MOTOR FUNCTION AND COGNITIVE DECLINE IN AGING PRIMATES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 目前，运动功能减退和认知功能丧失之间的联系机制还知之甚少。为了帮助解决这个问题，我们正在用恒河猴(Macaca Mulatta)进行一系列实验，恒河猴和人类一样，在衰老过程中表现出认知能力的下降。此外，它可以在严格控制的环境条件下保持(例如，饮食、温度、光周期、药物和性类固醇暴露)。在这项正在进行的试点研究中，我们使用空间工作记忆的延迟反应测试、识别记忆的延迟非匹配样本测试和复杂反应时间来评估认知功能；我们还使用简单的反应时间任务来评估运动速度，通过食物提取任务来评估精细运动功能，通过对自发和动机运动的视频跟踪分析来评估运动功能，以及通过持续的家庭笼子监测来评估昼夜活动和睡眠质量指数。这些测量使我们能够检验与年龄相关的运动能力下降和昼夜节律紊乱与同时存在的与年龄相关的认知能力下降密切相关的假设。这项初步研究代表了一种快速且经济高效的方法，可以确定恒河猴是否可以作为未来机械学研究和治疗策略发展的实用动物模型。此外，这些数据将对我们在OHSU的临床合作者以及其他正在研究人类认知老化的研究人员有价值，他们正在规划相关人体研究的发展和实施。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Currently, the mechanisms linking motor decline and cognitive loss are poorly understood. To help overcome this problem, we are conducting a series of experiments using the rhesus monkey (Macaca mulatta), which like humans shows cognitive decline during aging. Moreover, it can be maintained under carefully controlled environmental conditions (e.g., diet, temperature, photoperiod, medication, and sex-steroid exposure). In this ongoing pilot study, we are assessing cognitive function using the delayed response test of spatial working memory, the delayed non-matching-to-sample test of recognition memory, and complex reaction time; we are also assessing motor speed with a simple reaction time task, fine motor function with food retrieval tasks, locomotor function with videotracking analysis of spontaneous and motivated locomotion, and circadian activity and sleep quality indices with continuous home cage monitoring. These measurements enable us to test the hypotheses that age-associated motor decline and circadian rhythm disruption are closely correlated with concurrent age-associated cognitive decline. This pilot study represents a rapid and cost-effective way of establishing whether the rhesus monkey can act as a pragmatic animal model for future mechanistic studies and for the development of treatment strategies. Moreover, the data will be valuable to our clinical collaborators at OHSU, who are planning the development and implementation of related human studies, and to other investigators who are studying human cognitive aging.