Administrative Supplement to Cognitive Resilience among Older Samoans

项目总结 这项拟议的行政补充以收集新的生物标志物可能会增加科学 从我们目前由NIA资助的R01中获得的与认知韧性相关的知识，标题为 年长的萨摩亚人的复原力。本增刊是基于最近出乎意料的事态发展而撰写的。 当我们提交亲本R01：(1)时，发现一种与较长端粒相关的基因变体 长度(28372734卢比)在萨摩亚人中出现的频率是任何其他人口的两倍多 研究；以及(2)我们发现我们父母格兰特的遗传预测因子，太平洋岛民特有的基因变体 CREBRF(Rs373863828)预测在我们的父代R01样本中感觉到的压力较小。因为更长的端粒长度 较低的压力与认知韧性有关，评估端粒长度基因变异和 应激生物标志物将使我们能够确定这些因素是否参与了 萨摩亚老年人的认知能力较强。代表两条途径的两个应激生物标志物 减少压力有益于大脑健康的途径是：(1)减少慢性炎症，如 C反应蛋白水平；以及(2)更好的T细胞功能，如较低的EB病毒抗体水平所表明的。 因此，利用强大的基础设施和600名萨摩亚老年人的登记样本，我们 在我们的父母R01中跟踪了3年多，我们的增刊的具体目标是第一次检查 是否：(1)端粒长度基因变异预测认知韧性；(2)较低的炎症(如上所述 通过较低的C反应蛋白水平)调节父母R01‘S预测因子’(CREBRF变异体和萨摩亚阳性年龄 信念)与认知韧性的联系；以及(3)适应性T细胞功能(如较低的EBV所示 抗体水平)调节亲本R01‘S预测因子与认知韧性之间的关联。 这项拟议的补编涉及2022年应对阿尔茨海默氏症国家计划的目标 疾病3指出，因为没有已知的干预措施可以肯定地预防、治疗或治愈 ADRD，有必要确定“ADRD的遗传基础”和“免疫和 炎症“，这可能会受到压力的影响。此外，通过研究美国年长的萨摩亚人的这些因素 和独立萨摩亚，我们将为国家情报机构增加认知复原力研究的目标作出贡献 在美国的种族和少数民族以及低收入和中等收入国家的个人中。 通过关注年长的萨摩亚人，这是一个具有独特遗传和文化素质的群体， 补充剂可能确定一条新的认知韧性的生物因果路径，这可能会导致未来 旨在造福萨摩亚社区和所有老年人的干预措施。

PROJECT SUMMARY This proposed administrative supplement to collect new biomarkers could increase the scientific knowledge related to cognitive resilience gained from our current NIA-funded R01 entitled, “Cognitive Resilience among Older Samoans.” This supplement builds on recent developments that were unforeseen when we submitted the parent R01: (1) it was discovered that a genetic variant associated with longer telomere length (rs28372734) appears more than twice as frequently among Samoans than any other population studied; and (2) we found that our parent grant’s genetic predictor, the Pacific-Islander-specific gene variant CREBRF (rs373863828) predicts lower perceived stress in our parent R01 sample. As longer telomere length and lower stress are associated with cognitive resilience, assessing the telomere-length gene variant and stress biomarkers will allow us to determine whether these factors contribute to the mechanism by which Samoan older individuals achieve cognitive resilience. The 2 stress biomarkers that represent 2 pathways through which lower stress can benefit brain health are: (1) lower chronic inflammation, as indicated by lower CRP levels; and (2) better T-cell functioning, as indicated by lower Epstein Bar Virus (EBV) antibody levels. Thus, leveraging the strong infrastructure and enrolled sample of 600 older Samoan persons that we are following over 3 years in our parent R01, our supplement’s specific aims are to examine for the first time whether: (1) the telomere-length gene variant predicts cognitive resilience; (2) lower inflammation (as indicated by lower CRP levels) mediates the parent R01’s predictors’ (the CREBRF variant and Samoan positive age beliefs) association with cognitive resilience; and (3) adaptive T-cell function (as indicated by lower EBV antibody levels) mediates the association of the parent R01’s predictors with cognitive resilience. This proposed supplement addresses the goals of the 2022 National Plan to Address Alzheimer’s Disease3 which points out that because there are no interventions known to definitely prevent, treat or cure ADRD, there is a need to identify “the genetic underpinning of ADRD” and “the role of immunity and inflammation,” which can be impacted by stress. Further, by studying these factors in older Samoans in the US and Independent Samoa, we would contribute to NIA’s goals of increasing the study of cognitive resilience among racial and ethnic minorities in the US as well as individuals in low- and middle-income countries. By focusing on older Samoans, a group which has unique genetic and cultural qualities, this supplement could identify a new biological causal pathway to cognitive resilience that is likely to lead to future interventions for benefitting the Samoan community as well as all older persons.