Neurometabolic profile of mild cognitive impairment using multiplexed edited MRS

使用多重编辑 MRS 分析轻度认知障碍的神经代谢特征

基本信息

批准号：
9759752
负责人：
Richard Anthony Edward Edden
金额：
$ 20.44万
依托单位：
JOHNS HOPKINS UNIVERSITY
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：
2018-08-15 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9759752
关键词：
Address Age Alzheimer&apos s Disease Amyloid beta-Protein Anaerobic Bacteria Anterior Antioxidants Aspartate Biological Markers Brain Brain imaging Brain region Chemicals Chemistry Clinical Cognition Cognitive Cognitive deficits Data Deposition Detection Development Disease Energy Metabolism Functional disorder Future Generations Glutamates Glutathione Image Impaired cognition Impairment Individual Interruption Lipids Longitudinal Studies Magnetic Resonance Spectroscopy Measurable Measurement Measures Medial Metabolic dysfunction Methodology Methods Mitochondria Modeling N-acetylaspartate N-acetylaspartylglutamate Neuraxis Neurobiology Neurofibrillary Tangles Neuromodulator Neurons Neurotransmitters Outcome Oxidation-Reduction Oxidative Stress Pathologic Patients Phase Play Positron-Emission Tomography Prevention Proteins Reactive Oxygen Species Resolution Risk Role Sampling Studies Severities Signal Transduction Site System Temporal Lobe Testing Tissues amyloid formation ascorbate brain tissue cohort design experimental study gamma-Aminobutyric Acid healthy aging in vivo interest mild cognitive impairment mitochondrial dysfunction neurobiological mechanism neurochemistry neuroimaging neuron loss neurotransmission normal aging oxidative damage pre-clinical radiotracer sex tau Proteins

项目摘要

Summary Mild Cognitive Impairment (MCI) is a preclinical form of Alzheimer's Disease (AD), characterized by cognitive deficits that are intermediate between those observed in healthy aging and AD. Amnestic multi-domain MCI (aMCI-MD) is a subtype of MCI with high (~40%) rates of conversion to AD, representing a valuable cohort for mechanistic studies of AD pathophysiology at a relatively early phase. The primary pathological/imaging finding in AD/MCI is of abnormal protein deposition in brain tissue, but the mechanisms by which this deposition is initiated and ultimately results in cognitive decline, are poorly understood. Recent developments in edited magnetic resonance spectroscopy (MRS) have substantially accelerated measurements of low- concentration metabolites of key interest in MCI, including redox compounds (glutathione and ascorbate), neurotransmitters and neuromodulators (GABA, glutamate, aspartate and N-acetylaspartylglutamate), and other compounds including the anaerobic product lactate. In this study, we will apply the new editing experiment HERCULES (Hadamard Editing Resolves Chemicals Using Linear Estimation of Spectra) to measure levels of these metabolites in three pathologically important brain regions (medial temporal lobe, anterior and posterior cingulate) in subjects with aMCI-MD and age- and sex-matched healthy controls. We will also test hypothesized relationships between neurochemistry and cognitive outcomes, and between MRS metabolite levels and prior PET imaging of amyloid-β and tau protein deposition.

概括轻度认知障碍（MCI）是阿尔茨海默氏病（AD）的临床前形式，其特征是认知在健康衰老和AD中观察到的缺乏症。羊膜多域MCI （AMCI-MD）是MCI的亚型，转换为AD的率很高（约40％），代表有价值的队列在相对较早的阶段，AD病理生理学的机理研究。主要的病理/成像在AD/MCI中的发现是脑组织中蛋白质异常的沉积，但是该机制的机制启动沉积，并最终导致认知能力下降，知之甚少。最近的发展在编辑的磁共振光谱（MRS）中，对低 - MCI关键兴趣的浓度代谢产物，包括氧化还原化合物（谷胱甘肽和抗坏血酸），神经递质和神经调节剂（GABA，谷氨酸，天冬氨酸和N-乙酰甲基谷氨酸），以及其他化合物在内，包括厌氧产物。在这项研究中，我们将应用新的编辑实验大力神（Hadamard编辑解决方案化学药品使用光谱的线性估计）来测量三种重要的病理学重要的这些代谢物的水平 AMCI-MD和年龄和年龄和年龄和年龄和性匹配的健康对照。我们还将测试神经化学与认知结果以及MRS代谢物水平与淀粉样蛋白和Tau蛋白的先前PET成像沉积。