Alcohol and HIV-associated Brain Dysfunction

酒精和艾滋病毒相关的脑功能障碍

• 批准号: 8379796
• 负责人: RONALD A COHEN
• 金额: $ 39.06万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8379796
• 关键词: AIDS Dementia Complex; Accounting; Address; Adherence; Affect; Alcohol abuse; Alcohol consumption; Alcohols; Amino Acids; Anisotropy; Anti-Retroviral Agents; Area; Basal Ganglia; Biological Markers; Brain; Brain Diseases; Brain imaging; Brain region; Cerebrospinal Fluid; Cerebrum; Choline; Chronic; Clinical; Comorbidity; Consumption; Corpus Callosum; Counseling; Creatinine; DNA; Data; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Encephalitis; Ethanol; Experimental Designs; Functional disorder; Glucose; Goals; HIV; HIV Infections; Health Status; Hepatic; Hepatitis C; Hippocampus (Brain); Impairment; Individual; Infection; Inflammatory; Insulin; Insulin Resistance; Internal Capsule; Intervention; Investigation; Laboratories; Lead; Leukoencephalopathy; Life; Link; Liver; Liver Dysfunction; Liver diseases; Longitudinal Studies; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measures; Mediating; Metabolic; Methods; Metric; N-acetylaspartate; Nature; Nerve Degeneration; Neurocognitive; Neurons; Outcome; Oxidative Stress; Parietal; Participant; Pathway interactions; Patients; Performance; Peripheral; Plasma; Process; Recording of previous events; Relative (related person); Research; Risk; Secondary to; Statistical Models; Structure; System; Testing; Thalamic structure; Thick; Time; Viral; Viral Load result; alcohol abstinence; alcohol exposure; base; biobehavior; brain volume; chemokine; clinical application; cognitive function; cohort; design; experience; functional outcomes; high risk behavior; imaging modality; improved; indexing; interest; liver function; macrophage; mitochondrial dysfunction; morphometry; myoinositol; neuroimaging; prevent; putamen; stem; white matter

Heavy alcohol (ETOH) use affects both liver and brain. Its effects on brain may be aggravated by associated hepatic and metabolic disturbances, including insulin resistance, oxidative stress, and mitochondrial dysfunction. The proposed study will investigate effects of ETOH consumption on HIV-associated brain dysfunction. The study incorporates state-of-the-art brain imaging methods along with clinical and laboratory methods to assess interactive effects of HIV infection, ETOH consumption, and hepatic dysfunction. We will examine how neurocognitive outcome and structural brain changes vary as a function of ETOH consumption, the extent of specific metabolic disturbances, and HIV-associated factors. A longitudinal experimental design will be employed with statistical modeling methods to characterize changes over time. Recent data from our laboratory point to alcohol-associated effects of HIV in the brain, including evidence that people who consume large quantities of ETOH have greater deficits at baseline and greater change over time than non users. Furthermore, our data suggest that basal ganglia, hippocampal, and cortical volume loss occur at an accelerated rate as a function of the interaction of these factors. Diffusion tensor imagining (DTI) data provide evidence of reduced structural integrity of subcortical systems that appears to be evident prior to development of structural changes on traditional MRI. Magnetic resonance spectroscopy (MRS) findings point to both increased brain metabolite levels reflecting inflammatory processes and also neuronal damage, particularly in the basal ganglia, but also in white matter and cortical areas. These abnormalities in the brain have been linked to both HIV and ETOH, though how these two factors interact over time to cause changes in brain structure and function is not well understood. The proposed study will compare HIV-infected and seronegative control patients who have been stratified into three groups based oh their ETOH use (Heavy ETOH use, moderate ETOH use, no-ETOH) who are assessed over 36 months on neurocognitive, neuroimaging, and laboratory measures. All will undergo laboratory testing including assessment of CD4, viral load, activated macrophages from plasma and CSF, and measures of liver, insulin, and metabolic function. Neuroimaging, laboratory, and neurocognitive assessment will be conducted at baseline, 12 and 36 months. Results will inform us about the interaction of ETOH and HIV in the brain, and provide metrics for assessing structural and metabolic brain changes, potentially extending the clinical application ofthese methods for brain disorders that may lead to neurodiagnostic advances for patients with HIV, including methods for dissociating effects of HIV from other co-morbid factors, most notably ETOH consumption and liver disease.

大量酒精（ETOH）的使用会影响肝脏和大脑。相关的肝脏可能会加剧其对大脑的影响 以及代谢性障碍，包括胰岛素抵抗，氧化应激和线粒体功能障碍。提议 研究将研究ETOH消耗对HIV相关脑功能障碍的影响。该研究合并 最先进的脑成像方法以及临床和实验室方法来评估互动性 HIV感染，ETOH消耗和肝功能障碍的影响。我们将研究神经认知的结果 结构大脑随着ETOH消耗的函数而变化，特定代谢障碍的程度， 和与HIV相关的因素。纵向实验设计将采用统计建模方法进行 表征随着时间的变化。从我们的实验室点到艾滋病毒与酒精相关的影响的最新数据 大脑，包括证据表明，在基线和 随着时间的推移，变化比非用户更大。此外，我们的数据表明基底神经节，海马和 皮质体积损失以加​​速速率发生，这是这些因素相互作用的函数。扩散张量 想象（DTI）数据提供了降低皮层系统结构完整性的证据，这似乎是 在开发传统MRI的结构变化之前很明显。磁共振光谱（MRS） 发现表明，脑代谢物水平增加，反映炎症过程和神经元 损坏，尤其是在基底神经节中，也是白质和皮质区域。这些异常 大脑与HIV和ETOH都相关，尽管这两个因素如何随着时间的流逝而相互作用以引起变化 大脑的结构和功能尚不清楚。拟议的研究将比较感染HIV的和血清负格的 对照患者分为三组的OH使用，他们的ETOH使用（大量使用ETOH，中度 在36个月内，对神经认知，神经影像学和实验室进行了36个月的评估，使用ETOH）。 措施。所有人将接受实验室测试，包括评估CD4，病毒载荷，激活的巨噬细胞 血浆和CSF，以及肝脏，胰岛素和代谢功能的测量。神经影像学，实验室和神经认知 评估将在基线，12个月和36个月进行。结果将告知我们有关互动的 大脑中的EtOH和HIV的摄 扩展这些方法在脑疾病中的临床应用可能导致神经诊断的进步 艾滋病毒的患者，包括与其他合并因素分离HIV作用的方法，最著名的是ETOH 食用和肝病。