Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging

摘要 这项申请将建立在我们已建立的学习计划(R01AA017347)的基础上，并使其能够进行新的扩展， 用神经成像追踪HIV感染和酗酒的中枢神经系统共病。目前的提案旨在 加速HIV感染者大脑结构和功能与年龄相关的衰退的神经基质 感染(艾滋病毒)，特别是那些符合酒精使用障碍(AUD)标准的人。特别关注的是 到MRI可见的白质高信号(WMH)异常和非血红素性铁沉积，通常 发生在正常衰老中，并可能与疾病相互作用。水肿性组织标志--WHM 脱髓鞘在感染艾滋病毒的老年人中更为普遍，在那些 与正常衰老相关的AUD并存，并可能导致运动和认知障碍。同样，非- 皮质下和小脑齿状核中的血红素铁沉积随年龄增加而增加，这可能是 步态和平衡方面的障碍。平衡稳定性和认知能力是平行的还是加速的 有或没有AUD共病并与共同脑标志物相关的HIV的衰老轨迹仍然存在 不清楚。在这里，我们提出了一种纵向方案，使用一套神经成像方法来识别 我们假设局部组织退化的机制是姿势稳定性、步态、 男性和女性对HIV感染和AUD的认知情况。对这一人群的纵向研究将 确定大脑和行为缺陷是稳定的还是加速的，即表现出年龄和疾病的相互作用。 具体目标1：脑白质高信号(WMH)体积，使用流体-磁共振结构检测 衰减反转恢复(FLAIR)成像将被量化并区分为脑室周围 (PVWMH)或深部(DWMH)位于皮质叶、脑干和动脉区域。 具体目标2：将定量测量髓鞘完整性和局部铁沉积 磁化率图(QSM)和扩散张量成像(DTI)。非血红素铁将被量化为 皮质下灰质结构(苍白球、尾状核、壳核、 红核、齿状核)。QSM抗磁负磁化率结合DTI将用于 描述白质束和WMH中的组织成分。 具体目标3：静态姿势稳定性、动态步态和认知。静态姿势稳定将是 用平衡台测量，产生摇摆路径长度、摇摆方向和躯干震动的指标。步态 将被录像并在内部测量动态步态连贯性和稳定性的产出指标。 标准化的HIV相关神经认知障碍(手)综合得分将衡量组成部分 认知过程：执行功能，工作记忆/注意力，言语和视觉记忆和学习， 和空间能力。WMH容量、局部铁沉积和髓鞘破坏的影响将通过 我们对姿势稳定性的静态和动态测量以及认知的组成过程。

ABSTRACT This application will build on and enable novel extension of our established program of study (R01AA017347), "Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging." The current proposal seeks neural substrates that accelerate brain structural and functional age-related declines in people living with HIV infection (HIV), especially those who meet criteria for Alcohol Use Disorder (AUD). Particular attention is paid to MRI-visible anomalies of white matter hyperintensities (WMH) and non-heme iron deposition that commonly occur in normal aging and may interact with disease. WHM, markers of edematous tissue potentially marking demyelination, are more prevalent among older individuals with HIV infection and even greater in those comorbid with AUD relative to normal aging and may contribute to motor and cognitive deficits. Similarly, non- heme iron deposition in subcortical and cerebellar dentate nuclei increases with age and may underlie disturbance in gait and balance. Whether balance stability and cognitive abilities follow parallel or accelerated aging trajectories in HIV with or without AUD comorbidity and are related to common brain markers remain unclear. Herein, we propose a longitudinal protocol in using a suite of neuroimaging approaches to identify mechanisms of local tissue degradation we hypothesize underpin functional declines in postural stability, gait, and cognition of men and women aging with HIV infection and AUD. Longitudinal study of this population will determine if the brain and behavior deficits are stable or accelerating, i.e., exhibit an age-disease interaction. Specific Aim 1: White Matter Hyperintensity (WMH) volumes, detected with structural MRI using FLuid- Attenuated Inversion Recovery (FLAIR) imaging, will be quantified and distinguished as periventricular (PVWMH) or deep (DWMH) in cortical lobar, brain stem, and arterial regions. Specific Aim 2: Myelin Integrity and Regional Iron Deposition will be measured with Quantitative Susceptibility Mapping (QSM) and Diffusion Tensor Imaging (DTI). Non-heme iron will be quantified as paramagnetic positive susceptibility in subcortical gray matter structures (globus pallidum, caudate, putamen, red nucleus, dentate nucleus ). QSM diamagnetic negative susceptibility in combination with DTI will be used to characterize tissue constituents in white matter tracts and WMH. Specific Aim 3: Static Postural Stability, Dynamic Gait, and Cognition. Static postural stability will be measured with a balance platform yielding metrics of sway path length, sway direction, and truncal tremor. Gait will be video recorded and measured in-house yielding metrics of dynamic gait coherence and stability. Standardized HIV-Associated Neurocognitive Disorder (HAND) composite scores will measure component processes of cognition: executive function, working memory/attention, verbal and visual memory and learning, and spatial abilities. Impact of WMH volume, regional iron deposition, and myelin disruption will be tested with our static and dynamic measures of postural stability and with component processes of cognition.