Brain structure, chemistry and function investigations in aging using MRI/MRS

使用 MRI/MRS 研究衰老过程中的脑结构、化学和功能

• 批准号: 8736676
• 负责人: Josephine Egan
• 金额: $ 52.37万
• 依托单位: NATIONAL INSTITUTE ON AGING
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8736676
• 关键词: Affective; Age; Aging; Agonist; Alcohol consumption; Alcoholism; Alzheimer' s Disease; Amyloid deposition; Anterior; Area; Atrophic; Baltimore; Behavior; Biological Markers; Brain; Brain Mapping; CNR1 gene; Cephalic; Chemistry; Clinical Research; Cognition; Cognitive; Corpus Callosum; Data; Dementia; Demyelinations; Disease; Disease Progression; Endocannabinoids; Enrollment; European; Financial compensation; Food; Functional Magnetic Resonance Imaging; Future; Glucose; Glutamates; Glutamine; Glycolysis; Goals; Hippocampus (Brain); Human; Hypothalamic structure; Image; Individual; Insula of Reil; Insulin; Insulin Resistance; Investigation; Journals; Knowledge; Longitudinal Studies; MRI Scans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Manuscripts; Marchiafava Bignami disease; Measurement; Measures; Medial; Mental disorders; Metabolic; Metabolism; Metric; Necrosis; Nerve Degeneration; Neurotransmitters; Participant; Pathogenesis; Patients; Performance; Peripheral; Personality; Personality Traits; Pharmaceutical Preparations; Play; Positron-Emission Tomography; Prefrontal Cortex; Preparation; Process; Publications; Publishing; Reporting; Research; Resolution; Rest; Role; Staging; Structure; Techniques; Temporal Lobe; Toxic effect; Ventral Tegmental Area; age group; aging brain; base; brain metabolism; cardiovascular risk factor; data reduction; dietary control; disease diagnosis; exenatide; gamma-Aminobutyric Acid; glucose metabolism; in vivo; independent component analysis; insulin secretion; interest; memory encoding; memory retrieval; mild cognitive impairment; morphometry; neurochemistry; neuroimaging; novel; psychologic; response; sex; tau Proteins; trait; uptake; visual stimulus

Volumetric measures obtained with analysis of high-definition 3D structural MRI images capture neuroanatomical variability which may be associated with long-standing traits or may help explain why certain brain areas or individuals are vulnerable to neurodegenerative processes. Volumetric measures can also demonstrate in vivo toxicity resulting from certain behaviors, such as alcohol consumption. This last year, we performed voxel based morphometry analyses on structural MRI scans to explore the neuroanatomical variability associated with long-standing personality traits, which may explain why certain individuals are vulnerable to psychiatric disease, dementia or show inefficient psychological response mechanisms. We discovered neuroanatomical differences related to the Five Factors of Personality (published in the journal "Human Brain Mapping"). Moreover, we performed a voxel based morphometry analysis in Baltimore Longitudinal Study of Aging (BLSA) participants and detected a significant volumetric decrease in the premotor portion of the frontal corpus callosum associated with alcohol consumption, controlling for dietary, demographic and cardiovascular risk factors (published in the journal "European Neuropsychopharmacology"). This finding suggests an increased vulnerability of this region, which may help explain why this same region develops demyelination and necrosis in alcoholism (Marchiafava-Bignami disease). In addition, we studied how a data reduction technique called group-level independent component analysis (ICA) may be applied to structural MRI images and generate measures for clusters of different brain areas (Independent Components). We applied ICA to MRI data collected in the ADNI study and examined how they can discriminate between participants with normal cognition, mild cognitive impairment (MCI) and Alzheimer's disease (AD). We showed that ICs can be useful as classifiers and predictors of future AD diagnosis or conversion to AD from MCI (the manuscript is currently under review). In addition, given the association between insulin resistance and Alzheimer's disease, we examined how volumetric and FDG-PET uptake measures for several key regions of interest for AD relate to peripheral insulin resistance. We found that insulin resistance promotes two abnormal and pathogenic compensations: it increases glucose metabolism in the hippocampus and medial temporal lobe at the stage of mild cognitive impairment and increases glucose metabolism in default mode network nodes at the stage of AD (the manuscript is currently under preparation for publication). Prior fMRI studies suggest that these compensatory increases in metabolism are associated with disease progression. Currently, we are performing two fMRI studies, one on cephalic insulin secretion and the other on food apetitiveness, as part of a broader study on the effects of endocannabinoid (CB1) receptor drugs on metabolism. The goal of the first study is to demonstrate a rise in insulin levels in response to food visual stimuli (cephalic insulin response) as a result of activation of certain brain areas (insula, anterior cingulate, hypothalamus, ventral tegmental area, etc). Moreover, given the presence of CB1 receptors in the candidate areas, we aim to demonstrate a difference in their level of activation with CB1 agonists and antagonists. The goal of the second study is to demonstrate dissociable effects of CB1 receptor stimulation on food value (food choices) and salience (intensity of such choices).

通过分析高清3D结构MRI图像获得的体积测量可以捕获神经解剖学的变异，这可能与长期存在的特征有关，也可能有助于解释为什么某些大脑区域或个体容易受到神经退行性过程的影响。体积测量也可以证明由某些行为（如饮酒）引起的体内毒性。去年，我们对结构MRI扫描进行了基于体素的形态分析，以探索与长期人格特征相关的神经解剖学变异性，这可能解释了为什么某些人容易患精神疾病、痴呆或表现出低效的心理反应机制。我们发现了与人格五要素相关的神经解剖学差异（发表在《人脑图谱》杂志上）。此外，我们对巴尔的摩衰老纵向研究（BLSA）参与者进行了基于体素的形态测量分析，发现与饮酒相关的额叶胼胝体运动前部分的体积显著减少，控制了饮食、人口统计学和心血管风险因素（发表在《欧洲神经精神药理学》杂志上）。这一发现表明该区域的易损性增加，这可能有助于解释为什么酒精中毒时该区域出现脱髓鞘和坏死（marchiafawa - bignami病）。此外，我们研究了如何将一种称为群体水平独立成分分析（ICA）的数据简化技术应用于结构MRI图像，并生成不同脑区簇的测量方法（独立成分）。我们将ICA应用于ADNI研究中收集的MRI数据，并检查它们如何区分正常认知，轻度认知障碍（MCI）和阿尔茨海默病（AD）的参与者。我们发现，ic可以作为分类器和预测器，用于未来AD诊断或从MCI转化为AD（该手稿目前正在审查中）。此外，鉴于胰岛素抵抗与阿尔茨海默病之间的关联，我们研究了AD的几个关键区域的体积和FDG-PET摄取测量与外周胰岛素抵抗的关系。我们发现胰岛素抵抗促进了两种异常和致病性代偿：轻度认知障碍阶段海马和内侧颞叶葡萄糖代谢增加，AD阶段默认模式网络节点葡萄糖代谢增加（论文目前正在准备发表中）。先前的功能磁共振成像研究表明，这些代偿性代谢增加与疾病进展有关。