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

认知超级老化：探索对衰老和阿尔茨海默病的恢复力和抵抗力的模型

• 批准号: 10901316
• 负责人: CHANGIZ GEULA
• 金额: $ 74.79万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10901316
• 关键词: Cognitive; SuperAging; model; explore; resilience

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.

项目概要/摘要： 记忆问题在老年人中普遍存在，衰老是阿尔茨海默病的主要危险因素 (AD)，导致人们认为记忆能力逐渐丧失，最终导致痴呆，可能 这几乎是变老的普遍后果。我们的研究探索了另一种衰老轨迹 研究 80 岁以上的老年人，他们的情景记忆表现似乎与年龄无关 下降，并且至少保持在 50-60 岁人群的正常范围内，我们已将其标记为 “超级老年人”。我们招募了一群专门且独特的超级老年人和控制者，致力于 纵向评估和死亡时的大脑捐赠。我们的初步研究确定了特定领域的生物制剂， 超级老年人的心理社会和遗传特征，包括维持皮质完整性（尤其是在 前扣带回），大量的前扣带回 Von Economo 神经元和稀疏的皮质 阿尔茨海默病病理学与认知能力一般的同龄人进行比较。这些功能可能部分有助于 在生命的八个十年后保持卓越的记忆性能。该项目计划延长 通过假设驱动的大脑功能新颖评估来表征超级老化表型 网络连接、基因表达的区域分布以及树突、突触和轴突的完整性 标记。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 平均同龄人并解决与弹性和认知储备的神经生物学相关的重要问题。 通过识别有助于老年记忆表现的神经生物学特征，结果 该项目将有助于分离出促进成功认知老化的因素，或许还可以预防年龄增长 相关脑部疾病，例如AD。该项目依赖于已经部分招募的群体， 它的纵向设计、多学科结构和协作友好的组织增加了 取得相应进展的可能性。