Metabolomic Signatures Predicting Dual Cognitive and Gait Decline for the Health ABC Study

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Alzheimers disease (AD) is characterized by a progressive decline in memory and other cognitive abilities ultimately affecting daily function. One of the earliest behavioral manifestations of AD includes poor performance in non-cognitive domains, such as motor function observed as slowed gait1. Whether all individuals who develop AD experience slowed gait prior to cognitive manifestations is unknown. Metabolic dysregulation may be a precursor to and possible early marker of AD2. We hypothesize that individuals with cognitive- and motor-dual decline before AD exhibit specific metabolic disorders prior to AD diagnosis. In the Baltimore Longitudinal Study of Aging (BLSA), we plan to use quantitative metabolomics to test the central hypothesis that individuals with dual decline in cognitive and motor performance prior to MCI/AD diagnosis exhibit a unique metabolic profile. Preliminary results of metabolic phenotypes and biomarkers support a metabolic pathway. Given sample size limitations of BLSA and the highly selective nature of the study sample, we aim to validate findings obtained in the BLSA using data from the Health, Aging and Body Composition Study. We hypothesize that metabolic signatures identified in the BLSA would also predict subsequent dual decline. The main goals are: 1) identify phenotypic groups using cognitive and motor performance trajectories before developing dementia, 2) evaluate predictive associations between metabolomic profiles and subsequent dual decline and 3) compare identified predictive profiles with those identified in BLSA. Our long-term goal is to extend early identification of high-risk individuals using a combination of early behavioral phenotypes and novel biomarkers.