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

描述(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指标的敏感性和特异性，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)，并提高诊断的准确性水平。DMN涉及多个脑区，包括前扣带回皮质、后扣带回皮质、外顶叶、额叶中叶和海马旁区域。当一个人醒着但安静地休息时，DMN是活跃的；它是大脑中“意识流”处理的基础网络。在可能患有AD的患者中，FDG PET持续显示外侧颞叶皮质、后扣带回皮质、内嗅觉皮质和中颞叶结构的低代谢。因此，参与DMN和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老年人和可能患有AD的老年人。这种检测与DMN相关的大脑活动的方法为那些研究和治疗MCI和AD患者的人提供了一个新的工具，并可能导致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手段，并增加旨在缓解症状或治疗有效性的临床试验的可解释性。这项研究通过比较不同神经成像方法(定量FDG PET葡萄糖摄取率、fMRI DMN和(探索性)FDG PET DMN)的数据，进一步研究了最近的发现，以确定哪种方法可以最好地将受试者归入他们适当的诊断组(基于神经心理学评估定义的组)。另一个目标(探索性目标)是确定(通过路径分析)DMN内的哪些通路对神经退行性变过程最敏感。这些信息将有助于通过识别可能显示痴呆症最早迹象的大脑区域，为高危人群识别生物标记物，并集中治疗以稳定受影响区域的功能，从而有助于以上列出的好处。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组、MCI组和健康对照组。每个人都将接受诊断性质量的神经心理测试、APOE基因分型、fMRI和FGD PET扫描。这一特定于公共卫生领域的项目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中更早地识别高危患者，提供非侵入性可重复测试，评估治疗效果，并帮助进行鉴别诊断。阿尔茨海默氏症协会表示，如果不在早期和准确的诊断措施、治疗方法和治疗方面取得进展，推迟疾病的发生，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.