Administrative Supplement to Cognitive Resilience among Older Samoans

老年萨摩亚人认知弹性的行政补充

• 批准号: 10773593
• 负责人: BECCA R LEVY
• 金额: $ 35.44万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-03-01 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10773593
• 关键词: Address; Administrative Supplement; Age; Alzheimer' s Disease; Alzheimer' s disease related dementia; American Samoa; Antibodies; Award; Belief; Biological; Biological Markers; Blood; C-reactive protein; California; Cell physiology; Chronic; Cognition; Cognitive; Communities; Development; Diabetes Mellitus; Dryness; Elderly; Enrollment; Fingers; Funding; Future; Genetic; Glycosylated hemoglobin A; Goals; Grant; Health; Immunity; Incidence; Individual; Inflammation; Infrastructure; Intervention; Interview; Interviewer; Knowledge; Length; Measures; Mediating; Methods; Mission; National Institute on Aging; Pacific Islander; Parents; Participant; Pathway interactions; Persons; Population; Population Study; Qualifying; Research; Role; Saliva; Samoa; Samoan; Sampling; Site; Spottings; Stress; T-Lymphocyte; Time; Trans-Omics for Precision Medicine; Tropical Climate; United States National Institutes of Health; Variant; Virus; Visit; aged; brain health; cognitive benefits; cognitive performance; cohort; cost effective; ethnic minority; follow up assessment; follow-up; genetic predictors; genetic variant; improved; insight; low and middle-income countries; novel; parent grant; perceived stress; pharmacologic; prevent; protective allele; racial minority; resilience; risk variant; screening; telomere; user-friendly

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.

项目概要 拟议的收集新生物标志物的行政补充可以增加科学性 从我们当前 NIA 资助的 R01 中获得的与认知弹性相关的知识，题为“认知 老萨摩亚人的韧性。”本补充建立在最近不可预见的发展的基础上 当我们提交亲本 R01 时：（1）发现与较长端粒相关的遗传变异 length (rs28372734) 在萨摩亚人中出现的频率是其他人群的两倍多 研究过； （2）我们发现我们的父母资助的遗传预测因子，即太平洋岛民特有的基因变体 CREBRF (rs373863828) 预测我们的父 R01 样本中感知压力较低。由于端粒长度更长 较低的压力与认知弹性相关，评估端粒长度基因变异和 压力生物标志物将使我们能够确定这些因素是否有助于这种机制 萨摩亚老年人实现了认知弹性。代表 2 条途径的 2 个压力生物标志物 较低的压力可以通过以下方式有益于大脑健康：（1）降低慢性炎症，如较低的压力所示 CRP水平； (2) 更好的 T 细胞功能，如较低的 Epstein Bar 病毒 (EBV) 抗体水平所示。 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 在我们的母体 R01 中跟踪超过 3 年，我们的补充品的具体目标是首次检查 是否：（1）端粒长度基因变异预测认知弹性； (2) 降低炎症（如所示 通过较低的 CRP 水平）介导亲本 R01 的预测因子”（CREBRF 变异和萨摩亚阳性年龄 信念）与认知弹性的关联； (3) 适应性 T 细胞功能（如较低 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。 该拟议补充方案旨在实现 2022 年国家阿尔茨海默病计划的目标 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“免疫和免疫系统的作用” 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，我们将为 NIA 加强认知弹性研究的目标做出贡献 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。 通过关注老年萨摩亚人这一具有独特遗传和文化品质的群体， 补充剂可以确定一种新的认知弹性生物因果途径，这可能会导致未来 使萨摩亚社区以及所有老年人受益的干预措施。