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中的影响以及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大脑成像方法，沿着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作用的因素，以及随着艾滋病毒感染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年龄和这些HIV相关因素而变化。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表明，艾滋病毒对大脑的影响与年龄有关，包括老年患者（>45岁）在基线时的缺陷更大，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，大脑结构的变化，如基底神经节和海马体积损失，在老年患者中以加速的速度发生，大脑变化与老年患者相似。最初的扩散张量成像（DTI）数据提供的证据表明，皮质下系统的结构完整性降低，这似乎是明显的发展之前，传统的MRI结构变化。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感染者（<> 45岁）与年轻和老年健康对照组（n=50）在36个月内的神经认知，神经影像学和实验室测量。所有人都将接受实验室检测，包括评估CD 4，病毒载量，以及血浆和CSF中的活化巨噬细胞。将在基线、12个月和36个月时获得脑结构成像（MPF和FLAIR）和DTI，沿着实验室和神经认知测量。研究结果将告诉我们HIV感染在大脑中的相互作用和随着时间的推移而衰老，将提供评估大脑结构变化的指标，将扩展我们对DTI在大脑疾病中的临床应用的知识，并可能导致HIV神经诊断学的进步。这项研究将提供有关艾滋病毒对大脑影响的有价值的信息。有关艾滋病毒对特定大脑结构的影响的知识将得到实现，并开发新的方法来评估这些变化。脑成像方法的临床应用，特别是MRI扩散张量成像，可能会出现，这可能会导致先进的诊断艾滋病毒在大脑中的影响。

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.