TRACKING HIV INFECTION AND ALCOHOL ABUSE CNS COMORBIDITY WITH NEUROIMAGING

描述(由申请人提供)：本申请是对RFA-AA-07-019：延续关于艾滋病毒感染和酗酒对中枢神经系统疾病的影响的合作协议的回应。其目的是利用先进的磁共振成像技术评估HIV感染和酒精滥用在体内的累积和进展效应，以调查长期饮酒和HIV感染对认知和大脑结构和功能完整性的单独和交互影响。由于危险饮酒是艾滋病毒感染者中的一个常见问题，因此研究这两种情况对大脑结构和功能的相加和交互影响是很重要的。长期目标是了解大量饮酒艾滋病毒感染者大脑结构和认知下降的机制，以开发更好的治疗这些认知和神经缺陷的方法。在过去的六年里，我们在一个不同种族的社区样本中评估了酒精滥用和艾滋病毒感染对大脑的累积和渐进的有害影响，该样本包括四组：高和低酒精消费的艾滋病毒感染者和高和低酒精消费的艾滋病毒血清阴性的受试者。对80%的入选样本进行了一年的随访，对75%的样本进行了三年的随访。研究开始时的横断面分析显示，与无症状的艾滋病毒感染患者相比，酗酒合并艾滋病毒感染的患者，特别是那些疾病进展为艾滋病的患者，存在大量的宏观、微观结构和生化方面的缺陷。这些发现在认知和运动表现以及自我评估的生活质量中得到了呼应。结构MRI的纵向分析表明，持续酗酒在进行性脑损伤中发挥着突出的作用，突出了检测和治疗合并酗酒患者的必要性。除了酒精滥用的协同负担外，数据还表明，性别和自我认同的种族作为检测大脑病理的重要因素具有显著影响。该计划未来五年的目标是：1)在艾滋病毒感染者和酒精滥用综合发病率的扩大样本中，建立使用磁共振成像和功能测量的脑病理模式；2)通过对当前队列的持续跟踪，评估受酒精滥用调控的纵向艾滋病毒疾病发展轨迹(进展或有效控制)，在研究进入后5至6年和7至8年进行测试；以及3)在神经成像测量、认知和运动表现以及临床状态之间建立横断面和纵向的受试者内部关系。

DESCRIPTION (provided by applicant): This application is in response to RFA-AA-07-019: Continuation of the Cooperative Agreement on the Interaction of HIV Infection and Alcohol Abuse on Central Nervous System Morbidity. The purpose is to evaluate the cumulative and progressive effects of combined HIV infection and alcohol abuse in vivo using advanced magnetic resonance imaging techniques to investigate the separate and interactive effects of chronic alcohol use and HIV infection on cognition and brain structural and functional integrity. Because hazardous alcohol use is a common problem among HIV infected individuals, it is important to study the additive and interactive effects of both conditions on brain structure and function. The long-term goal is to understand the mechanisms of the brain structural and cognitive decline in heavy drinking HIV-infected individuals to develop better treatments for these cognitive and neurological deficits. Over the past six years, we have evaluated the cumulative and progressive deleterious effects on the brain of combined alcohol abuse and HIV infection in an ethnically diverse community sample comprising four groups: high and low alcohol consuming HIV-infected subjects and high and low alcohol consuming HIV sero-negative subjects. One-year follow-up on 80% of the entry sample and three year follow-up on 75% have been completed. Cross-sectional analysis at study entry demonstrated substantial macrostructural, microstructural, and biochemical brain deficits in alcohol abusing patients with HIV infection, especially those whose disease had progressed to AIDS, compared with relative normality in asymptomatic HIV-infected patients. These findings are echoed in cognitive and motor performance and self-assessed quality of life. Longitudinal analyses of structural MRI indicate a prominent role for continued alcohol abuse in progressive brain damage, highlighting the need for detection and treatment of alcohol abuse in comorbid patients. In addition to the synergistic burden of alcohol abuse, the data also indicate significant effects of gender and self-identified ethnicity as important factors in detecting brain pathology. The objectives of the next five years of this program are to 1) establish the pattern of brain pathology with MR imaging and functional measures in an expanded sample of individuals with HIV infection and the combined morbidity of alcohol abuse; 2) assess longitudinal HIV disease trajectory (progression or effective control) as modulated by alcohol abuse by continuing follow-up of the current cohort, testing them at 5 to 6 and 7 to 8 years after study entry; and 3) establish cross-sectional and longitudinal within-subject relationships among neuroimaging measures, cognitive and motor performance, and clinical status.