Tracking HIV Infection and Alcohol Abuse CNS Comorbidity with Neuroimaging

描述（由申请人提供）：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相互作用，以及抗HIV药物治疗进展延长寿命所引起的其他衰老并发症。除了这个老龄化的艾滋病毒感染者群体之外，50岁以上的新感染者人数也在增加。即使在相对健康的个体中，衰老的大脑也越来越容易受到内源性和外源性的伤害，一个例子是年龄-酒精中毒对脑组织体积和完整性的相互作用。同样，与年龄相关的神经系统完整性下降会加剧易受艾滋病毒感染的大脑系统，并增加患痴呆症的可能性。丙型肝炎感染（HVC）的常见合并症和艾滋病定义事件的后遗症进一步加剧了艾滋病毒感染的情况。因此，考虑到艾滋病毒感染人口的老龄化，对正常衰老、酒精使用障碍和艾滋病毒感染之间的相互作用的调查现在尤其重要。该提案建立在我们迄今为止的研究基础上，包括四组个体[HIV +酒精中毒（HIV+ALC），HIV无酒精中毒（HIV），酒精中毒（ALC），正常对照受试者（NCS）]，在8年内通过多模态神经成像[结构MRI和扩散张量成像（DTI）]，临床和行为评估以及神经心理学测试进行了5次以上的检查。我们的分析结果表明，衰老的大脑对艾滋病毒/艾滋病、酗酒和HCV感染的综合影响高度敏感。我们现在建议按照我们现有的100多名参与者的纵向队列（超过一半的人现在超过50岁），并招募另外100名年龄在50岁或以上的人，他们将以18个月的间隔接受神经成像[MRI，DTI，静息状态MRI（rsMRI）和脉冲连续动脉自旋标记（PCASL）测量的脑灌注]，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。目标1：通过MR成像和功能测量，在HIV感染和酒精滥用合并发病的老年人的扩大样本中建立脑病理学模式。横截面假设预测了一个复杂的模式的添加剂和相互作用的影响。目标二：通过每隔18个月测试当前和新队列，评估受酒精滥用、HCV感染和ART依从性调节的纵向疾病轨迹（进展或有效控制）。目标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受试者内的横截面和纵向关系。

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.