Alcohol and HIV-associated Brain Dysfunction

酒精和艾滋病毒相关的脑功能障碍

• 批准号: 7842295
• 负责人: RONALD A COHEN
• 金额: $ 43.78万
• 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/7842295
• 关键词: AIDS Dementia Complex; Accounting; Address; Adherence; Affect; Alcohol consumption; Alcohols; Amino Acids; Anisotropy; Anti-Retroviral Agents; Area; Arts; Basal Ganglia; Biological Markers; Brain; Brain Diseases; Brain imaging; Brain region; Cerebrospinal Fluid; Cerebrum; Choline; Chronic; Clinical; Comorbidity; Consumption; Corpus Callosum; Counseling; Creatinine; 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; 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; 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.

大量饮酒 (ETOH) 会影响肝脏和大脑。其对大脑的影响可能会因相关的肝脏疾病而加剧 和代谢紊乱，包括胰岛素抵抗、氧化应激和线粒体功能障碍。拟议的 研究将调查 ETOH 消耗对 HIV 相关脑功能障碍的影响。该研究包括 最先进的脑成像方法以及临床和实验室方法来评估交互作用 HIV 感染、乙醇消耗和肝功能障碍的影响。我们将研究神经认知结果如何 大脑结构的变化随 ETOH 消耗、特定代谢紊乱的程度、 和艾滋病毒相关因素。将采用纵向实验设计和统计建模方法 描述随时间变化的特征。我们实验室的最新数据表明，艾滋病毒与酒精相关的影响 大脑，包括证据表明消耗大量 ETOH 的人在基线和 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 作为这些因素相互作用的函数，皮质体积损失以加​​速的速度发生。扩散张量 想象（DTI）数据提供了皮层下系统结构完整性降低的证据，这似乎是 在传统 MRI 结构变化发生之前就很明显。磁共振波谱 (MRS) 研究结果表明，大脑代谢物水平的增加反映了炎症过程，也反映了神经元的代谢水平。 损伤，特别是基底神经节的损伤，还有白质和皮质区域的损伤。这些异常现象在 大脑与 HIV 和 ETOH 都有联系，尽管这两个因素如何随着时间的推移相互作用，导致大脑发生变化。 大脑的结构和功能尚不清楚。拟议的研究将比较艾滋病毒感染者和血清阴性者 根据 ETOH 使用情况将对照患者分为三组（重度 ETOH 使用、中度使用 使用 ETOH（使用 ETOH，不使用 ETOH），接受超过 36 个月的神经认知、神经影像和实验室评估 措施。所有这些都将接受实验室测试，包括评估 CD4、病毒载量、激活的巨噬细胞 血浆和脑脊液，以及肝脏、胰岛素和代谢功能的测量。神经影像、实验室和神经认知 评估将在基线、12 个月和 36 个月时进行。结果将告诉我们有关交互的信息 大脑中的 ETOH 和 HIV，并提供评估大脑结构和代谢变化的指标，可能 扩展这些方法在脑部疾病中的临床应用，可能会导致神经诊断的进步 HIV 患者，包括将 HIV 影响与其他共病因素（尤其是 ETOH）区分开来的方法 消耗和肝脏疾病。