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

描述（由申请人提供）：我们将使用功能性MRI（fMRI）和定量体积MRI（vMRI）研究早期AD的嗅觉缺陷。嗅觉缺陷在AD患者中普遍存在，并且可以在AD的早期阶段检测到。这一明确的发现为我们提供了一个独特的机会来研究早期退行性变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，并与神经认知变量混淆。我们的长期目标是了解早期AD中发生的嗅觉缺陷，并开发可靠的诊断工具，用于早期检测，监测和了解AD的功能病理过程。本研究的设计是为了响应NIH PA-04-158，AD神经影像学倡议（ADNI）的辅助研究。受试者将按照ADNI的相同标准进行招募和筛选。将按照ADNI标准化方案采集vMRI的形态学数据。该设计将允许将本项目获得的神经认知、生物学（血液和尿液）和脑形态学数据添加到ADNI整体队列中。辅助ADNI，我们将确定如何在初级嗅觉皮层，内嗅和海马的局部萎缩涉及到嗅觉功能磁共振成像激活在相同的结构，以及如何这些套测量与AD的心理物理和临床表现。本项目中开发的神经功能成像方法可用于ADNI框架内更广泛的研究。该项目由两个假设驱动：1）早期AD的嗅觉缺陷可以通过嗅觉fMRI识别; 2）初级嗅觉皮层（POC）和内嗅/海马区域的嗅觉fMRI激活与MCI和AD中这些区域的萎缩程度相关。目标1：开发、验证和规范嗅觉功能磁共振成像数据采集方法，以及POC、内嗅皮层和海马的相应数据分析方法。目标二：研究正常青年人和老年人嗅觉功能磁共振成像（fMRI）信号及其与气味阈值和气味浓度的关系，以及轻度认知障碍（MCI）和早期AD患者fMRI激活和气味浓度感知的变化。目的3：确定和量化萎缩和嗅觉功能障碍之间的关系，在早期退化的网站。

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.