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 认知完好的百岁老人作为极端的异常值，很可能是一个信息丰富的队列 发现抗性和复原力的行为、环境和/或生物机制 阿尔茨海默病和相关痴呆症。RADCO项目1的目标1-3，即认知复原力 和阻力表型项目，是测量认知韧性的三种不同方法 在近500名百岁认知超级老年人的样本中，600名患有和 无认知障碍，配偶对照120例，无父母长寿。没有 认知障碍，特别是在他们的极端年龄，百岁认知超级老年人是 定义，认知能力强。在没有与AD相关的神经病理变化的情况下， 他们会对AD产生抵抗力。项目1提出了以下3个具体目标：具体目标1。 认知功能--神经影像相关性。测量百岁老人的认知韧性 认知超级者，评估认知功能测量和结构之间的不一致性 功能磁共振成像与认知损害和阿尔茨海默病相关。具体目标2：认知 功能-AD相关的生物标志物风险。在RADCO样本中测量认知弹性 通过评估认知功能测量与纵向测试之间的不一致性 AD、神经退行性变和神经炎症的生物标志物指标。具体目标3：认知 功能与神经病理的相关性。测量认知和大脑的弹性和抵抗力 通过评估认知功能的不一致性来评估脑供者的AD和其他神经病理 功能测量和神经病理测量。这些目标的实现将有所不同 受试者根据弹性内表型。这些内表型以及 相关的生物样本资源，包括血浆和脑组织，将被传递给 项目2调查人员发现与以下方面有关的保护因素和机制 恢复力。