Tracking HIV Infection and Alcohol Abuse CNS Comorbidity with Neuroimaging

描述(申请人提供)：本申请的目的是阐明HIV感染和酒精使用障碍对中枢神经系统发病率的交互作用，以及抗HIV药物疗法的进步所带来的延长寿命而引起的额外衰老并发症。除了这一老龄化的艾滋病毒感染队列，新感染艾滋病毒的50岁以上人群的数量也在不断增加。即使在相对健康的人中，老化的大脑也越来越容易受到内源性和外源性的侮辱，例如年龄与酒精中毒对脑组织体积和完整性的影响。同样，与年龄相关的神经系统完整性下降会加剧易感染艾滋病毒的大脑系统，增加患痴呆症的风险。使艾滋病毒感染情况进一步复杂化的是丙型肝炎感染(HVC)的常见共病和艾滋病定义事件的后遗症。因此，对正常衰老、酒精使用障碍和HIV感染之间的相互作用的研究现在尤其与老龄化的HIV感染人群密切相关。该建议基于我们迄今的研究，包括四组个体[HIV酒精中毒(HIV ALC)，HIV非酒精中毒(HIV)，酒精中毒(ALC)，正常对照组(NCS)]，在8年内通过多模式神经成像[结构MRI和扩散张量成像(DTI)]、临床和行为评估以及神经心理测试进行了5次以上的检查。我们的分析结果表明，老化的大脑对艾滋病毒/艾滋病、酒精中毒和丙型肝炎病毒感染的综合影响高度敏感。我们现在建议遵循我们现有的100多名参与者(其中一半以上现在超过50岁)的纵向队列，并再招募100名年龄在50岁或50岁以上的人，他们将每隔18个月接受一次神经成像[MRI、DTI、静息状态MRI(RsMRI)和脉冲持续动脉自旋标记(PCASL)测量的脑血流灌注]、临床、神经心理学和临床评估，包括测定循环促炎细胞因子水平。目的1：在HIV感染和酗酒合并发病的老年个体中，通过磁共振成像和功能测量建立脑病理模式。横截面假设预测了一种复杂的相加和交互效应模式。目的2：通过每隔18个月测试一次现有和新的队列，评估酒精滥用、丙型肝炎病毒感染和抗逆转录病毒治疗依从性所调节的纵向疾病轨迹(进展或有效控制)。目的3：在神经影像测量、认知和运动能力以及临床状态之间建立横断面和纵向的受试者之间的关系。

DESCRIPTION (provided by applicant): he purpose of this application is to elucidate the interaction of HIV infection and alcohol use disorders on central nervous system morbidity and the additional complications of aging arising from extended longevity afforded by advances in anti-HIV pharmacotherapies. Adding to this aging HIV-infected cohort are the increasing numbers of people over 50 years old who are being newly infected. Even in relatively healthy individuals, the aging brain is increasingly vulnerable to endogenous and exogenous insult, an example being the age-alcoholism interaction on brain tissue volume and integrity. Similarly, age-related decline in neural system integrity can compound the HIV-vulnerable brain systems and increase liability for dementia. Further compounding the picture of HIV infection is the common comorbidity of hepatitis C infection (HVC) and the sequelae of AIDS-defining events. Thus, investigation of interactions of normal aging, alcohol use disorders, and HIV infection is now especially germane given the aging HIV-infected population. The proposal builds on our research to date that includes individuals in four groups [HIV + Alcoholism (HIV+ALC), HIV without Alcoholism (HIV), Alcoholics (ALC), Normal Control Subjects (NCS)], examined upwards of 5 times over 8 years with multimodal neuroimaging [structural MRI and diffusion tensor imaging (DTI)], clinical and behavioral assessment, and neuropsychological testing. Results of our analyses demonstrate that the aging brain is highly sensitive to the combined effects of HIV/AIDS, alcoholism, and HCV infection. We now propose to follow our existing longitudinal cohort of over 100 participants (more than half of whom are now over 50 years old) and to recruit an additional 100 individuals age 50 or older who will be followed at 18-month intervals with neuroimaging [MRI, DTI, resting state MRI (rsMRI), and cerebral perfusion measured with pulsed-continuous arterial spin labeling (PCASL)], clinical, neuropsychological, and clinical assessment, including determination of circulating proinflammatory cytokine levels. Aim 1: Establish the pattern of brain pathology with MR imaging and functional measures in an expanded sample of older individuals with HIV infection and the combined morbidity of alcohol abuse. Cross-sectional hypotheses predict a complex pattern of additive and interactive effects. Aim 2: Assess longitudinal disease trajectory (progression or effective control) as modulated by alcohol abuse, HCV infection, and ART compliance by testing the current and new cohorts at 18-month intervals. Aim 3: Establish cross-sectional and longitudinal within-subject relationships among neuroimaging measures, cognitive and motor performance, and clinical status.