Longitudinal Trajectories of Physical and Cognitive Function among Persons Aging with HIV

项目总结和摘要 老年艾滋病毒感染者（PWH）的认知障碍率很高， 与一般人群相比。这些功能状态的下降与以下因素有关： 威尔斯亲王医院的发病率及死亡率显著。在一般y人群中的老年人中， 已经确定了身体和认知功能之间的动态关系。在威尔斯亲王医院， 以前已经注意到认知受损和身体功能之间的联系，但纵向 认知和身体功能的轨迹以及它们之间的关系尚未得到评估。二甲双胍 有望成为衰老清除剂正在进行临床试验，以研究二甲双胍在预防 与年龄相关的下降在没有艾滋病毒的老年人中。本提案将调查纵向 PWH患者认知和身体功能之间的关系，并评估二甲双胍使用的潜在影响 在这些轨迹上。这项拟议的研究将利用三个大型前瞻性、观察性、 感染艾滋病毒或有感染艾滋病毒风险的男性和女性队列。此次调查将首次全面审视 在一大群PWH中认知和身体功能之间的纵向关联，并评估其影响 二甲双胍治疗对PWH患者这些结局的影响。我们的研究结果将告知重点和理想的时机， 干预措施，如二甲双胍用于预防认知和身体疾病的正式干预性临床试验， 老年威尔斯亲王医院的功能下降。此外，该提案符合GEMSSTAR计划的使命， 支持一名年轻的研究人员，寻求连接老化和艾滋病毒研究，以改善对老年威尔斯亲王医院的护理。

PROJECT SUMMARY AND ABSTRACT Older persons with HIV (PWH) experience high rates of cognitive impairment and accelerated declines in function compared to the general population. These functional status declines have been associated with significant morbidity and mortality in among PWH. Among the elderly in the general y population, longitudinal dynamic relationships between physical and cognitive function have been identified. In PWH, cross-sectional associations between impaired cognition and physical function have been previously noted, but longitudinal trajectories of cognitive and physical function and how they are related have not been evaluated. Metformin has shown promise as a senolytic agent. Clinical trials are underway to investigate use of metformin in preventing age-related declines in among elderly adults without HIV. This proposal will investigate the longitudinal relationship between cognitive and physical function in PWH and assess the potential impact of metformin use on these trajectories. The proposed study will utilize data available from three large prospective, observational cohorts of men and women with or at risk for HIV. This investigation will be the first to comprehensively examine longitudinal associations between cognitive and physical function in a large group of PWH and assess the impact of metformin therapy on these outcomes among PWH. Our findings will inform the focus and ideal timing of interventions such as a formal interventional clinical trial of metformin use to prevent cognitive and physical function declines among older PWH. Moreover, this proposal aligns with the GEMSSTAR program’s mission to support a young investigator seeking to bridge aging and HIV research to improve care for older PWH.