Role of cannabis on HIV-related cognitive impairment: a brain connectomics study

大麻对艾滋病毒相关认知障碍的作用：脑连接组学研究

• 批准号: 10596463
• 负责人: CHRISTINA S MEADE
• 金额: $ 5.31万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-15 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10596463
• 关键词: Acceleration; Acquired Immunodeficiency Syndrome; Address; Adult; Affect; American; Award; Biological Markers; Brain; Brain Diseases; Cannabis; Chronic; Classification; Clinical; Clinical assessments; Cognitive; Compensation; Complex; Coupling; Data; Development; Diagnosis; Diagnostic; Disease; Disease Progression; Drug Addiction; Drug Use Disorder; Equilibrium; Foundations; Functional disorder; Funding; Goals; Graph; HIV; HIV Infections; HIV-associated cognitive impairment; HIV-associated neurocognitive disorder; HIV/AIDS; Impaired cognition; Impairment; Intervention; Link; Longitudinal Studies; Magnetic Resonance Imaging; Marijuana; Mathematics; Mediating; Medical; Modeling; Monitor; Neurocognitive Deficit; Neurologic; Neurons; Neuropsychological Tests; Outcome; Participant; Pathway Analysis; Patients; Pattern; Persons; Property; Prospective Studies; Research; Research Proposals; Rest; Risk; Role; Science; Severities; Structure; Substance Use Disorder; Testing; Translational Research; Work; addiction; antiretroviral therapy; cannabinoid receptor; cognitive function; cognitive process; cognitive testing; cohort; comorbidity; connectome; connectome data; daily functioning; deep learning algorithm; design; diffusion weighted; drug of abuse; executive function; experience; follow-up; graph theory; imaging science; improved; individual patient; individualized medicine; innovation; marijuana use; multidisciplinary; multimodal neuroimaging; multimodality; nervous system disorder; neural; neural network; neuroAIDS; neurobehavioral; neuromechanism; novel; personalized predictions; polysubstance use; precision medicine; predictive modeling; programs; public health relevance; response; segregation; sound; stem; white matter

Project Summary Despite widespread use of combination antiretroviral therapy (cART), nearly half of HIV+ Americans will experience HIV-related neurological comorbidities that negatively impact daily functioning and clinical outcomes. Alterations in brain structure and function are consistently linked to HIV-associated neurocognitive disorders (HAND), but the mechanisms through which HIV causes alterations in neural networks and associated cognitive function are not well characterized. Marijuana use, which is disproportionately prevalent among HIV+ persons, may increase the risk of HAND. Our preliminary work suggests that co-occurring marijuana use and HIV infection intensifies dysfunction in major neural networks, including white matter abnormalities and decoupling of functional activation patterns. Capitalizing on a strong foundation of neurobehavioral research on drug addiction and HIV/AIDS by our multidisciplinary team, the proposed research will apply connectomic analyses to achieve the following aims: (1) examine the independent and interactive effects of HIV and marijuana on structural and functional organization of the brain; (2) investigate the longitudinal relationship between network-level disruptions in brain organization and cognitive impairment; and (3) use machine deep learning algorithms to develop individualized prediction models for HAND diagnosis and severity based on multimodal graph features. Using a cross-lagged panel design, 200 adults stratified by HIV and marijuana status (4 groups) will have multimodal MRIs and cognitive testing at baseline and 1 year later. The central hypothesis is that marijuana use will exacerbate structural and functional disruptions in brain organization that underlie the expression and progression of HAND. Our proposal responds directly to RFA-18- 610, which highlights the need for studies on “the underlying mechanisms whereby drugs of abuse and HIV infection interact to impair CNS functions mediated through altered neuronal networks.” This research uses a team science approach to address high priority topics for AIDS-designated funding, including neurological complications [NOT-15-137]. Building upon a sound premise and robust preliminary data, this innovative project has strong potential to identify appropriate neural biomarkers that may aid in the diagnosis and monitoring of HAND in persons with chronic substance use disorders and serve as targets for novel clinical interventions. In addition, our classification models are expected to provide a generalizable framework applicable to individual patients for tailoring of treatment approaches.

项目摘要 尽管使用抗逆转录病毒疗法（CART）的宽度范围，但几乎一半的HIV+美国人将 经验与HIV相关的神经系统合并症，对日常功能和临床的负面影响 结果。大脑结构和功能的改变始终与HIV相关的神经认知有关 疾病（手），但艾滋病毒引起神经网络的改变的机制和 相关的认知功能没有很好地表征。大麻的使用，这是普遍不成比例的 在艾滋病毒+人中，可能会增加手动风险。我们的初步工作表明共同出现 大麻使用和HIV感染加剧了主要神经网络的功能障碍，包括白质 功能激活模式的异常和脱钩。利用强大的基础 我们的多学科团队对药物成瘾和艾滋病毒/艾滋病的神经行为研究，提议 研究将应用连接元分析以实现以下目的：（1）检查独立和 艾滋病毒和大麻对大脑结构和功能组织的交互作用； （2）调查 大脑组织中的网络级破坏与认知障碍之间的纵向关系； （3）使用机器深度学习算法来开发手动诊断的个性化预测模型 和基于多模式图特征的严重性。使用跨滞后面板设计，200名成年人分层 艾滋病毒和大麻状态（4组）将在基线和1年进行多模式MRI和认知测试 之后。中心假设是，大麻的使用会加剧大脑的结构和功能破坏 组织的组织是手的表达和进展。我们的建议直接回应RFA-18- 610，强调了对虐待和艾滋病毒药物的基本机制进行研究的需求 感染相互作用以损害通过改变神经元网络介导的CNS功能。”该研究使用 团队科学方法来解决艾滋病指定资金的高优先级主题，包括神经学 并发症[非15-137]。以合理的前提和强大的初步数据为基础，这种创新性 项目具有巨大的潜力，可以识别适当的神经生物标志物，以帮助诊断和 监测患有慢性药物使用障碍的人的手，并作为新型临床的靶标 干预措施。此外，我们的分类模型有望提供一个可推广的框架 适用于个别患者的治疗方法。