Age Effects on HIV-associated Brain Dysfunction

描述(申请人提供)：这项拟议的研究是为了调查艾滋病毒在大脑中的影响&随着人们年龄的增长，对神经认知功能的影响。这项研究结合了最先进的脑成像方法以及艾滋病毒感染的临床和实验室措施。目标是更好地了解影响艾滋病毒在大脑中的作用的因素，这些因素有助于随着艾滋病毒感染患者的年龄而发生变化。我们将研究神经认知结果和大脑结构变化是如何随着年龄的变化而变化的&这些与艾滋病毒相关的因素。将采用纵向实验设计和统计建模方法来表征随时间的变化。我们实验室的最新数据指出了艾滋病毒对大脑的年龄相关影响，包括有证据表明，年龄较大的患者(45岁)在基线水平上有更大的缺陷，随着时间的推移，变化比年轻患者更大。此外，我们的数据表明，大脑的结构性变化，如基底节和海马体体积的丧失，在老年患者中以加速的速度发生，大脑变化与高龄患者相似。初始扩散张量成像(DTI)数据提供了皮质下系统结构完整性降低的证据，这似乎在传统MRI结构变化发生之前就很明显。这项拟议的研究将扩展这些初步发现，将年轻和老年(n=120)HIV感染患者(45岁)与匹配的年轻和老年健康对照组(n=50)在神经认知、神经成像和实验室测量方面进行36个月的比较。所有患者都将接受实验室测试，包括评估CD4、病毒载量和血浆和脑脊液中激活的巨噬细胞。结构脑成像(MPRAGE和FLAIR)和DTI将在基线、12个月和36个月获得，以及实验室和神经认知测量。这一结果将使我们了解HIV感染与衰老在大脑中的相互作用，将为评估大脑结构变化提供指标，将扩大我们对DTI在脑部疾病临床应用的了解，并可能导致HIV神经诊断的进步。这项研究将提供有关艾滋病毒随着年龄增长对大脑影响的有价值的信息。通过开发评估这些变化的新方法，将获得关于艾滋病毒对特定大脑结构的影响的知识。脑成像方法的临床应用，尤其是MRI扩散张量成像，可能会导致对HIV在大脑中的影响的诊断方面的进步。

DESCRIPTION (provided by applicant): The proposed study is to investigate the effects of HIV in the brain & on neurocognitive functioning as people age. The study incorporates state-of-the-art brain imaging methods along with clinical & laboratory measures of HIV infection. The goal is to achieve greater understanding of factors that influence HIV effects in the brain, & that contribute to changes that occur as HIV-infected patients' age. We will examine how neurocognitive outcome & structural brain changes vary as a function of age & these HIV-associated factors. A longitudinal experimental design will be employed with statistical modeling methods to characterize changes over time. Recent data from our laboratory points to age-associated effects of HIV in the brain, including evidence that older patients (>45 years) have greater deficits at baseline & greater change over time than younger patients. Furthermore, our data suggests that structural brain changes, such as basal ganglia & hippocampal volume loss occur at an accelerated rate in older patients, with brain changes similar to those seen with advanced age. Initial diffusion tensor imagining (DTI) data provides evidence of reduced structural integrity of subcortical systems that appears to evident prior to the development of structural changes on traditional MRI. The proposed study will extend these preliminary findings; comparing young & older (n =120) HIV-infected patients (<> 45 years) with matched cohorts of young & older healthy controls (n=50) over 36-months on neurocognitive, neuroimaging, & laboratory measures. All will undergo laboratory testing including assessment of CD4, viral load, & activated macrophages from plasma & CSF. Structural brain imaging (MPRAGE & FLAIR) & DTI will be acquired at baseline, 12 months, & 36-months, along with the laboratory & neurocognitive measures. The results will inform us about the interaction of HIV infection in the brain & aging over time, will provide metrics for assessing structural brain changes, will extend our knowledge of the clinical application of DTI for brain disorders & may lead to advances in neurodiagnostics for HIV. This study will provide valuable information about the effects of HIV on brain as people age. Knowledge about HIV effects on specific brain structures will be achieved, with new methods developed for assessing these changes. Clinical application of brain imaging methods, most notably in particular MRI diffusion tensor imaging, may occur, which may lead to advanced in diagnostics for HIV effects in the brain.