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艾滋病毒感染和酒精使用障碍对中枢神经系统发病率的相互作用，以及抗艾滋病毒药物治疗的进步所带来的寿命延长所带来的额外衰老并发症。除了这一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不断增加。即使在相对健康的个体中，老化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影响。同样，与年龄相关的神经系统完整性下降会使易受艾滋病毒感染的大脑系统复杂化，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使艾滋病毒感染的情况进一步复杂化。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相互作用的调查现在尤为重要。该建议建立在我们迄今为止的研究基础上，该研究包括四组个体[HIV +酒精中毒（HIV+ALC）， HIV非酒精中毒（HIV），酗酒者（ALC），正常对照受试者（NCS）]，在8年中通过多模态神经成像[结构MRI和弥散张量成像（DTI）]进行了5次以上的检查，临床和行为评估以及神经心理测试。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。我们现在建议继续我们现有的100多名参与者的纵向队列研究（其中一半以上的人现在已经超过50岁），并招募另外100名年龄在50岁或以上的人，每隔18个月对他们进行神经影像学随访[MRI， DTI，静息状态MRI (rsMRI)，以及用脉冲连续动脉自旋标记（PCASL）测量脑灌注]，临床，神经心理学和临床评估。包括循环促炎细胞因子水平的测定。目的1：在艾滋病毒感染和酒精滥用合并发病率的老年人扩大样本中，通过磁共振成像和功能测量建立脑病理模式。横断面假设预测了叠加和相互作用的复杂模式。目的2：通过每隔18个月对当前和新队列进行测试，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横断面和纵向的受试者关系。

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.