Tracking HIV Infection and Alcohol Abuse CNS Comorbidity with Neuroimaging

通过神经影像学追踪 HIV 感染和酒精滥用中枢神经系统合并症

• 批准号: 9532537
• 负责人: Adolf Pfefferbaum
• 金额: $ 28.5万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9532537
• 关键词: AIDS diagnosis; AIDS/HIV problem; Acceleration; Acquired Immunodeficiency Syndrome; Adverse effects; Affect; Age; Age-Years; Aging; Alcohol abuse; Alcohol dependence; Alcoholism; Anti-Retroviral Agents; Behavior assessment; Brain; Brain Pathology; CD4 Lymphocyte Count; Cerebrum; Cessation of life; Chronic; Clinical; Clinical assessments; Cognitive; Comorbidity; Complex; Dementia; Deterioration; Diffuse; Diffusion Magnetic Resonance Imaging; Disease; Early treatment; Epidemic; Event; Exhibits; Face; Fiber; HIV; HIV Infections; Health; Hepatitis C; High Prevalence; Incidence; Individual; Infection; Investigation; Longevity; Longitudinal cohort; Magnetic Resonance Imaging; Maintenance; Measures; Morbidity - disease rate; Motor; Neuraxis; Neuropsychological Tests; Neuropsychology; Participant; Patients; Pattern; Performance; Perfusion; Pharmaceutical Preparations; Pharmacotherapy; Physiologic pulse; Population; Recruitment Activity; Research; Rest; Sampling; Spin Labels; Structure; System; Testing; Time; age related; aging brain; alcohol use disorder; brain tissue; brain volume; co-infection; cohort; compliance behavior; cytokine; drinking; experience; frailty; improved; indexing; multimodality; neuroimaging; normal aging; problem drinker; relating to nervous system; sobriety; white matter; young adult

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.

描述（由申请人提供）：本申请的目的是阐明中枢神经系统发病率上的艾滋病毒感染和酒精使用障碍的相互作用，以及抗HIV药物治疗的进步所提供的延长寿命引起的衰老并发症。增加了艾滋病毒感染的人群的增长是，越来越多的50岁以上的人被新近感染。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侮辱的影响，一个例子是关于脑组织体积和完整性的年龄 - 酒精中毒相互作用。同样，神经系统完整性与年龄相关的下降可以使HIV侵蚀性的大脑系统加剧，并增加痴呆症的责任。肝炎感染（HVC）的常见合并症和艾滋病定义事件的后遗症的常见合并症。因此，鉴于衰老的HIV感染人群，对正常衰老，酒精使用障碍和HIV感染的相互作用的研究尤其是德国人。该提案基于我们迄今为止的研究，其中包括四组[HIV +酒精中毒（HIV + ALC），没有酒精中毒的HIV（HIV），酒精中毒（ALC），正常对照受试者（NCS）]，在8年内进行了5次多模态神经成像[结构MRI和散射tensor tensor tensor tensor and Issigity and Issigy and Issigy and Cancy and Cancy and Cancy and Cancy]，并进行了5倍以上。我们的分析结果表明，衰老的大脑对HIV/AIDS，酒精中毒和HCV感染的综合作用高度敏感。 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,神经心理学和临床评估，包括确定循环促炎细胞因子水平。 AIM 1：在艾滋病毒感染的老年人的扩大样本和酒精滥用的综合发病率的扩展样本中，通过MR成像和功能度量建立脑病理学模式。横截面假设预测了累加和互动效应的复杂模式。 AIM 2：通过以18个月的间隔测试当前和新队列，评估受酒精滥用，HCV感染和艺术依从性调节的纵向疾病轨迹（进展或有效控制）。目标3：在神经成像措施，认知和运动表现以及临床状态之间建立横截面和纵向内部关系。