Multi-omic Investigation of Exercise Effects in Mild Cognitive Impairment

运动对轻度认知障碍的影响的多组学研究

基本信息

批准号：
9888296
负责人：
MARK MAPSTONE
金额：
$ 46.42万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-07-01 至 2022-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9888296
关键词：
Aerobic Aerobic Exercise Alzheimer disease prevention Alzheimer&apos s Disease Alzheimer&apos s disease pathology Alzheimer&apos s disease therapy Alzheimer’s disease biomarker Amyloid Biochemical Pathway Biological Assay Blood Blood Vessels Blood flow Blood specimen Brain Cerebrospinal Fluid Clinical Clinical Trials Cognition Cognitive Control Groups Data Data Set Dementia Development Disease Disease Pathway Disease Progression Elderly Energy Metabolism Enrollment Equilibrium Exercise Family Funding Future Genes Goals Health Healthcare Image Impaired cognition Individual Inflammation Intervention Investigation Laboratories Lipids Magnetic Resonance Imaging Mass Spectrum Analysis Measures Metabolic Metabolic Pathway Methods Modeling Modernization Molecular Profiling Monitor Outcome Outcome Measure Oxidative Stress Participant Pathogenesis Pathologic Pathway interactions Performance Phase Phenotype Phospholipids Pilot Projects Plasma Population Prevention program Proteins Proteomics Protocols documentation Public Health Publishing Randomized Research Personnel Resources Risk Sampling Scientist Site Societies Stretching Supervision Testing Training Transcript Validation age related amino acid metabolism aminoacid biosynthesis amnestic mild cognitive impairment arm base brain health cerebral atrophy cost cost effective data integration design economic cost experience experimental study functional outcomes functional status gene product insight metabolomics mild cognitive impairment minimally invasive model development multiple omics novel peripheral blood phase III trial pre-clinical primary outcome prodromal Alzheimer&apos s disease sedentary tau Proteins tau-1 treatment as usual treatment effect treatment program usual care arm

项目摘要

Alzheimer's disease (AD) is the most common age-related dementia, and is rapidly becoming a major public health problem. At present, there are no cures or disease-modifying therapies for AD. Without options to cure or even delay the onset of AD, the economic costs, healthcare burden, and impact on afflicted individuals, their families, and society will be devastating. The overall goal of this project is to examine the effect of aerobic exercise on central metabolic pathways using metabolomic and proteomic markers. We will leverage blood samples from 350 older adults with MCI enrolled in the funded ADCS-funded EXERT study. In this study, the two primary outcome measures will be quantitative levels of 24 metabolites and 21 proteins from previously published panels. The main independent measure will be exercise condition (aerobic exercise, stretching, sedentary) in the EXERT study. For the primary analyses, this will be a repeated measures, within-and- between subjects design examining exercise group effects on the metabolomic and proteomic measures. In a model development arm, we will integrate the metabolomic and proteomic measures in a putatively richer and more specific multi-omic model which may be more sensitive to exercise effects than the already established individual panels. Using the multi-omic and individual panels, we will also attempt to predict exercise effects for individual participants from baseline data. We will examine change in the metabolomic, proteomic, and multi- omic measures for other EXERT outcomes including CSF measures of amyloid and tau, brain atrophy from imaging, and other blood measures. Finally, in an exploratory analysis, we will perform untargeted metabolomic quantification of ~4700 metabolites to determine if more specific metabolomic panels may be identified. Our team is comprised of experienced basic and clinical scientists, clinical trialists, and biostatisticians with the resources to carry out this project. The results of this trial will elucidate metabolic mechanisms of exercise as a treatment and possibly prevention of Alzheimer's disease. The multi-omic panel and metabolomic panel from the untargeted metabolomics may provide new avenues for detecting Alzheimer's disease and for monitoring treatment effects in future clinical trials.

阿尔茨海默病 (AD) 是最常见的与年龄相关的痴呆症，并且正在迅速成为主要的公众疾病健康问题。目前，AD 尚无治愈方法或疾病缓解疗法。没有治愈的选择甚至延缓 AD 的发作、经济成本、医疗负担以及对受影响个人的影响、他们的家庭、社会都将受到毁灭性的打击。该项目的总体目标是检查有氧运动的效果使用代谢组学和蛋白质组学标记对中央代谢途径进行锻炼。我们将利用血液样本取自参加由 ADCS 资助的 EXERT 研究的 350 名患有 MCI 的老年人。在这项研究中，两个主要结果指标是先前研究的 24 种代谢物和 21 种蛋白质的定量水平发布的面板。主要的独立衡量标准是运动条件（有氧运动、伸展运动、 EXERT 研究中的久坐不动）。对于初步分析，这将是重复测量，并且- 受试者之间的设计检查运动组对代谢组学和蛋白质组学测量的影响。在一个模型开发部门，我们将把代谢组学和蛋白质组学测量整合到一个更丰富和更广泛的模型中。更具体的多组学模型，可能比已经建立的模型对运动效果更敏感单独的面板。使用多组学和个体小组，我们还将尝试预测运动效果来自基线数据的个体参与者。我们将研究代谢组学、蛋白质组学和多方面的变化其他 EXERT 结果的组学测量，包括脑脊液中淀粉样蛋白和 tau 蛋白的测量、脑萎缩成像和其他血液测量。最后，在探索性分析中，我们将进行无针对性的对约 4700 种代谢物进行代谢组学定量，以确定是否可以进行更具体的代谢组学组合确定。我们的团队由经验丰富的基础和临床科学家、临床试验人员和拥有开展该项目资源的生物统计学家。该试验的结果将阐明代谢运动作为治疗和可能预防阿尔茨海默病的机制。多组学小组来自非靶向代谢组学的代谢组学组合可能为检测阿尔茨海默病提供新途径疾病并用于监测未来临床试验中的治疗效果。