认知障碍（HAND）在当前的联合时代仍然普遍存在 抗逆转录病毒疗法尽管HAND持续存在，但HIV神经认知障碍的发病机制 是很难理解的。脑血管损伤在HAND中的作用日益受到重视。我们 假设在脑小血管疾病情况下受损的脑内皮功能是 HIV感染者神经认知功能障碍的发展的促成因素。在中国， 艾滋病毒感染的确诊病例数量正在上升， 疾病的发病率高，了解脑血管病与HAND之间的关系尤为重要。 相关的这项计划拨款汇集了来自美国和中国的研究人员， 在中国资源有限的环境下进行HAND研究的能力，以实现我们的长期目标 目标是制定风险分层、预防和治疗艾滋病毒神经认知障碍的策略。我们将 利用加州大学旧金山分校弗朗西斯科系 神经内科和北京协和医院感染科，此外， 中国艾滋病临床试验组的研究基础设施，实施试点研究，旨在：（1） 估计HIV感染与经颅多普勒超声（TCD）评估的脑血管疾病的相关性 通过脑血管反应性测量内皮功能和（2）评估脑血管反应性与内皮功能之间的相关性。 血管反应性和脑损伤的标志物，包括小血管疾病，在横截面中的神经成像 接受治疗、病毒抑制的老年HIV感染者和人口统计学匹配的未感染对照者; (3)评估脑血管反应性与HAND和认知能力下降的相关性 接受治疗的病毒抑制老年HIV感染者和人口统计学匹配的未感染者队列 控制;和（4）发展人力资源和基础设施，以进行临床研究的手， 通过培训当地工作人员进行TCD和神经心理学测试以及临床 研究方法，制定和完善参与者招募，数据收集和 数据管理，并通过使用标准化协议和 质量保证。这项试点研究产生的数据和经验将为 R 01资助的中国HAND脑血管机制的确定性纵向队列研究 目的是鉴定疾病的潜在临床前标志物，确定 脑内皮功能与疾病严重程度和进展，并测试干预措施的有效性 在中国、美国和全世界的HIV人群中使用HAND改善脑内皮功能。