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.

项目摘要/摘要： 老年人和衰老的记忆投诉是阿尔茨海默氏病的主要危险因素 （AD），给人的印象是，逐渐失去记忆能力，最终在痴呆症中最终导致 成为变老几乎普遍的后果。我们的研究通过 研究80岁以上的年轻人，他们的记忆表现似乎已经逃脱了与年龄有关 下降，这仍然是50-60岁的年龄至少正常的范围，我们已经标记了 “超级代表”。我们招募了一个专门且独特的超级代表和控件，致力于 死亡时的纵向评估和大脑捐赠。我们的初步研究确定了域特异性生物学， 超级词的社会心理和遗传特征，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经济神经元和稀疏的皮质 与认知平均同龄人相比，阿尔茨海默氏症病理学。这些功能可能部分贡献 维持超过第8个生活的出色记忆表现。该项目计划扩展 通过假设驱动的功能性大脑的新评估来表征超老式表型 网络连通性，基因表达的区域分布以及树突状，突触和轴突的完整性 标记。拟议的项目将使我们能够扩展我们独特的超级代价和认知群体 平均同龄人和解决了与弹性和认知储备的神经生物学有关的重要问题。 通过识别有助于老年有卓越记忆表现的神经生物学特征，结果 该项目将有助于隔离因素，以促进成功的认知衰老，也许也可以防止年龄 相关的脑部疾病，例如AD。该项目依赖已经被部分招募的队列 它的纵向设计，多学科结构和对协作友好的组织增加了 将结果进步实现的可能性。