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

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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.