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

描述(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AD患者中普遍存在，并可在AD的早期阶段被检测到。这一公认的发现为我们提供了一个独特的机会来检查早期退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，而且与神经认知变量混淆。我们的长期目标是了解AD早期发生的嗅觉缺陷，并开发可靠的诊断工具，用于早期发现、监测和了解AD的功能病理过程。这项研究是为了响应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的形态数据将按照ADNI标准化方案获取。这一设计将允许通过该项目获得的神经认知、生物学(血液和尿液)和脑形态数据被添加到ADNI总体队列中。作为ADNI的辅助，我们将确定初级嗅觉皮质、内嗅觉和海马区的局部萎缩如何与相同结构中的嗅觉fMRI激活有关，以及这些测量与AD的心理物理和临床表现如何相关。本项目中开发的神经功能成像方法学可用于ADNI框架内的更广泛研究。这个项目是由两个假设驱动的：1)嗅觉功能磁共振可以识别早期AD的嗅觉缺陷；2)初级嗅皮层(POC)和内嗅觉/海马区的嗅觉fMRI激活与MCI和AD这些区域的萎缩程度相关。目的1：建立、验证和标准化嗅觉fMRI数据采集方法，以及相应的POC、内嗅皮层和海马区数据分析方法。目的：研究青年和老年正常对照组(NC)嗅觉fMRI信号特征及其与嗅觉阈值和嗅觉浓度的关系，以及轻度认知损害(MCI)和早期AD患者嗅觉fMRI激活和嗅觉浓度的变化。目的3：识别和量化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.