Educational and Early Life Predictors of Mild Cognitive Impairment: New Evidence about Mediators and Moderators from High School & Beyond

轻度认知障碍的教育和早期生活预测因素：关于高中调解者和调节者的新证据

• 批准号: 10745895
• 负责人: John Robert Warren
• 金额: $ 50.05万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10745895
• 关键词: Aging; Alzheimer' s disease related dementia; Amyloid; Amyloid beta-42; Award; Biological; Biological Aging; Biological Assay; Biological Markers; Blood; Blood - brain barrier anatomy; Blood Vessels; Blood brain barrier dysfunction; Blood specimen; Brain; Budgets; C-reactive protein; Chronic Disease; Clinical; Cognition; Cognitive; Cognitive aging; Communities; Consent; Consumption; DNA Methylation; Data; Dementia; Diabetes Mellitus; Documentation; Education; Endothelium; FGF2 gene; Fibrin fragment D; Fibrinogen; Fibroblast Growth Factor; Functional disorder; Funding; Glial Fibrillary Acidic Protein; Glycosylated hemoglobin A; Immune response; Immunologics; Inflammaging; Inflammation; Inflammatory; Injury; Knowledge; Lead levels; Life; Light; Measures; Mediator; Nerve Degeneration; Neurology; Outcome; PGF gene; Parents; Pathologic; Pathology; Persons; Physiological Processes; Population Heterogeneity; Prediabetes syndrome; Process; Research; Rest; Risk; Sampling; Shapes; Surveys; Threonine; Time; Urokinase Plasminogen Activator Receptor; Vascular Diseases; Vascular Endothelial Growth Factors; Weight; Whole Blood; blood lead; blood-based biomarker; community setting; cytokine; dementia risk; high school; immunosenescence; indexing; inflammatory marker; interest; member; mild cognitive impairment; neurofilament; novel marker; preservation; protein biomarkers; receptor for advanced glycation endproducts; response; specific biomarkers; tau Proteins; tau-1

PROJECT SUMMARY/ABSTRACT We propose a supplement to the award that supports the 2021 High School and Beyond (HSB) fieldwork that would add additional blood-based biomarkers. We are already funded to construct measures in the A/T/N framework—that is, amyloid (A) and tau (T) specific to ADRD pathophysiology as well as neurodegenerative (N) changes captured by NfL. This is a great first step since measures from the A/T/N framework are now considered central to the characterization of ADRD pathophysiology. In this supplement, we request additional support for biomarkers outside of this framework that have been the focus of increasing interest as relevant to cognition, especially in samples outside of clinical settings. There is growing evidence that these biomarkers may be relevant even within the context of the A/T/N framework; for example, inflammatory markers not specific to the brain may interact with brain-specific markers in the A/T/N framework to shape ADRD outcomes. We propose to add (a) newer biomarkers that may be specific to ADRD pathophysiology but that were developed only recently and (b) biomarkers that have been the focus of increasing interest as relevant to cognition, especially in community settings. In doing so, we will integrate established and novel biomarkers reflecting (a) vascular, inflammatory, and immunological injury and (b) biological aging in order to probe their independent impacts on cognitive outcomes and the degree to which they interact with A/T/N biomarkers. Specifically, we propose to add additional blood-based biomarkers including the Olink Neurology panel, hemoglobin A1c, inflammatory markers potentially related to vascular disease and progression of the amyloid- tau cascade, markers of endothelial function, markers of blood-brain barrier problems, blood lead levels, and measures of biological aging [Aim 1]; document the new measures [Aim 2]; construct blood-based biomarker- specific sampling weights [Aim 3]; and disseminate the new measures, weights, and documentation [Aim 4]. All proposed supplemental activities would be completed by the end of the original five-year R01 budget period. The proposed supplemental activities will increase and preserve the overall impact of the project consistent with its originally approved Aims and purposes.

项目总结/摘要 我们建议对该奖项进行补充，以支持2021年高中及以后（HSB）的实地考察， 会增加更多的血液生物标志物。我们已经获得资金在A/T/N中构建措施 框架-即ADRD病理生理学和神经退行性（N）特异性淀粉样蛋白（A）和tau（T） 由NFL捕获的变化。这是一个伟大的第一步，因为现在考虑了A/T/N框架的措施 ADRD病理生理学特征的核心。在本补充文件中，我们请求对以下内容提供额外支持： 在这个框架之外的生物标志物已经成为与认知相关的日益关注的焦点， 尤其是在临床环境之外的样品中。越来越多的证据表明，这些生物标志物可能是 甚至在A/T/N框架的背景下也是相关的;例如，非特异性的炎症标志物 大脑可能与A/T/N框架中的大脑特异性标记物相互作用，以形成ADRD结果。 我们建议添加（a）可能对ADRD病理生理学具有特异性但已开发的更新生物标志物 仅在最近和（B）作为与认知相关的生物标志物已经成为日益关注的焦点， 特别是在社区环境中。在这样做的过程中，我们将整合已建立的和新的生物标志物，反映（a） 血管、炎症和免疫损伤以及（B）生物老化，以探索它们的独立性。 对认知结果的影响以及它们与A/T/N生物标志物相互作用的程度。 具体来说，我们建议增加额外的血液生物标志物，包括Olink神经病学小组， 血红蛋白A1 c，可能与血管疾病和淀粉样蛋白进展相关的炎症标志物， tau级联、内皮功能标志物、血脑屏障问题标志物、血铅水平，以及 生物老化的措施[目标1];记录新措施[目标2];构建基于血液的生物标志物- 具体的抽样权重[目标3];以及传播新的衡量标准、权重和文件[目标4]。所有 拟议的补充活动将在最初的五年R 01预算期结束时完成。 拟议的补充活动将增加和保持项目的总体影响， 其最初批准的目标和宗旨。