Administrative Supplement to Cognitive Resilience among Older Samoans

项目摘要 这项收集新生物标志物的拟议行政补充措施可以增加科学研究， 从我们目前由美国国家情报局资助的R01中获得的认知弹性相关知识， 老年萨摩亚人的复原力"。本补编是根据最近未预见的事态发展编写的 当我们提交亲本R01时：（1）发现与较长端粒相关的遗传变异 长度（rs28372734）在萨摩亚人中出现的频率是任何其他人口的两倍多 研究;（2）我们发现，我们的父母格兰特的遗传预测，太平洋岛民特异性基因变异， CREBRF（rs373863828）预测在我们的亲本R01样品中较低的感知压力。随着端粒长度的增加 和较低的压力与认知弹性有关，评估端粒长度基因变异， 压力生物标志物将使我们能够确定这些因素是否有助于 萨摩亚老年人实现认知复原力。代表2种途径的2种应激生物标志物 通过降低压力可以有益于大脑健康的原因是：（1）降低慢性炎症，如降低 CRP水平;和（2）更好的T细胞功能，如较低的EB病毒（EBV）抗体水平所示。 因此，利用强大的基础设施和登记的600名萨摩亚老年人样本， 在我们的父R01中跟踪了3年以上，我们补充的具体目标是首次检查 是否：（1）端粒长度基因变体预测认知弹性;（2）较低的炎症（如所示 较低的CRP水平）介导父母R01的预测因子（CREBRF变异体和萨摩亚阳性年龄 （3）适应性T细胞功能（如较低的EBV所示） 抗体水平）介导亲本R01的预测因子与认知弹性的关联。 这一拟议的补充解决了2022年国家计划解决阿尔茨海默病的目标 疾病3指出，由于没有已知的干预措施可以明确预防，治疗或治愈 ADRD，有必要确定"ADRD的遗传基础"和"免疫的作用， 炎症，“这可能会受到压力的影响。此外，通过研究美国老年萨摩亚人的这些因素， 和独立萨摩亚，我们将有助于NIA的目标，增加认知弹性的研究 在美国的少数种族和族裔以及低收入和中等收入国家的个人中。 通过把重点放在老年萨摩亚人这个具有独特遗传和文化素质的群体上， 补充剂可以确定一个新的生物因果途径，认知弹性，这可能导致未来的 采取干预措施，使萨摩亚社区和所有老年人受益。

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.