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.

英国老龄化纵向研究（艾尔莎）是一个重要的平台，以人口为基础的研究， 阿尔茨海默病和阿尔茨海默病相关痴呆症有几个原因。首先，它已经在 自2002年以来，通过反复测量健康、认知、生物标志物、社会人口和 经济因素，允许对痴呆症的长期决定因素进行分析。二是 协调认知评估方案（HCAP）于2018年在艾尔莎进行，第二次 HCAP计划于2023年推出，提供与痴呆症和轻度认知障碍相关的全面数据 可以外推到整个队列。第三，艾尔莎是密切仿照HRS，促进 详细的比较和复制。此申请是为基金加强曝光措施有关 在NOSI中确定的两个重要方面对AD/ADRD的影响，这两个方面对母公司R 01至关重要： 生物创新和丰富心理社会措施。首先，我们计划进行蛋白质组学研究， 使用2004年和2008年收集的血液对艾尔莎队列进行分析。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 评估和现有的生物标志物，提供了一个强大的工具，用于确定新的途径， 作为未来的药物靶点。我们将使用Olink蛋白质组学平台，该平台正在应用于 HRS，以及英国国家儿童发育研究（NCDS）1958年出生队列。使用 共同工具的使用将使今后能够进行跨群组分析，并将支持研究结果的可复制性。 本申请的第二个重点是增强艾尔莎中的生命史数据。生命 2007年管理了历史模块，此后，样本已更新数次。我们 因此，他们不知道大约44%的艾尔莎现任成员的经历， 加入了研究。我们计划为这些人提供一个完整的生活史评估，同时增加一些 对以前完成该模块的人提出详细问题。我们将收集有关地点的信息 居住，工作和收入，伴侣和家庭，移民，健康和健康行为， 生命历程，以及童年生活条件和童年逆境。管理模块， 在艾尔莎的第10波（2021-2022年）中招募的新种族/少数民族样本将导致第一个 对英国这些群体的生活史进行大规模的定量评估。这些数据将使未来 分析问题，如工作中的认知刺激，成人创伤，以及与 AD/ADRD风险，同时提供与生命周期物理和化学接触联系的平台。我们 还将讨论的问题的有效性追溯措施的生活史的比较， 在NCDS 1958年出生队列中收集的前瞻性数据，以准确了解 对早期生活经历的回顾性描述。