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

基本信息

批准号：
9903280
负责人：
CHRISTINA S MEADE
金额：
$ 67.98万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-15 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9903280
关键词：
AIDS/HIV problem Acquired Immunodeficiency Syndrome Address Adult Affect Alcohol or Other Drugs use American Award Biological Markers Brain Brain Diseases Cannabis Chronic Classification Clinical Clinical assessments Cognitive Complex Coupling Data Development Diagnosis Diagnostic Disease Drug Addiction Drug Use Disorder Equilibrium Foundations Functional disorder Funding Goals Graph HIV HIV Infections HIV-associated cognitive impairment HIV-associated neurocognitive disorder Image 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 base 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 improved individual patient individualized medicine innovation marijuana use multidisciplinary multimodality nervous system disorder neural network neuroAIDS neurobehavioral neuroimaging neuromechanism novel organizational structure personalized predictions precision medicine predictive modeling programs public health relevance relating to nervous system response segregation sound stem white matter

项目摘要

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.

项目概要尽管广泛使用联合抗逆转录病毒疗法（cART），但近一半的艾滋病毒阳性美国人将经历与艾滋病毒相关的神经系统合并症，对日常功能和临床产生负面影响大脑结构和功能的改变始终与艾滋病毒相关的神经认知有关。疾病（HAND），但艾滋病毒引起神经网络改变的机制和相关的认知功能尚未得到很好的表征，而大麻的使用却异常普遍。 HIV+ 人群中，可能会增加 HAND 的风险。吸食大麻和艾滋病毒感染会加剧包括白质在内的主要神经网络的功能障碍异常和功能激活模式的解耦利用强大的基础。我们的多学科团队对吸毒成瘾和艾滋病毒/艾滋病的神经行为研究，提出了研究将应用连接组分析来实现以下目标：（1）检查独立和 (2) 研究艾滋病毒和大麻对大脑结构和功能组织的相互作用影响；大脑组织网络水平破坏与认知障碍之间的纵向关系； (3)利用机器深度学习算法开发用于HAND诊断的个性化预测模型使用交叉滞后面板设计，对 200 名成年人进行了分层。 HIV 和大麻状况（4 组）将在基线和 1 年进行多模式 MRI 和认知测试后来的中心假设是，吸食大麻会加剧大脑结构和功能的破坏。我们的提案直接响应 RFA-18-。 610，其中强调需要研究“滥用药物和艾滋病毒的潜在机制” 感染相互作用，通过改变的神经网络介导损害中枢神经系统功能。” 团队科学方法解决艾滋病指定资金的高优先主题，包括神经学并发症 [NOT-15-137] 建立在合理的前提和可靠的初步数据的基础上，这一创新。该项目具有识别适当的神经生物标志物的巨大潜力，这些生物标志物可能有助于诊断和治疗监测慢性物质使用障碍患者的 HAND，并作为临床新药物的目标此外，我们的分类模型有望提供一个可概括的框架。适用于个体患者，量身定制治疗方法。