Central Control and Neuroinflammatory Mechanisms of Locomotion in Older Adults with HIV

老年艾滋病毒感染者运动的中枢控制和神经炎症机制

• 批准号: 10618602
• 负责人: Roee Holtzer
• 金额: $ 86.2万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-12-01 至 2027-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10618602
• 关键词: Acceleration; Address; Adverse effects; Age; Aging; Attention; Attenuated; Biological Markers; Brain; Cognitive; Disease; Early Diagnosis; Elderly; Exhibits; Future; Gait; Gait abnormality; Gait speed; HIV; HIV/AIDS; Hemoglobin; Impaired cognition; Impairment; Inflammation; Inflammatory; Intervention; Learning; Locomotion; Magnetic Resonance Imaging; Measurement; Measures; Methods; Motivation; Outcome; Outcome Study; Pattern; Performance; Persons; Pharmacological Treatment; Prefrontal Cortex; Reporting; Reproducibility; Resources; Risk; Role; Structure; System; T-Lymphocyte Subsets; Training; Visit; Walking; Work; adverse outcome; antiretroviral therapy; brain magnetic resonance imaging; cognitive control; cognitive performance; comparison control; design; fall risk; falls; frontal lobe; functional near infrared spectroscopy; human old age (65+); improved; mind control; monocyte; multidisciplinary; neural; neuroinflammation; novel marker; remediation; walking speed

Mobility impairments including gait disorders and falls are debilitating and common, yet poorly understood in older persons with HIV (OPWH). The fronto-striatal circuitry is critical for brain control of locomotion and has been shown to be disrupted in HIV. Inflammation persists in HIV despite effective antiretroviral therapy and is a key driver of cognitive impairment among persons with HIV (PWH); the frontal cortex, which supports motivation and learning, is particularly vulnerable to the adverse effects of ongoing inflammation in the context of treated HIV, placing OPWH at risk for resulting mobility disorders. The role of brain circuits and neuroinflammation in gait and falls in OPWH has not been investigated to date, including whether walking performance under attention- demanding conditions could be durably improved with training, and thus amenable to remediation. We propose to use a validated dual-task walking paradigm (predictive of falls in older persons), a burst measurement (i.e., repeated trials) design, and functional-near-infrared spectroscopy (fNIRS) to determine the effect of HIV on brain activation levels and trajectories of walking in 120 OPWH (age ³ 50ys) and 120 controls without HIV. We will use multiple MRI methods to determine disruptions in the fronto-striatal circuitry and select markers of neuroinflammation to identify mechanisms of brain control of walking and risk of falls in OPWH. Brain activation patterns and learning trajectories of walking and improvements in their efficiency due to practice may be novel biomarkers to identify OPWH at risk of developing mobility impairments and falls as they survive into older age. Findings from this study will direct physical, cognitive, and pharmacological treatments to improve functional brain control of walking, which in turn will lead to interventions to reduce fall risk in OPWH.

包括步态障碍和福尔斯在内的行动障碍是使人衰弱的常见疾病，但在 老年艾滋病毒感染者组织。额-纹状体回路对大脑控制运动至关重要， 在艾滋病病毒中被破坏。尽管进行了有效的抗逆转录病毒治疗，HIV感染者的炎症仍然存在， 艾滋病毒感染者认知障碍的关键驱动因素（PWH）;支持动机的额叶皮层 和学习，特别容易受到持续炎症的不利影响，在治疗的背景下， 艾滋病毒，使OPWH面临由此导致的行动障碍的风险。脑回路和神经炎症在脑损伤中的作用 到目前为止，尚未对OPWH中的步态和福尔斯进行研究，包括是否在注意力集中的情况下行走， 通过培训可以持久地改善苛刻的条件，因此可以进行补救。我们提出 为了使用有效的双任务步行范例（预测老年人的福尔斯），爆发测量（即， 重复试验）设计和功能近红外光谱（fNIRS），以确定HIV对大脑的影响 120名OPWH（年龄≥ 50岁）和120名无HIV对照者的激活水平和行走轨迹。我们将 使用多种MRI方法来确定额纹状体回路的中断，并选择 神经炎症，以确定OPWH中大脑控制行走和福尔斯风险的机制。大脑激活 步行的模式和学习轨迹以及由于练习而提高其效率可能是新颖的 生物标志物，以确定OPWH在老年时有发生移动障碍和福尔斯的风险。 这项研究的结果将指导物理，认知和药物治疗，以改善功能 大脑控制行走，这反过来又会导致干预措施，以减少OPWH的跌倒风险。