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: 10359727
• 负责人: CHANGIZ GEULA
• 金额: $ 75.18万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10359727
• 关键词: Address; Age; Age-associated memory impairment; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Anterior; Axon; Biological; Biometry; Brain; Brain Diseases; Cessation of life; Characteristics; Chronology; Cognition; Cognitive; Cognitive aging; Collaborations; Consequentialism; Data; Dementia; Dendritic Spines; Elderly; Enrollment; Episodic memory; Evaluation; Funding; Gene Expression; Genetic; Genetic Polymorphism; Immune; Immunohistochemistry; Individual; Inflammation; Label; Lateral; Life; MAP2K3 gene; Magnetic Resonance Imaging; Maintenance; Measures; Memory; Memory Loss; Modeling; Molecular; Nerve Degeneration; Neurobiology; Neurocognitive; Neurofibrillary Tangles; Neuronal Plasticity; Neurons; Neuropsychology; Neurosciences; Outcome; Parietal Lobe; Participant; Pathway Analysis; Pattern; Performance; Phenotype; Physiological; Positron-Emission Tomography; Process; Proteins; Reporting; Research; Research Priority; Resistance; Rest; Risk Factors; Structure; Synapses; Thinness; Time; Tissues; United States National Institutes of Health; Universities; age related; aging brain; base; behavioral neurology; cingulate cortex; cognitive neuroscience; cognitive performance; cognitive reserve; cohort; demographics; density; design; entorhinal cortex; gene network; graph theory; human old age (65+); impression; in vivo; insight; longitudinal design; multidisciplinary; neocortical; neuroimaging; neuropathology; normal aging; novel; peer; prevent; protective factors; psychosocial; recruit; resilience; resistance mechanism; segregation; transcriptome; transcriptome sequencing; transcriptomics; white matter

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.

项目总结/摘要： 老年人中普遍存在记忆投诉，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的逐渐丧失，最终导致痴呆症， 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岁以上的奥尔兹，他们的情景记忆表现似乎已经摆脱了年龄相关的影响， 下降，并保持在范围内，至少是正常的50-60岁的人，我们已经标记 “超级烈火”。我们招募了一批专门的、独特的超级老年人和对照组，他们致力于 纵向评估和死亡时的大脑捐赠。我们最初的研究确定了特定领域的生物， 社会心理和遗传特征，包括维持皮质完整性（特别是在 前扣带回），丰富的前扣带回Von Economo神经元和稀疏的皮质 与认知能力一般的同龄人相比，老年痴呆症的病理学。这些特征可能部分有助于 在使用寿命的第八个十年后仍保持上级存储器性能。本项目计划将 通过假设驱动的脑功能新评价表征超级衰老表型 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， 平均同龄人和解决有关的重要问题，恢复力和认知储备的神经生物学。 通过识别有助于老年人上级记忆表现的神经生物学特征， 从这个项目将有助于隔离因素，促进成功的认知老化，也许也防止年龄- 相关的脑疾病，如AD。该项目对已经部分招募的队列的依赖， 它的纵向设计，多学科结构和合作友好的组织增加了 取得相应进展的可能性。