Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging

摘要 本申请将建立在我们既定研究项目（R 01 AA 017347）的基础上，并实现新的扩展， “追踪HIV感染和酒精滥用CNS并发症与神经影像学。“目前的提案寻求 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（HIV），特别是那些符合酒精使用障碍（AUD）标准的人。特别注意 MRI可见白色物质高信号（WMH）和非血红素铁沉积异常， 发生在正常衰老中，并可能与疾病相互作用。WHM，水肿组织的标记物，可能标记 脱髓鞘，在感染艾滋病毒的老年人中更为普遍，在那些 相对于正常衰老，与AUD共病，可能导致运动和认知缺陷。同样，非- 皮质下和小脑齿状核血红素铁沉积随年龄增加而增加， 步态和平衡障碍。平衡稳定性和认知能力是并行还是加速 HIV伴或不伴AUD合并症的衰老轨迹与常见的脑标志物相关， 不清楚在此，我们提出了一个纵向协议，使用一套神经影像学方法，以确定 我们假设局部组织退化的机制支持姿势稳定性，步态， 艾滋病病毒感染者和老年人对AUD的认知。对这一人群的纵向研究将 确定大脑和行为缺陷是否稳定或加速，即，显示出年龄与疾病的相互作用。 具体目标1：使用FLuid-通过结构MRI检测的白色高信号（WMH）体积 衰减反转恢复（FLAIR）成像将被量化并区分为脑室周围 在皮质叶、脑干和动脉区域中存在PVWMH或深部DWMH。 具体目标2：将使用定量分析仪测量髓鞘完整性和局部铁沉积 磁敏感性成像（QSM）和扩散张量成像（DTI）。非血红素铁将被定量为 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 表征白色物质束和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。静态姿势稳定性 用平衡平台测量，产生摇摆路径长度、摇摆方向和躯干震颤的度量。步态 将进行视频记录，并在内部测量动态步态一致性和稳定性的指标。 标准化HIV相关神经认知障碍（HAND）综合评分将测量 认知过程：执行功能、工作记忆/注意力、语言和视觉记忆和学习， 空间能力。WMH体积、局部铁沉积和髓磷脂破坏的影响将通过 我们的静态和动态措施的姿势稳定性和组成过程的认知。

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.