Motor Function and Cognitive Decline in Aging Primates

衰老灵长类动物的运动功能和认知衰退

• 批准号: 7357424
• 负责人: HENRYK F URBANSKI
• 金额: $ 16.94万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7357424
• 关键词: Address; Age; Age-associated memory impairment; Aging; Animal Model; Animals; Circadian Rhythms; Clinical; Cognitive; Cognitive aging; Complex; Condition; Controlled Environment; Data; Delayed Memory; Dementia; Development; Development Plans; Diagnostic; Diet; Disruption; Early Diagnosis; Elderly; Experimental Animal Model; Exposure to; Female; Food; Future; Gait; Gonadal Steroid Hormones; Home environment; Human; Impaired cognition; Individual; Intervention; Life Style; Link; Locomotion; Macaca mulatta; Measurable; Measures; Memory; Modeling; Monitor; Motor; Motor Skills; Pattern; Periodicity; Pharmaceutical Preparations; Photoperiod; Pilot Projects; Population; Primates; Reaction Time; Research; Research Personnel; Resources; Retrieval; Sampling; Selection Bias; Series; Short-Term Memory; Sleep; Sleep Fragmentations; Speed; Staging; Temperature; Testing; Therapeutic Intervention; Time; Training; age related; base; cognitive function; cohort; cost; human study; human subject; indexing; memory recognition; neurobiological mechanism; neuromechanism; nonhuman primate; opportunity cost; prognostic; research study; response; therapy development

DESCRIPTION (provided by applicant): Up to 50% of all individuals over age 85 have a measurable decline in cognitive function. Cognitive decline reliably predicts the imminent development of functional cognitive impairment, and therefore its early detection provides an opportunity for cost-effective proactive planning and therapeutic intervention. As the US population rapidly ages, the need for more accurate early diagnostic and prognostic measures becomes an increasingly compelling issue. Our clinical collaborators at OHSU have recently shown that it may be possible to predict functional cognitive impairment by monitoring changes in motor function as well as declining cognitive function. Indeed, they have found that simple motor measures provide one of the best predictors of progression to dementia. Currently, the mechanisms linking motor decline and cognitive loss are poorly understood, in part due to the lack of appropriate experimental animal models. To help overcome this problem, we propose to conduct a series of experiments using the rhesus monkey (Macaca mulatta). Like humans, this primate shows cognitive decline during aging and, equally important, it can be maintained under carefully controlled environmental conditions (e.g., diet, temperature, photoperiod, medication, and sex-steroid exposure). In the proposed pilot study, we will assess 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 will assess 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 measures will allow us to test the hypotheses that age-associated motor decline and circadian rhythm disruption are closely correlated with concurrent age-associated cognitive decline. Furthermore, experiments will be repeated several times across the two-year testing period to provide preliminary data on longitudinal changes and predictive relationships. The proposed 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 development of treatment strategies. Moreover, the data will be of immediate relevance and value to clinical collaborators at OHSU, who are planning the development and implementation of related human studies, as well as others studying human cognitive aging.

描述（由申请人提供）：在所有85岁以上的个体中，高达50%的人有可测量的认知功能下降。认知能力下降可靠地预测了功能性认知障碍的即将发展，因此它的早期发现为具有成本效益的主动计划和治疗干预提供了机会。随着美国人口迅速老龄化，对更准确的早期诊断和预后措施的需求成为一个日益紧迫的问题。我们在OHSU的临床合作者最近表明，通过监测运动功能的变化和认知功能的下降，有可能预测功能性认知障碍。事实上，他们发现简单的运动测量提供了痴呆症进展的最佳预测指标之一。目前，运动能力下降和认知能力丧失之间的联系机制尚不清楚，部分原因是缺乏适当的实验动物模型。为了解决这个问题，我们建议用恒河猴（Macaca mulatta）进行一系列的实验。像人类一样，这种灵长类动物在衰老过程中表现出认知能力下降，同样重要的是，它可以在精心控制的环境条件下维持（例如，饮食、温度、光周期、药物和性类固醇暴露）。在初步研究中，我们将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；我们将通过简单的反应时间任务来评估运动速度，通过食物检索任务来评估精细运动功能，通过自发运动和动机运动的视频跟踪分析来评估运动功能，以及通过连续的家庭笼监测来评估昼夜节律活动和睡眠质量指标。这些措施将使我们能够测试与年龄相关的运动能力下降和昼夜节律紊乱与同时与年龄相关的认知能力下降密切相关的假设。此外，实验将在两年的测试期间重复多次，以提供关于纵向变化和预测关系的初步数据。拟议的试点研究代表了一种快速和经济有效的方法，可以确定恒河猴是否可以作为未来机制研究和治疗策略开发的实用动物模型。此外，这些数据将对OHSU的临床合作者具有直接的相关性和价值，他们正在计划开发和实施相关的人类研究，以及其他研究人类认知衰老的人。