Diffusion Tensor Imaging and Neuropsychological Outcomes in HIV/HCV Co-infection

描述（由申请人提供）：据估计，近三分之一的艾滋病毒阳性患者同时感染丙型肝炎病毒。对合并感染组的认知功能的研究发现，与单独感染HIV或HCV的组相比，在许多认知领域的神经心理学检查中表现更差（Cherner等人，2008；Clifford等人，2005；Hilsabeck等人，2005；Letendre等人，2002；Martin等人，2004；Parsons等人，2006；Ryan等人，2004；von Giesen等人，2004）。此外，据报道，合并感染者更有可能发展为艾滋病痴呆综合征（Ryan et al., 2004）。尽管合并感染中认知功能下降的研究结果一致，但迄今为止，还没有发表过使用神经影像学研究合并感染对中枢神经系统影响的报告。有一些已发表的研究使用MRI技术来确定HCV单一感染对大脑的影响；在HCV中应用磁共振波谱（MRS）的研究发现了与白质完整性破坏相关的标记物（Weissenborn等人列举了其他），类似于在HIV中的MRS发现。在HIV中使用弥散张量成像（DTI）的研究数量有限，结果表明白质受损，即使在看起来正常的白质中也是如此（Stebbins等，2007）。在合并感染中发现的神经心理缺陷和使用MRS在HCV中发现的类似结果虽然有限，但促使进一步的研究专门设计来检查合并感染对大脑的影响。需要采用对白质变化敏感的新型成像技术来确定合并感染中发生的损伤程度，这可能会导致早期诊断和改善神经症状的治疗。我们认为DTI是检查中枢神经系统合并感染的最佳工具，因为它对检测白质结构完整性的变化具有特定的敏感性。此外，由于并非所有的研究都确定了HCV合并感染状态对脑功能的显著影响，因此需要一种包括神经心理学评估、神经影像学指标和实验室数据在内的多学科方法。这项研究将比较HIV阳性个体和HIV/HCV合并感染个体的DTI测量样本，以及神经心理学测试，以确定大脑中合并感染的特征。拟议的研究将是第一个将这些地区具体纳入共同感染人群的研究。

DESCRIPTION (provided by applicant): It is estimated that almost a third of HIV-positive patients are co-infected with hepatitis C virus. Studies examining cognitive function in co-infected groups have found worse performance on neuropsychological examinations in a number of cognitive domains compared to groups with HIV or HCV alone (Cherner et al., 2008; Clifford et al., 2005; Hilsabeck,et al., 2005; Letendre et al., 2002; Martin et al., 2004; Parsons et al., 2006; Ryan et al., 2004; von Giesen et al., 2004). Additionally, it has been reported that co-infected persons are significantly more likely to develop AIDS dementia complex (Ryan et al., 2004). Despite the consistent findings of decreased cognitive functioning in co-infection, to date, there are no published reports using neuroimaging designed to study the impact of co-infection in the CNS. There are a few published studies using MRI techniques to determine the impact of HCV mono-infection on the brain; studies implementing Magnetic Resonance Spectroscopy (MRS) in HCV have found markers associated with the breakdown of white matter integrity (Weissenborn et. al list others) similar to MRS findings in HIV. There are a limited number of studies using diffusion tensor imaging (DTI) in HIV, with findings indicating white matter compromise, even in white matter that appears normal (Stebbins et al., 2007). The neuropsychological deficits found in co-infection and the similar findings in HCV using MRS, though limited, prompt additional research specifically designed to examine the effects co-infection on the brain. Novel imaging techniques that are sensitive to white matter changes need to be employed to determine the extent of injury that occurs in co-infection, and perhaps lead to earlier diagnosis and improved treatment of neurological symptoms. We believe DTI is the best tool to examine co-infection in the CNS, due to its specific sensitivity to detect changes in white matter structural integrity. Further, as not all studies have identified a significant effect of HCV co-infection status on brain function, a multidisciplinary approach is needed inclusive of neuropsychological assessment, neuroimaging indices and laboratory data. This study will compare a sample of HIV-positive individuals to HIV/HCV co-infected individuals on DTI measures, as well as neuropsychological tests, to determine the signatures of co-infection in the brain. The proposed study will be the first to integrate these areas specifically in a co-infected population. PUBLIC HEALTH RELEVANCE: A large percentage of individuals with HIV are co-infected with Hepatitis C; cognitive deficits have been found to be more severe deficits in this population. Current neuroimaging techniques indicate a breakdown of white matter in the brain. As not all studies have identified a significant effect of HCV co-infection status on brain function, a multidisciplinary approach is needed to determine the extent of injury that occurs in co-infection, and perhaps lead to earlier diagnosis and improved treatment of neurological symptoms. The proposed study will be the first to integrate neuropsychological assessment, neuroimaging indices and laboratory data in a co- infected population.