Relationship of Cytokines to Cognitive Functions in HCV

细胞因子与 HCV 认知功能的关系

• 批准号: 7208222
• 负责人: ROBIN C HILSABECK
• 金额: $ 16.8万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-01 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7208222
• 关键词: Address; Affect; Alzheimer' s Disease; American; Attention; Biological Products; Chronic; Chronic Disease; Chronic Hepatitis C; Clinical; Cognition; Cognitive; Complex; Computers; Cytokine Network Pathway; Depressive disorder; Development; Electromyography; Environment; Equipment; Etiology; Exhibits; Functional disorder; Goals; HIV-1; Hand; Healthcare; Hepatitis C virus; Human Resources; Image; Immune response; Immune system; Immunologics; Impaired cognition; Individual; Infection; Infectious Disease Immunology; Inflammation; Interferon-alpha; Intervention; Investigation; Knowledge; Laboratories; Link; MCC protocol; Measurable; Measurement; Measures; Moods; Morbidity - disease rate; Motor Pathways; Neuraxis; Neuropsychological Tests; Neuropsychology; Participant; Patients; Pegylated Interferon Alfa; Persons; Positioning Attribute; Purpose; Relative (related person); Research; Research Methodology; Research Personnel; Research Training; Ribavirin; Robin bird; Role; Serum; Surface; Symptoms; Systemic Lupus Erythematosus; Testing; Thinking; Time; Training; Transcranial magnetic stimulation; Viral; Virus; Week; Work; career; cognitive function; comparison group; cytokine; disturbance in affect; experience; human disease; innovation; insight; interdisciplinary approach; mortality; neuroimmunology; neurophysiology; neuropsychiatry; patient oriented research; programs; skills; time interval

DESCRIPTION (provided by applicant): The candidate is a board certified clinical neuropsychologist with prior research experience examining cognitive functioning of patients with chronic hepatitis C. The research environment includes ample office and laboratory space, computers and testing equipment, administrative and technical personnel, and strong institutional support for devoting at least 75% time to career development in conducting patient-oriented research. The purpose of this application is to provide the candidate with the necessary training in viral neuroimmunology to become an independent researcher capable of investigating the relationship between the immune response and cognitive functioning. Career development will include both didactic and "hands on" training in viral neuroimmunology and research methodology associated with measurement of cytokines. The long-term goal is for the candidate to develop a programmatic line of research that will contribute to the limited understanding of how the immune system influences cognitive functioning. Specific Aims of this project are: 1) to test the hypothesis that higher levels of interferon-alpha (IFN-a), a proinflammatory cytokine, are associated with cognitive dysfunction in patients with chronic hepatitis C infection (CMC) as measured by neuropsychological tests, and 2) to test the hypothesis that higher levels of IFN-a are associated with cognitive dysfunction as indicated by inhibition of complex motor pathways in patients with CMC measured by image-guided, robotically positioned transcranial magnetic stimulation surface electromyography (irTMS-sEMG). CMC infection is associated with significant morbidity and mortality, including mood and cognitive disturbances. To complicate matters further, IFN-a, the primary treatment for CHC, also is associated with mood and cognitive disturbances. While much research has focused on mood disturbances associated with IFN-a therapy, far less attention has been paid to associated cognitive difficulties. In this study, patients with CHC will undergo neuropsychological testing, psychiatric assessment, cytokine measurement, and irTMS-sEMG within 1 month of beginning IFN-a therapy and again after 12 weeks of IFN-a therapy. Changes in cognitive functioning over time will be compared to that of a healthy comparison group tested over the same time interval. Levels of IFN-a and other cytokines in serum also will be examined and related to cognitive functioning. Knowledge gained by examining these relationships will increase understanding of how the immune response affects thinking abilities of patients with CHC and may provide insights into treatments for thinking problems. Additionally, these relationships may be true in patients with other chronic diseases that affect thinking, such as Alzheimer's disease and systemic lupus erythematosus, leading to possible treatments for these patients, as well.

描述（由申请人提供）：候选人是经过委员会认证的临床神经心理学家，具有检查慢性丙型肝炎患者认知功能的研究经验。研究环境包括充足的办公室和实验室空间、计算机和测试设备、行政和技术人员以及强有力的机构支持，以便在以患者为导向的研究中投入至少 75% 的时间用于职业发展。此应用程序的目的是为候选人提供必要的病毒神经免疫学培训，使其成为能够研究免疫反应与认知功能之间关系的独立研究人员。职业发展将包括病毒神经免疫学以及与细胞因子测量相关的研究方法方面的教学和“实践”培训。候选人的长期目标是开发一个有计划的研究路线，这将有助于对免疫系统如何影响认知功能的有限理解。该项目的具体目标是：1) 检验较高水平的干扰素-α (IFN-a)（一种促炎细胞因子）与通过神经心理学测试测量的慢性丙型肝炎感染 (CMC) 患者的认知功能障碍相关的假设，以及 2) 检验较高水平的 IFN-a 与认知功能障碍相关的假设（如以下所示） 通过图像引导、机器人定位的经颅磁刺激表面肌电图 (irTMS-sEMG) 测量 CMC 患者复杂运动通路的抑制。 CMC 感染与显着的发病率和死亡率相关，包括情绪和认知障碍。更复杂的是，CHC 的主要治疗方法 IFN-a 也与情绪和认知障碍有关。虽然许多研究都集中在与 IFN-α 治疗相关的情绪障碍上，但对相关认知困难的关注却少之又少。在这项研究中，CHC 患者将在开始 IFN-a 治疗后 1 个月内以及在 IFN-a 治疗 12 周后再次接受神经心理学测试、精神病学评估、细胞因子测量和 irTMS-sEMG。认知功能随时间的变化将与在相同时间间隔内测试的健康对照组的变化进行比较。血清中干扰素-α和其他细胞因子的水平也将被检查并与认知功能相关。通过检查这些关系获得的知识将增加对免疫反应如何影响 CHC 患者思维能力的理解，并可能为思维问题的治疗提供见解。此外，这些关系可能也适用于患有其他影响思维的慢性疾病的患者，例如阿尔茨海默病和系统性红斑狼疮，这也为这些患者提供了可能的治疗方法。