Tracking HIV Infection & Alcohol Abuse CNS Comorbidity with Neuroimaging

追踪艾滋病毒感染

• 批准号: 10755558
• 负责人: Adolf Pfefferbaum
• 金额: $ 92.34万
• 依托单位: SRI INTERNATIONAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2028-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10755558
• 关键词: Acceleration; Age; Aging; Alcohol abuse; Algorithmic Analysis; Anisotropy; Attention; Attenuated; Behavior; Blood Pressure; Brain; Brain Stem; Characteristics; Cognition; Cognitive; Cognitive deficits; Cross-Sectional Studies; Demyelinations; Dentate nucleus; Deposition; Deterioration; Diagnosis; Diagnostic; Diffusion Magnetic Resonance Imaging; Disease; Equilibrium; Exhibits; Gait; Globus Pallidus; HIV; HIV Infections; HIV-associated neurocognitive disorder; Image; Impaired cognition; Individual; Iron; Length; Liquid substance; Lobar; Longevity; Longitudinal Studies; Magnetic Resonance; Magnetic Resonance Imaging; Maps; Measures; Motor; Movement; Myelin; National Institute on Alcohol Abuse and Alcoholism; Participant; Pathology; Persons; Population; Posture; Predisposition; Prevention; Process; Protocols documentation; Radial; Recovery; Red nucleus structure; Short-Term Memory; Standardization; Structure; Testing; Tissues; Tremor; Ventricular; Video Recording; Virus Diseases; White Matter Hyperintensity; Woman; Writing; age related; alcohol use disorder; brain tissue; cognitive ability; comorbidity; disorder control; executive function; frailty; functional decline; gray matter; high body mass index; indexing; insight; longitudinal analysis; men; motor deficit; neural; neuroimaging; normal aging; novel; programs; putamen; response; success; verbal; visual learning; visual memory; white matter

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.

抽象的 该应用程序将建立在我们已建立的研究计划（R01AA017347）的基础上并实现新的扩展， “通过神经影像学追踪 HIV 感染和酒精滥用中枢神经系统合并症。”目前的提案寻求 加速艾滋病毒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），尤其是那些符合酒精使用障碍（AUD）标准的人。特别注意 MRI 可见的白质高信号 (WMH) 和非血红素铁沉积异常，通常 发生在正常衰老过程中，并可能与疾病相互作用。 WHM，水肿组织潜在标记的标记 脱髓鞘现象在感染艾滋病毒的老年人中更为普遍，在那些感染艾滋病毒的老年人中更为普遍。 与正常衰老相关的 AUD 共病，可能导致运动和认知缺陷。同样，非 皮层下和小脑齿状核中的血红素铁沉积随着年龄的增长而增加，可能是其基础 步态和平衡障碍。平衡稳定性和认知能力是并行还是加速 有或没有 AUD 合并症且与常见脑标志物相关的 HIV 的衰老轨迹仍然存在 不清楚。在此，我们提出了一个纵向协议，使用一套神经影像方法来识别 我们假设局部组织退化的机制是姿势稳定性、步态、 以及对因艾滋病毒感染和澳元而衰老的男性和女性的认知。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，即表现出年龄与疾病的相互作用。 具体目标 1：使用 FLuid- 通过结构 MRI 检测白质高信号 (WMH) 体积 衰减反转恢复 (FLAIR) 成像将被量化并区分为脑室周围 (PVWMH) 或深部 (DWMH) 位于皮质叶、脑干和动脉区域。 具体目标 2：将通过定量测量髓鞘完整性和区域铁沉积 磁敏图 (QSM) 和扩散张量成像 (DTI)。非血红素铁将量化为 皮层下灰质结构（苍白球、尾状核、壳核、 红核、齿状核）。 QSM 抗磁负磁化率与 DTI 相结合将用于 表征白质束和 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。静态姿势稳定性将 使用平衡平台进行测量，产生摇摆路径长度、摇摆方向和躯干震颤的指标。步态 将在内部进行视频记录和测量，产生动态步态连贯性和稳定性的指标。 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 体积、局部铁沉积和髓磷脂破坏的影响将通过 我们对姿势稳定性和认知过程的静态和动态测量。