Cognitive SuperAging: A model to explore resilience and resistance to aging and Alzheimers disease

项目摘要/摘要： 记忆障碍在老年人中很普遍，衰老是阿尔茨海默病的主要危险因素 (AD)，导致记忆能力的逐渐丧失，最终导致痴呆症，可能 几乎是变老的普遍后果。我们的研究通过以下方式探索另一种老龄化轨迹 研究80岁以上的人，他们的情节记忆表现似乎没有与年龄相关 下降，这保持在至少对50-60岁的人来说是正常的范围内，我们已经标记 《超级老人》。我们招募了一群专门的和独特的超级老年人和控制者，致力于 死亡时的纵向评估和脑捐赠。我们的初步研究确定了特定领域的生物学， 超级老年人的心理、社会和遗传特征，包括维持皮质完整性(特别是在 前扣带回)、丰富的前扣带Von Economo神经元和稀疏的皮质 阿尔茨海默病与他们认知水平平均的同龄人进行比较。这些功能可能在一定程度上有助于 在超过第八个十年的寿命中保持卓越的内存性能。本项目计划延长 通过假说驱动的新的脑功能评估来表征超老表型 网络连通性、基因表达的区域分布以及树突、突触和轴突的完整性 记号笔。拟议的项目将使我们能够扩大我们独特的超级老年人群体，并在认知上 并解决与恢复力和认知储备的神经生物学相关的重要问题。 通过确定有助于老年人卓越记忆表现的神经生物学特征，结果 该项目将有助于分离促进认知成功老化的因素，或许还能防止衰老-- 相关的脑部疾病，如阿尔茨海默病。该项目对已经部分招募的队列的依赖， 其纵向设计、多学科结构和协作友好型组织增加了 取得相应进展的可能性。

PROJECT SUMMARY/ABSTRACT: Memory complaints are widespread among the elderly and aging is a major risk factor for Alzheimer's disease (AD), leading to the impression that a gradual loss of memory ability, eventually culminating in dementia, may be a nearly universal consequence of getting old. Our studies explore an alternative aging trajectory by studying 80+ year olds, who have episodic memory performance that appears to have escaped age-related decline and that remains in the range that is at least normal for 50-60 year-olds and we have labelled `SuperAgers'. We enrolled a dedicated and unique cohort of SuperAgers and Controls committed to longitudinal assessment and brain donation at death. Our initial studies identified domain-specific biologic, psychosocial, and genetic features of the SuperAgers, including maintenance of cortical integrity (especially in the anterior cingulate), an abundance of anterior cingulate Von Economo neurons and sparse cortical Alzheimer pathology compared to their cognitively average peers. These features may contribute in part to maintenance of superior memory performance past the 8th decade of life. This Project plans to extend the characterization of the SuperAging phenotype through hypothesis-driven novel evaluations of functional brain network connectivity, regional distribution of gene expression, and integrity of dendritic, synaptic and axonal markers. The proposed project will allow us to expand our unique group of SuperAgers and cognitively average peers and address important questions related to the neurobiology of resilience and cognitive reserve. By identifying neurobiologic features that contribute to superior memory performance in old age, outcomes from this project will help isolate factors that promote successful cognitive aging and perhaps also prevent age- related brain diseases such as AD. The project's reliance on a cohort that has already been partially recruited, its longitudinal design, multidisciplinary structure, and collaboration-friendly organization increases the likelihood that consequential progress will be achieved.