Resilience and Resistance Phenotypes

恢复力和抗性表型

• 批准号: 10689332
• 负责人: SUSAN Y BOOKHEIMER
• 金额: $ 39.39万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-30 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10689332
• 关键词: Adult; Age; Aging; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid beta-42; Apolipoprotein E; Attenuated; Behavioral; Bilateral; Biological; Biological Assay; Biological Markers; Blood flow; Brain; Brain imaging; Brain region; Centenarian; Characteristics; Child; Clinical; Cognitive; Dementia; Exposure to; Functional Magnetic Resonance Imaging; Hippocampus; Hour; Human Resources; Image; Imaging Techniques; Impaired cognition; Individual; Liquid substance; Longevity; Magnetic Resonance Imaging; Magnetism; Maps; Measures; Medial; Myelin; Nerve Degeneration; Neuropsychology; Outcome; Parietal Lobe; Participant; Pathologic; Phenotype; Plasma; Positron-Emission Tomography; Predisposition; Recovery; Research Personnel; Resistance; Resolution; Resources; Rest; Risk Factors; Sampling; Spouses; Testing; Thick; White Matter Hyperintensity; arterial spin labeling; brain tissue; cognitive function; cohort; cytokine; endophenotype; high risk; indexing; mild cognitive impairment; neuroimaging; neuroinflammation; neuropathology; offspring; preservation; protective factors; resilience; resistance mechanism; tau aggregation; tau-1; therapeutic candidate; transcriptomics; white matter

Project 1 Summary Cognitively intact centenarians as extreme outliers are likely to be an informative cohort for discovering behavioral, environmental, and/or biological mechanisms of resistance and resilience to AD and related dementias. Aims 1-3 of this RADCO Project 1 titled, The Cognitive Resilience and Resistance Phenotypes Project, are 3 different approaches to gauging cognitive resilience amongst a sample of almost 500 centenarian cognitive super agers, 600 offspring with and without cognitive impairment, and 120 spouse controls without parental longevity. With no cognitive impairment, particularly at their extreme age, centenarian cognitive superagers are by definition, cognitively resilient. In the absence of neuropathologic changes associated with AD, they would be resistant to AD. Project 1 proposes the following 3 specific aims: Specific Aim 1. Cognitive Function-Neuroimaging Correlation. Gauge cognitive resilience in centenarian cognitive superagers, assessing discordance between cognitive function measures and structural and functional MRI correlates of cognitive impairment and AD. Specific Aim 2: Cognitive Function–Biomarker Risk of AD Correlation. Gauge cognitive resilience in the RADCO sample by assessing discordance between cognitive function measures and longitudinally assayed biomarker indices of AD, neurodegeneration and neuroinflammation. Specific Aim 3: Cognitive Function-Neuropathology Correlation. Gauge cognitive and brain resilience and resistance to AD and other neuropathologies in brain donors by assessing discordance between cognitive function measures and neuropathological measures. The conduct of these aims will differentiate participants according to resilience endophenotypes. These endophenotypes along with associated biosample resources including plasma and brain tissues will be passed on for use by Project 2 investigators for the discovery of protective factors and mechanisms associated with resilience.

项目1摘要 认知完整的百岁老人作为极端离群值可能是一个信息队列， 发现抵抗力和恢复力的行为，环境和/或生物机制 AD和相关痴呆症。本RADCO项目1的目标1-3，名为“认知弹性” 和抗性表型项目，是衡量认知弹性的三种不同方法 在近500名百岁老人的认知超级老人样本中， 没有认知障碍，120名配偶控制没有父母长寿。没有 认知障碍，特别是在他们的极端年龄，百岁认知超级老人是由 定义为认知弹性。在不存在与AD相关的神经病理学变化的情况下， 他们就能抵抗AD项目1提出了以下三个具体目标：具体目标1。 认知功能-神经影像学相关性。测量百岁老人的认知弹性 认知超级老人，评估认知功能测量和结构之间的不一致性， 以及认知障碍和AD的功能性MRI相关性。具体目标2：认知 AD相关性的功能-生物标志物风险。在RADCO样本中测量认知弹性 通过评估认知功能测量和纵向分析之间的不一致性， AD、神经变性和神经炎症的生物标志物指数。具体目标3：认知 功能-神经病理学相关性。测量认知和大脑的弹性和抵抗力， 通过评估脑捐赠者的认知和认知功能之间的不一致性， 功能测量和神经病理测量。这些目标的实施将区分 参与者根据弹性内表型。这些内表型沿着 包括血浆和脑组织在内的相关生物样本资源将被传递给 项目2研究人员为发现保护因素和机制相关的 resilience.