Neuroimaging Study on Function-Structure Relationship of Olfactory Deficit in AD

描述（由申请人提供）：我们将使用功能磁共振成像（fMRI）和定量体积磁共振成像（vMRI）研究早期AD的嗅觉缺陷。嗅觉缺陷在阿尔茨海默病患者中很普遍，并且可以在阿尔茨海默病的早期阶段检测到。这一成熟的发现为我们提供了一个独特的机会来检查早期变性部位的病理变化与相关功能缺陷之间的直接关系。研究这种关系一直很困难，而且与神经认知变量相混淆。我们的长期目标是了解阿尔茨海默病早期发生的嗅觉缺陷，并开发可靠的诊断工具，以便早期发现、监测和了解阿尔茨海默病的功能病理过程。该研究是根据NIH PA-04-158， AD神经成像倡议（ADNI）的辅助研究而设计的。受试者将按照ADNI的相同标准进行招募和筛选。vMRI的形态学数据将根据ADNI标准化协议获得。该设计将允许该项目获得的神经认知、生物学（血液和尿液）和脑形态学数据被添加到ADNI总体队列中。辅助ADNI，我们将确定初级嗅觉皮层，内嗅和海马的局部萎缩如何与相同结构的嗅觉fMRI激活相关，以及这些测量值如何与AD的心理物理和临床表现相关。本项目开发的神经功能成像方法可用于ADNI框架内更广泛的研究。该项目基于两个假设：1)嗅觉功能mri可以识别早期AD患者的嗅觉缺陷；2) MCI和AD患者初级嗅皮质（POC）和内嗅/海马区的嗅觉fMRI激活与这些区域的萎缩程度相关。目标1：开发、验证和标准化嗅觉fMRI数据采集方法，以及相应的POC、内嗅皮质和海马数据分析方法。目的2：表征年轻和老年正常对照（NC）嗅觉fMRI信号及其与气味阈值和浓度的关系，以及轻度认知障碍（MCI）和早期AD受试者fMRI激活和气味浓度感知的变化。目的3：确定和量化在早期变性部位的萎缩和嗅觉功能障碍之间的关系。

DESCRIPTION (provided by applicant): We will study olfactory deficits in early AD using functional MRI (fMRI) and quantitative volumetric MRI (vMRI). Olfactory deficits are prevalent in AD patients and can be detected in the early stages of AD. This well established finding provides a unique opportunity for us to examine the direct relationship between pathological changes in the site of early degeneration and the associated functional deficit. Studying such a relationship has been difficult and confounded with neurocognitive variables. Our long-term objective is to understand the olfactory deficits occurring in the early AD and develop reliable diagnostic tools for the early detection, monitoring and understanding the functional-pathological processes of AD. The study is designed in response to NIH PA-04-158, Ancillary Studies to the AD Neuroimaging Initiative (ADNI). The subjects will be recruited and screened with the same criteria of ADNI. The morphological data for vMRI will be acquired following ADNI standardized protocols. This design will allow the neurocognitive, biological (blood and urine) and brain morphological data acquired by this project to be added into the ADNI overall cohort. Ancillary to ADNI, we will determine how the local atrophy in the primary olfactory cortex, entorhinal and hippocampus relates to the olfactory fMRI activation in the same structures and how these sets of measurement relate to the AD psychophysical and clinical expressions. The developed neurofunctional imaging methodology in this project may be utilized for a broader study within the framework of ADNI. This project is driven by two hypotheses: 1) the olfactory deficits in early AD can be identified by olfactory fMRI; 2) olfactory fMRI activation in the primary olfactory cortex (POC) and entorhinal/hippocampal regions correlates with the degree of atrophy in these regions in MCI and AD. Aim 1: Develop, validate and standardize olfactory fMRI data acquisition methods, and the corresponding data analysis methods on the POC, entorhinal cortex and hippocampus. Aim 2: Characterize olfactory fMRI signal and its relationships with odor threshold and concentration in young and old normal controls (NC), and the changes in fMRI activation and perception of odor concentration in mild cognitive impairment (MCI) and early AD subjects. Aim 3: Identify and quantify the relationship between atrophy and olfactory dysfunction at the sites of early degeneration.