TRACKING HIV INFECTION AND ALCOHOL ABUSE CNS COMORBIDITY WITH NEUROIMAGING

描述（由申请方提供）：本申请是对RFA-AA-07-019：延续关于HIV感染和酒精滥用对中枢神经系统疾病相互作用的合作协议的回应。本研究的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行性影响，以研究慢性酒精使用和HIV感染对认知和大脑结构和功能完整性的单独和相互作用。由于危险的酒精使用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叠加和交互作用非常重要。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能力下降的机制，以开发更好的治疗这些认知和神经缺陷的方法。在过去的六年中，我们已经评估了在一个种族多样化的社区样本，包括四组：高和低酒精消费的艾滋病毒感染的受试者和高和低酒精消费的艾滋病毒血清阴性受试者的酒精滥用和艾滋病毒感染相结合的大脑的累积和渐进的有害影响。对80%的入组样本进行了1年随访，对75%的入组样本进行了3年随访。研究开始时的横断面分析表明，与无症状HIV感染患者的相对正常相比，HIV感染的酒精滥用患者，特别是那些疾病进展为AIDS的患者，存在大量的宏观结构、微观结构和生化脑缺陷。这些发现与认知和运动表现以及自我评估的生活质量相呼应。结构MRI的纵向分析表明，持续的酒精滥用在进行性脑损伤中的重要作用，强调了对共病患者酒精滥用的检测和治疗的必要性。除了酒精滥用的协同负担外，数据还表明性别和自我认定的种族是检测大脑病理学的重要因素。该计划未来五年的目标是：1）在扩大的艾滋病毒感染者和酗酒合并发病率样本中，通过MR成像和功能测量建立脑病理学模式; 2）评估艾滋病毒疾病的纵向轨迹（进展或有效控制），通过对当前队列的持续随访，在进入研究后5 - 6年和7 - 8年对他们进行测试; 3）在神经影像学测量、认知和运动表现以及临床状态之间建立横向和纵向受试者内关系。

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.