This renewal application in response to the National Institute of Aging program announcement: AR-16-359 NIA ? Revision and Resubmission Program Project Applications proposes the addition of a new, one-year project to the Einstein Aging Study program project (NIH/NIA: P01 AG03949). Since 1993, the EAS has been a population based longitudinal study of older individuals residing in Bronx, New York. The program project has long focused on risk factors and cognitive changes that predict the subsequent onset of dementia, particularly Alzheimer?s disease (AD). The proposed work will expand the scope of EAS in a new direction by adding metabolite data related to the exposures of interest in the existing program project. The value of this work is that these new measures and/or a selected combination thereof may serve as early markers for the identification of high risk individuals, and elucidation of potential intervention targets for AD. This will be achieved by leveraging the EAS database and biorepository which contain detailed longitudinal assessments and serial bio-specimens from over 2,200 individuals who have been recruited and followed by the study. These resources will be used to conduct a nested case-control study of incident AD cases and closely matched, cognitively normal controls identified based on longitudinal EAS data. The proposed project will allow us to refine and target a panel of metabolites related to AD risk using an efficient study design and state of the art metabolomics approaches. The long-term goal is to extend this proposed work to examine the association of the identified metabolites with novel ambulatory indicators of cognitive change currently being collected in the EAS projects. The ongoing EAS has an overarching goal of improving the detection of early cognitive change by using advances in ambulatory cognitive assessments that reduce intra-individual variability and improve sensitivity for detecting change. The current projects are currently recruiting and following a new sample of 600 individuals who are completing novel ambulatory cognitive assessments annually. In keeping with this theme, the proposed new project will expand the science of the EAS in a new direction and will lay the foundation for assessing serum biomarkers in individuals who are currently completing annual ambulatory cognitive assessments to determine whether metabolites that predict incident AD may be used to identify individuals at risk for early cognitive decline prior to AD onset.
Metabolomics is an emerging field that shows great promise in identifying metabolites that are associated with preclinical abnormalities that predict the onset of subsequent clinical outcomes. The proposed work will expand the scope of the Einstein Aging Study program project (NIH/NIA: P01 AG03949) in new directions by adding metabolite data related to risk factors of cognitive aging and Alzheimer?s disease.
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