FMRI, PET and the Default Mode Network Classify MCI and AD

FMRI、PET 和默认模式网络分类 MCI 和 AD

• 批准号: 7480237
• 负责人: Michal Assaf
• 金额: $ 7.23万
• 依托单位: HARTFORD HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7480237
• 关键词: Affect; Age; Alzheimer' s Disease; Alzheimer' s Disease Pathway; Anterior; Apolipoprotein E; Area; Biological Markers; Biological Neural Networks; Brain; Brain region; Cerebrum; Clinical Trials; Conscious; Data; Data Analyses; Data Quality; Dementia; Diagnosis; Diagnostic; Differential Diagnosis; Disease; Eating; Elderly; Evaluation; Food; Functional Magnetic Resonance Imaging; Genotype; Glucose; Goals; Hour; Image; Impaired cognition; Injection of therapeutic agent; Lateral; Lead; Logistics; Magnetic Resonance Imaging; Measures; Medial; Metabolic; Methods; Modality; Nerve Degeneration; Neuropsychological Tests; Neurosciences Research; Onset of illness; Outcome; Parietal; Parietal Lobe; Pathway interactions; Patients; Personal Satisfaction; Persons; Pilot Projects; Positron-Emission Tomography; Prefrontal Cortex; Procedures; Process; Protocols documentation; Public Health; Purpose; Radioactive; Rate; Recruitment Activity; Regression Analysis; Relative (related person); Research; Rest; Risk; Scanning; Sensitivity and Specificity; Somatosensory Cortex; Staging; Standards of Weights and Measures; Stream; Structure; Symptoms; Techniques; Temporal Lobe; Testing; Therapeutic; Treatment Effectiveness; Treatment Efficacy; awake; base; cingulate cortex; diagnostic accuracy; drinking; entorhinal cortex; frontal lobe; glucose uptake; improved; independent component analysis; interest; mild neurocognitive impairment; neuroimaging; neurophysiology; neuropsychological; statistics; tool

DESCRIPTION (provided by applicant): The purpose of this two year study is to assess the sensitivity and specificity of newer neurophysiological measures, specifically the integrity of the default mode neural network (DMN), to identify amnestic mild cognitive impairment (MCI) and early probable Alzheimer's Disease (AD) and to improve diagnostic accuracy levels. The DMN involves several brain regions, including the anterior and posterior cingulate cortices, lateral parietal cortex, middle frontal lobe, and parahippocampal regions. The DMN is active when a person is awake but resting quietly; it is the network that underlies "stream of consciousness" processing in the brain. In patients with probable AD, FDG PET consistently reveals hypometabolism in lateral temporal cortex, posterior cingulate cortex, entorhinal cortex, and middle temporal lobe structures. Thus there is great overlap in the brain structures involved in the DMN and affected by AD. Recent neuroscience research has shown that evaluation of the integrity of the DMN with fMRI is sufficient to distinguish healthy elderly from those who have probable AD. This method of examining brain activity associated with the DMN provides a new tool for those who study and treat MCI and AD patients and may lead to improving the ability to accurately diagnose MCI/AD in the earliest stages; providing a means of assessing change in status, and increasing interpretability of clinical trials aimed at symptom relief or treatment efficacy. This study furthers the recent findings by comparing data from different neuroimaing methods (quantitative FDG PET glucose uptake ratios, fMRI DMN, and (exploratory) FDG PET DMN) to determine which approach can best classify subjects into their proper diagnostic group (groups defined based on neuropsychological assessment). The additional goal (exploratory aim) is to identify (via path analysis) which pathways within the DMN are most sensitive to the neurodegenerative process. This information will contribute to the benefits listed above by identifying brain regions that may show the earliest signs of dementia, identifying a biomarker for at-risk people, and focusing treatments to stabilize function in the affected regions. To accomplish these goals, we will recruit 20 people ages 60-85 for each of our diagnostic groups: probable AD, MCI, and healthy control. Each will receive diagnostic-quality neuropsychological testing, APOE genotyping, and an fMRI and a FGD PET scan. The important outcome of this project that is specific to the field of public health is the establishment of a tool with which clinicians can identify at risk patients significantly earlier in the disease process, provide noninvasive repeatable testing, evaluate treatment effectiveness, and aid in the process of differential diagnosis. Without advances in early and accurate diagnostic measures, therapeutic treatments, and treatments that delay the onset of the disease, the Alzheimer's Association states that dementia has the potential to become the largest public health problem of this century.

描述（由申请人提供）：这项为期两年的研究的目的是评估新的神经生理学测量的敏感性和特异性，特别是默认模式神经网络（DMN）的完整性，以识别遗忘性轻度认知障碍（MCI）和早期认知障碍可能的阿尔茨海默氏病 (AD) 并提高诊断准确性水平。 DMN 涉及多个大脑区域，包括前扣带皮层和后扣带皮层、外侧顶叶皮层、中额叶和海马旁区域。当一个人清醒但安静休息时，DMN 处于活跃状态；它是大脑中“意识流”处理的基础网络。在疑似 AD 患者中，FDG PET 始终显示外侧颞叶皮层、后扣带皮层、内嗅皮层和中颞叶结构代谢低下。因此，参与 DMN 并受 AD 影响的大脑结构有很大的重叠。最近的神经科学研究表明，通过功能磁共振成像评估 DMN 的完整性足以区分健康老年人和可能患有 AD 的老年人。这种检查与 DMN 相关的大脑活动的方法为研究和治疗 MCI 和 AD 患者提供了一种新工具，并可能提高早期准确诊断 MCI/AD 的能力；提供一种评估状态变化的方法，并提高旨在缓解症状或治疗效果的临床试验的可解释性。这项研究通过比较来自不同神经影像方法（定量 FDG PET 葡萄糖摄取比、fMRI DMN 和（探索性）FDG PET DMN）的数据，进一步确定了哪种方法可以最好地将受试者分类到适当的诊断组（根据神经心理学评估）。额外的目标（探索性目标）是确定（通过路径分析）DMN 内的哪些路径对神经退行性过程最敏感。这些信息将通过识别可能显示痴呆症最早迹象的大脑区域、识别高危人群的生物标志物以及重点治疗以稳定受影响区域的功能，从而有助于实现上述益处。为了实现这些目标，我们将为每个诊断组招募 20 名 60-85 岁的人：疑似 AD、MCI 和健康对照。每个人都将接受诊断质量的神经心理学测试、APOE 基因分型以及功能磁共振成像和 FGD PET 扫描。该项目针对公共卫生领域的重要成果是建立了一种工具，临床医生可以使用该工具在疾病过程中更早地识别高危患者，提供无创可重复检测，评估治疗效果并在此过程中提供帮助的鉴别诊断。阿尔茨海默氏症协会指出，如果早期准确的诊断措施、治疗方法和延迟疾病发作的治疗方法不取得进展，痴呆症有可能成为本世纪最大的公共卫生问题。