The goal of this study is first to identify phenotypic groups using pre-clinical motor and memory declines, then to determine the specific metabolomic signature at a single assessment and changes over time that discriminates motor- and memory-dual decliners from other groups (usual agers, memory decliner only, gait decliners only) using a metabolomics platform, and finally to examine the association between changes in this specific metabolic signature and changes in neuroimaging markers of neurodegeneration and amyloid deposition. The four phenotypic groups motor decliners only, memory decliners only, and motor and memory dual decliners have been created. We found that, consistent with previous reports, the dual decliners had the highest risk for developing AD/MCI in the BLSA study. These results have been used as part of a meta-analysis where we show higher risk of AD/MCI in dual decliners in multiple cohorts. This manuscript has been submitted. The analysis examining the associations between the phenotypic groups with brain imaging data in BLSA is ongoing. The second goal of the project was to examine the plasma metabolomic profiles of each phenotypic group to gain insight into the mechanisms underlying the link between MCI/AD. Plasma samples are currently being processed for metabolomic assessment.
