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异常值可能是一个信息的人群 发现抗性和弹性的行为，环境和/或生物学机制 进行广告和相关的痴呆症。该RADCO项目1的目标1-3，标题为“认知弹性” 和抵抗表型项目，是衡量认知弹性的3种不同的方法 在近500个百货认知超级老年人的样本中，有600个后代和 没有认知障碍，而120个配偶则没有父母的长寿。没有 认知障碍，尤其是在极端年龄的认知障碍，一百派认知超级名言是 定义，认知上有弹性。在没有与AD相关的神经病理学变化的情况下 他们将抵抗AD。项目1提案以下3个特定目标：特定目标1。 认知功能 - 神经成像相关性。一百季学的认知弹性 认知超级词，评估认知功能测量与结构之间的不一致 认知障碍和AD的功能性MRI相关性。特定目标2：认知 功能 - 生物标志物的广告相关风险。 RADCO样品中的仪表认知弹性 通过评估认知功能度量和纵向测定之间的不一致 AD，神经变性和神经炎症的生物标志物指数。特定目标3：认知 功能 - 神经病理学相关性。仪表认知和大脑的弹性以及对 通过评估认知能力的不一致，AD和其他神经病理学 功能测量和神经病理测量。这些目标的行为将有所不同 参与者根据弹性内表型。这些内型型以及 相关的生物样品资源（包括等离子体和脑组织）将通过 项目2研究人员发现了与之相关的受保护因素和机制 弹力。