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

阿尔茨海默病（AD）的特点是记忆力和其他认知能力逐渐下降，最终影响日常功能。阿尔茨海默病最早的行为表现之一包括在非认知领域表现不佳，如运动功能表现迟缓。是否所有患有AD的个体在认知症状出现之前都会经历步态减慢尚不清楚。代谢失调可能是AD2的前兆和可能的早期标志。我们假设，在阿尔茨海默病诊断之前，认知和运动双重功能下降的个体表现出特定的代谢紊乱。

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.