Age Effects on HIV-associated Brain Dysfunction

描述（由申请人提供）：拟议的研究是调查艾滋病毒在大脑和神经认知功能的影响，随着人们年龄的增长。该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，以及随着艾滋病毒感染患者年龄的增长而发生的变化。我们将研究神经认知结果和大脑结构变化如何随着年龄和这些hiv相关因素的变化而变化。纵向实验设计将采用统计建模方法来描述随时间的变化。来自我们实验室的最新数据指出了HIV在大脑中的年龄相关影响，包括老年患者（45岁以上）在基线时的缺陷更大，随着时间的推移变化更大的证据。此外，我们的数据表明，老年患者的大脑结构变化，如基底神经节和海马体积损失，发生的速度加快，与老年患者的大脑变化相似。初始弥散张量成像（DTI）数据提供了皮层下系统结构完整性降低的证据，这在传统MRI上的结构变化发展之前就很明显。拟议的研究将扩展这些初步研究结果；比较年轻和老年（n= 120） hiv感染患者（< 45岁）与匹配队列的年轻和老年健康对照（n=50）在36个月内的神经认知、神经影像学和实验室测量。所有患者都将接受实验室检测，包括评估CD4、病毒载量、血浆和脑脊液中活化的巨噬细胞。将在基线、12个月和36个月时获得结构脑成像（MPRAGE和FLAIR）和DTI，以及实验室和神经认知测量。这些结果将告诉我们大脑中HIV感染与衰老之间的相互作用，将为评估大脑结构变化提供指标，将扩展我们对DTI在脑部疾病中的临床应用的了解，并可能导致HIV神经诊断的进展。这项研究将提供有价值的信息，关于艾滋病毒对大脑的影响，随着年龄的增长。随着评估这些变化的新方法的开发，有关艾滋病毒对特定大脑结构影响的知识将得到实现。可能出现脑成像方法的临床应用，特别是MRI弥散张量成像，这可能导致艾滋病毒对大脑影响的诊断取得进展。

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.