Mechanism and Predictors of Neurocognitive Impairment in HIV Infection

HIV 感染神经认知损伤的机制和预测因素

• 批准号: 10115127
• 负责人: Erin E O'Connor
• 金额: $ 18.93万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-03-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10115127
• 关键词: Accounting; Acquired Immunodeficiency Syndrome; Address; Adherence; Affect; Affective; Age; Age Factors; Aging; Area; Basal Ganglia; Behavioral; Blood Vessels; Brain; Caring; Cerebrovascular Circulation; Cerebrovascular Disorders; Chronic; Chronic Disease; Clinical; Clinical Research; Cognitive; Cohort Studies; Confounding Factors (Epidemiology); Data; Data Set; Diagnosis; Dimensions; Disease; Dropout; Elderly; Etiology; Evaluation; Female; Functional disorder; Future; Goals; Grant; HIV; HIV Infections; HIV-associated neurocognitive disorder; Hepatitis C co-infection; Image; Immune; Impairment; Individual; Inflammatory; Injury; Intervention; Knowledge; Lead; Life Expectancy; Measures; Medical; Mental Health; Mentors; Mentorship; Methods; Modeling; Monitor; Motor; Nature; Nerve Degeneration; Neuraxis; Neurocognitive Deficit; Neurologic; Neurologic Deficit; Neuropsychology; Outcome; Participant; Patients; Performance; Pharmaceutical Preparations; Physiology; Predisposition; Principal Investigator; Property; Public Health; Quality of life; Radiology Specialty; Research; Research Domain Criteria; Research Personnel; Research Project Grants; Research Training; Risk; Risk Factors; Sampling; Source; Structure; Techniques; Training; Validation; Viral; Viral Load result; Viral reservoir; Virus Diseases; Work; age effect; antiretroviral therapy; career; clinical practice; clinical risk; clinically relevant; clinically significant; co-infection; comorbidity; design; disability; disorder risk; experience; gray matter; male; mortality; multidisciplinary; multimodality; neural network; neuroimaging; neuroinflammation; neuromechanism; neurotoxic; neurovascular; precision medicine; predictive modeling; professor; prognostic; prospective; reconstitution; relating to nervous system; skills; statistics; substance use; systemic inflammatory response; white matter

As many as 50% of HIV infected patients develop HIV-associated neurocognitive disorder (HAND), despite treatment with antiretroviral therapy (ART). The number of affected patients may rise, given the increasing, and nearly normal, life expectancy of HIV patients. Fluctuating and sometimes declining neuropsychological performance in treated HIV patients are clinically significant because they may lead to decreased adherence to medication, higher mortality, poorer quality of life and mental health issues. The etiologies of these progressive neuropsychological changes are unclear, but may reflect dysfunction in a range of neural subsystems, including cortico-cortical, cortico-cerebellar or corticostriatal circuits that serve to integrate cognitive, motor and affective processing mechanisms. To study neuropsychological effects of HIV infection and its co-morbidities, we propose to differentiate HIV effects from five critical confounding factors: age, hepatitis C co-infection, ART type, systemic inflammation, and vascular risk. We will determine: (1) if multiple, compared to single, clinical and neuroimaging features can predict subsequent neuropsychological performance and (2) if longitudinal changes in brain structure and function provide evidence about the nature of the underlying neural mechanisms of observed performance changes. Using a Research Domain Criteria (RDoC) framework, we will focus on integrating performance measures from the cognitive and sensorimotor domains with underlying changes in brain structure and function. We are fortunate to have access to longitudinal data from the MACS, now known as the MACS/WIHS Combined Cohort Study, a large, well characterized sample of males and females that will allow us to identify changes in brain structure and function during HIV treatment. The research is significant because neuropsychological performance deficits remain prevalent in spite of widespread ART use and have significant public health implications. This project will allow identification of HIV patients who may benefit from medical care changes related to vascular risk or ART type. The Principal Investigator, Erin O’Connor MD, is an Assistant Professor of Radiology at UMSOM, whose long term career goal is to become an independent investigator in translational neuroradiology, focusing on imaging predictors of neuropsychological effects in neuroinflammatory, neurodegenerative and neurovascular disorders. To work towards this goal, we propose a research project designed to identify the neural mechanisms underlying HIV-related cognitive and motor disability. For this project, Dr. O’Connor will be mentored by a highly experienced neuroimaging team, including Dr. Chang, an HIV expert, Dr. Becker, an expert in HIV neuropsychology and aging, and Dr. Zeffiro, an expert in translational neuroimaging and statistics. The skills and analyses derived from this training grant will serve as the basis for a subsequent R01 proposal designed to validate predictors of neuropsychological change in treated HIV patients.

多达50％的艾滋病毒感染患者患有与HIV相关的神经认知障碍（手），dospite 抗逆转录病毒疗法（ART）治疗。鉴于增加，受影响的患者的数量可能会增加 艾滋病毒患者的预期寿命几乎是正常的。波动，有时神经心理学下降 治疗的艾滋病毒患者的表现在临床上具有重要意义，因为它们可能导致下降 遵守药物，更高的死亡率，较差的生活质量和心理健康问题。 这些进步性神经心理学变化的病因尚不清楚，但可能反映了 一系列神经元子系统的功能障碍，包括皮质皮质，皮质核或皮质纹状体 用于整合认知，运动和情感处理机制的电路。学习 艾滋病毒感染及其合并症的神经心理学影响，我们建议区分艾滋病毒效应 来自五个关键的混杂因素：年龄，丙型肝炎共感染，艺术类型，全身注射和 血管风险。我们将确定：（1）如果多个，与单个，临床和神经成像特征相比 预测随后的神经心理学表现和（2）如果大脑结构的纵向变化，并且 功能提供了有关观察性能的潜在神经机制的性质的证据 更改。使用研究领域标准（RDOC）框架，我们将专注于整合性能 来自认知和感觉运动领域的措施，大脑结构的潜在变化和 功能。我们很幸运能够从Mac中获取纵向数据，现在称为 Mac/WIHS组合队列研究，这是一个大型，表征的男性和女性样本，将 允许我们确定HIV治疗期间大脑结构和功能的变化。这项研究很重要 由于神经心理学的表现定义，尽管使用了宽度，但仍普遍存在 具有重大的公共卫生影响。该项目将允许识别可能的艾滋病毒患者 与血管风险或艺术类型有关的医疗保健变化受益。 首席研究员Erin O'Connor MD是UMSOM放射学助理教授， 他的长期职业目标是成为转化神经放射学领域的独立研究者， 专注于神经心理学效应在神经炎症，神经退行性和 神经血管疾病。为了实现这一目标，我们提出了一个研究项目，旨在确定 与HIV相关的认知和运动障碍背后的神经机制。对于这个项目，O'Connor博士将 由经验丰富的神经影像团队指导，包括艾滋病毒专家贝克（Becker）博士， 艾滋病毒神经心理学和衰老专家，以及转化神经影像学专家Zeffiro博士 统计数据。这项培训赠款得出的技能和分析将作为后续的基础 R01提出的旨在验证治疗艾滋病毒患者神经心理变化的预测因子。