ELSA Exposome Enhancement Relevant to Alzheimer's Disease and AD-related Dementias

ELSA 暴露体增强与阿尔茨海默病和 AD 相关痴呆症相关

• 批准号: 10661220
• 负责人: Andrew Steptoe
• 金额: $ 173.28万
• 依托单位: UNIVERSITY COLLEGE LONDON
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-11 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10661220
• 关键词: Address; Adult; Aging; Alzheimer' s Disease; Alzheimer' s disease related dementia; Biological; Biological Markers; Birth; Blood; Blood specimen; Chemical Exposure; Child Development; Childhood; Cognition; Cognitive; Cohort Analysis; Data; Dementia; Development; Dimensions; Drug Targeting; Economic Factors; Environmental Exposure; Family; Funding; Future; Health; Health behavior; Impaired cognition; Individual; Life Cycle Stages; Life Experience; Longitudinal Studies; Measures; Modeling; Parents; Participant; Pathway interactions; Population Study; Proteins; Proteomics; Protocols documentation; Role; Sampling; Time; Trauma; Work; childhood adversity; cognitive testing; cohort; dementia risk; early life adversity; ethnic minority; experience; genome-wide; innovation; life history; member; migration; mild cognitive impairment; novel; prospective; psychosocial; racial and ethnic; recruit; residence; sociodemographic factors; tool

The English Longitudinal Study of Ageing (ELSA) is an important platform for population-based studies of Alzheimer’s Disease and Alzheimer’s Disease Related Dementias for several reasons. First, it has been in progress since 2002 with repeated measures of health, cognition, biomarkers, sociodemographic and economic factors, allowing for the long-term determinants of dementia to be analyzed. Second, the Harmonized Cognitive Assessment Protocol (HCAP) was administered in ELSA in 2018, and a second HCAP is planned for 2023, providing comprehensive data related to dementia and mild cognitive impairment that can be extrapolated to the complete cohort. Third, ELSA is closely modelled on HRS, facilitating detailed comparisons and replication. This application is for funds to enhance exposure measures relevant to AD/ADRD in two important dimensions identified in the NOSI that are central to the parent R01: biological innovation and enrichment of psychosocial measures. First, we plan to carry out proteomic profiling of the ELSA cohort using bloods collected in 2004 and 2008. The relationship between protein levels and cognitive decline and the development of dementia will, in conjunction with existing genome-wide assessments and existing biomarkers, provide a powerful tool for identifying novel pathways that could be of value as future drug targets. We will use the Olink proteomic platform that is being applied in a subsample of the HRS, as well as in the National Child Development Study (NCDS) 1958 birth cohort in the UK. The use of common tools will enable cross-cohort analysis in the future, and will support the replicability of findings. The second focus of this application is on the enhancement of the life history data in ELSA. The life history module was administered in 2007, and since then the sample has been refreshed several times. We therefore do not know about the experiences of around 44% of the current members of ELSA before they joined the study. We plan to offer a full life history assessment to these individuals, while adding some more detailed questions for those who previously completed the module. We will collect information about places of residence, work and earnings, partners and family, migration, health, and health behaviors through the life course, together with childhood living conditions and childhood adversity. Administration of the module to the new racial/ethnic minority sample being recruited in wave 10 (2021-2022) of ELSA will result in the first large-scale quantitative assessment of the life histories of these groups in the UK. The data will allow future analyses of issues such as cognitive stimulation during work, adult trauma, and early adversity in relation to AD/ADRD risk, while providing the platform for linkage with life course physical and chemical exposures. We will also address the issue of the validity of retrospective measures of life history by comparisons with the prospective data collected in the NCDS 1958 birth cohort, to obtain an accurate picture of the robustness of retrospective accounts of earlier life experiences.

英语衰老纵向研究（ELSA）是基于人群的研究的重要平台 阿尔茨海默氏病和阿尔茨海默氏病与痴呆有关的痴呆症的原因有多种。首先，它一直在 自2002年以来的进步，重复衡量健康，认知，生物标志物，社会人口统计学和 经济因素，可以分析痴呆症的长期决定者。第二， 2018年在ELSA中管理了统一认知评估方案（HCAP），第二个 HCAP计划于2023年，提供与痴呆和轻度认知障碍有关的全面数据 可以推断到完整的队列。第三，ELSA是在HRS上密切建模的，支持 详细的比较和复制。该应用程序是为了增强相关曝光措施的资金 在NOSI中确定的两个重要维度的AD/ADRD是父r01的核心： 生物创新和精神措施的丰富。首先，我们计划执行蛋白质组学 使用2004年和2008年收集的血液对ELSA队列的分析。蛋白质之间的关系 水平和认知能力下降以及痴呆症的发展将与现有的全基因组结合 评估和现有生物标志物为识别可能是的新型途径提供了强大的工具 价值作为未来的药物靶标。我们将使用正在应用于 HRS以及国家儿童发展研究（NCDS）1958年在英国的出生队列。使用 常见工具的元素将在将来实现跨核心分析，并将支持调查结果的复制性。 该应用程序的第二个重点是增强ELSA的生活历史数据。生活 历史模块是在2007年管理的，从那时起，样品已刷新了几次。我们 因此，在他们之前不了解大约44％的Elsa成员的经历 加入了研究。我们计划向这些人提供充实的生活历史评估，同时添加更多 对于那些以前完成该模块的人的详细问题。我们将收集有关地点的信息 通过居住，工作和收入，合作伙伴和家庭，移民，健康和健康行为 生活课程，以及童年的生活条件和童年广告。模块的管理 在ELSA的第10波（2021-2022）中招募的新种族/族裔少数民族样本将导致第一个 对这些群体在英国的生活史的大规模定量评估。数据将允许未来 分析工作期间认知刺激，成人创伤和早期广告等问题的分析 AD/ADRD风险，同时提供与生命过程的物理和化学暴露的平台。我们 还将通过比较与 NCDS 1958出生队列中收集的前瞻性数据，以获取准确的鲁棒性图片 回顾性的对早期生活经历的说法。