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

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）和早期可能的阿尔茨海默病（AD），并提高诊断准确性水平。DMN涉及多个脑区，包括前扣带和后扣带皮层、外侧顶叶皮层、额叶中部和海马旁区。当一个人清醒但安静地休息时，DMN是活跃的；正是这个网络构成了大脑中“意识流”处理的基础。在可能患有AD的患者中，FDG PET一致显示外侧颞叶、后扣带皮层、内嗅皮层和颞叶中部结构的代谢低下。因此，参与DMN和受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，用功能磁共振成像评估DMN的完整性足以区分健康的老年人和可能患有阿尔茨海默病的老年人。这种检测与DMN相关的大脑活动的方法为研究和治疗MCI和AD患者提供了一种新的工具，并可能提高在早期阶段准确诊断MCI/AD的能力；提供一种评估状态变化的方法，并增加旨在缓解症状或治疗效果的临床试验的可解释性。本研究通过比较不同神经成像方法（定量FDG PET葡萄糖摄取比，fMRI DMN和（探索性）FDG PET DMN）的数据来进一步研究最近的发现，以确定哪种方法可以最好地将受试者划分到适当的诊断组（基于神经心理学评估定义的组）。额外的目标（探索性目的）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。这些信息将有助于确定可能出现最早痴呆症迹象的大脑区域，确定高危人群的生物标志物，并集中治疗以稳定受影响区域的功能，从而为上述列出的益处做出贡献。为了实现这些目标，我们将为每个诊断组招募20名年龄在60-85岁之间的人：可能的AD， MCI和健康对照组。每个人都将接受诊断质量的神经心理学测试、APOE基因分型、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，临床医生可以利用该工具在疾病过程的早期显著识别有风险的患者，提供无创可重复的测试，评估治疗效果，并帮助鉴别诊断过程。阿尔茨海默氏症协会指出，如果在早期和准确的诊断措施、治疗方法以及延迟疾病发作的治疗方面没有进展，痴呆症有可能成为本世纪最大的公共卫生问题。

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.