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

包括步态障碍和跌倒在内的活动障碍是令人衰弱和常见的，但对 老年艾滋病毒携带者(OPWH)。额纹状体回路是大脑控制运动的关键， 已被证明在艾滋病毒中受到干扰。尽管进行了有效的抗逆转录病毒治疗，但艾滋病毒仍存在炎症，这是一种 艾滋病毒携带者认知障碍的关键驱动因素；支持动机的额叶皮质 在接受治疗的情况下，尤其容易受到持续炎症的不利影响 HIV，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，还没有对OPWH的步态和跌倒进行调查，包括是否在注意力集中的情况下行走- 苛刻的条件可以通过培训得到持久的改善，因此可以进行补救。我们建议 为了使用有效的双任务行走范例(预测老年人跌倒)，突发测量(即， 重复试验)设计和功能-近红外光谱(FNIRS)来确定艾滋病毒对大脑的影响 120名OPWH患者(年龄50岁)和120名未感染HIV的对照组的步行活动水平和轨迹。我们会 使用多种MRI方法来确定额纹状体回路的中断，并选择 神经炎症以确定大脑控制行走的机制和OPWH跌倒的风险。脑激活 步行的模式和学习轨迹以及由于练习而提高的效率可能是新的 生物标记物，用于识别OPWH在存活到老年时出现行动能力障碍和跌倒的风险。 这项研究的发现将指导物理、认知和药物治疗以改善功能 大脑控制行走，这反过来将导致干预措施，以降低OPWH的跌倒风险。

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.