NEURAL SUBSTRATES OF AGE-RELATED COGNITIVE DECLINE IN MONKEYS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 恒河猴是人类正常衰老的模型，允许认知测试之后进行最佳的脑组织保存以供研究。该项目测试了以下假设：年龄相关的认知能力下降是由一系列轻度退行性变化引起的，这些变化始于白色物质中的炎症，然后是神经元中的功能变化和结构变化。这是一个纵向项目，跟踪一组12只中年雌性恒河猴，从13岁到15岁开始，为期5年。定期进行行为评估，以确定与年龄相关的认知能力下降的速度，并确定受试者之间的差异，以区分“成功”衰老的猴子和相对“不成功”衰老的猴子。定期进行MRI扫描，收集血液样本和CSF样本，以评估不同的衰老标志物。在五年结束时，脑组织样本将用于识别导致认知能力下降的变化。由于认知障碍的程度在13 - 15岁时是轻度的，但在18 - 20岁时是高的，这些数据将使我们能够确定与认知下降速度相关的大脑变化，目的是设计旨在减缓或逆转认知下降的治疗干预措施。

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. The rhesus monkey is a model of normal human aging that allows cognitive testing to be followed by optimal preservation of brain tissue for study. This projects tests the hypothesis that age-related cognitive decline results from a cascade of mild degenerative changes beginning with inflammation in white matter followed by functional and then structural changes in neurons. This is a longitudinal project that follows a group of 12 middle aged female rhesus monkeys for five years beginning between 13 and 15 years of age. Regular behavioral assessment is conducted to identify the rate of age-related cognitive decline and to determine how this differs among subjects in order to differentiate between monkeys that age "successfully" and those that are relatively "unsuccessful". Regular MRI scans, blood samples and CSF samples are collected to assess different markers of aging. At the end of five years the brain tissue samples will be used to identify changes responsible for cognitive decline. As the degree of cognitive impairment is mild at 13 - 15 but high by 18 - 20 years of age, these data will allow us to identify brain changes associated with the rate of cognitive decline with the goal of designing therapeutic interventions aimed at slowing or reversing cognitive decline.