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/文摘: