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

项目摘要/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)的实地考察工作 会增加额外的血液生物标记物。我们已经得到资金在A/T/N中建立措施 框架--即ADRD病理生理学和神经退行性变所特有的淀粉样蛋白(A)和tau(T) NFL捕捉到的变化。这是很好的第一步，因为现在正在考虑A/T/N框架中的措施 是ADRD病理生理学特征的核心。在本补充资料中，我们请求提供额外的支持 这个框架之外的生物标记物已经成为与认知相关的越来越多的兴趣的焦点， 尤其是在临床环境之外的样本中。越来越多的证据表明，这些生物标志物可能是 即使在A/T/N框架的范围内也是相关的；例如，不是针对 大脑可能与A/T/N框架中的大脑特定标记物相互作用，以塑造ADRD结果。 我们建议增加(A)新的生物标记物，这些标记物可能是ADRD病理生理学特有的，但已经开发出来 只是最近和(B)与认知相关的生物标记物一直是人们日益感兴趣的焦点， 尤其是在社区环境中。为此，我们将整合现有的和新的生物标记，以反映(A) 血管、炎症和免疫损伤，以及(B)生物老化，以探讨它们的独立性 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。 具体地说，我们建议增加更多基于血液的生物标记物，包括Olink神经病学小组， 血红蛋白A1c，可能与血管疾病和淀粉样蛋白进展相关的炎性标志物- Tau级联、内皮功能标记物、血脑屏障问题标记物、血铅水平以及 生物老化措施[目标1]；记录新措施[目标2]；构建基于血液的生物标记物- 具体抽样重量[目标3]；以及传播新的测量、重量和文件[目标4]。全 拟议的补充活动将在最初的五年期R01预算期结束前完成。 拟议的补充活动将增加并保持项目的总体影响，使之符合 其最初批准的目的和目的。

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.