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

阿尔茨海默病（AD）的特征在于记忆和其他认知能力的进行性下降，最终影响日常功能。AD最早的行为表现之一包括非认知领域的表现不佳，例如观察到的运动功能减慢步态1。是否所有发展为AD的个体在认知表现之前经历步态减慢尚不清楚。代谢失调可能是AD 2的前兆和可能的早期标志物。我们假设AD前认知和运动双重下降的个体在AD诊断前表现出特定的代谢紊乱。 在巴尔的摩老龄化纵向研究（BLSA）中，我们计划使用定量代谢组学来检验中心假设，即在MCI/AD诊断之前认知和运动能力双重下降的个体表现出独特的代谢特征。代谢表型和生物标志物的初步结果支持代谢途径。鉴于BLSA的样本量限制和研究样本的高度选择性，我们的目标是使用健康，衰老和身体成分研究的数据来验证BLSA中获得的结果。我们假设，在BLSA中识别的代谢特征也将预测随后的双重下降。 主要目标是：1）在发展痴呆症之前使用认知和运动表现轨迹鉴定表型组，2）评估代谢组学谱与随后的双重衰退之间的预测关联，以及3）将鉴定的预测谱与BLSA中鉴定的那些进行比较。我们的长期目标是使用早期行为表型和新型生物标志物的组合来扩展对高危个体的早期识别。

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.