MCI嗅觉障碍中枢机制及其向AD转化的fMRI研究

Early detection of Alzheimer's disease (AD) is crucial for the prognosis improving. Now the biomarker for early diagnosis is hot issue in AD research. Mild cognition impairment (MCI) is high risk population of AD. Olfactory deficits have been observed in early stages of MCI, and the olfactory circuit can be investigated by task-fMRI. The mechanisms underlying MCI and AD olfactory deficits remain to be clarified and its predictive value in progression from MCI to AD need to be determined. In our previous study, it has been found that the gray matter volume decreased in hippocampus and orbit frontal cortex, which is involved in olfactory circuit. We hypothesized that MCI and AD may have functional impairments of olfactory circuits. In this study, the olfactory threshold, identification and discrimination of MCI and AD were evaluated; the structural and functional alterations of MCI and AD were studied by using structure-MRI and task-fMRI. The present study aims to investigate the pathophysiological mechanism of olfactory deficits in MCI and AD, and provide potential biomarkers for early detection of AD.

阿尔茨海默病(AD)的早期诊断有利于改善患者的预后，AD的早期诊断标记物是目前研究的热点。轻度认知障碍(MCI)是AD的高危人群。嗅觉障碍是MCI的最早期临床表现。基于气味识别任务的fMRI能够显示嗅觉环路。目前MCI及AD嗅觉障碍的中枢机制以及嗅觉障碍在MCI向AD转化中的作用尚不明确。本课题组前期在550例MCI的研究中发现眶额叶、海马等嗅觉相关脑区存在结构损伤。我们假设嗅觉障碍及嗅觉环路的结构及功能异常能够早期预测AD。本研究采用嗅觉阈值仪评估MCI及AD的嗅觉阈值、识别及鉴别功能；采用结构MRI和基于气味识别与气味记忆任务的fMRI研究其嗅觉环路的结构萎缩模式和功能损伤特征，以期发现嗅觉环路的结构和功能变化与AD进展的相关性，从而阐明MCI和AD嗅觉障碍的中枢机制，寻找MCI向AD转化的嗅觉环路关键节点，获得AD早期诊断的影像学特征，为AD的预警和干预提供新思路。

阿尔茨海默病(AD)的早期诊断有利于改善患者的预后，AD 的早期诊断标记物是目前研究的热点。轻度认知障碍(MCI)是AD 的高危人群。嗅觉障碍是MCI 的最早期临床表现。基于气味识别任务的fMRI 能够显示嗅觉环路。目前MCI 及AD 嗅觉障碍的中枢机制以及嗅觉障碍在MCI 向AD 转化中的作用尚不明确。本课题组前期在550 例MCI 的研究中发现眶额叶、海马等嗅觉相关脑区存在结构损伤。本项目探究嗅觉障碍及嗅觉环路的结构及功能异常如何早期预测AD。本研究采用嗅觉阈值仪评估MCI 及AD 的嗅觉阈值、识别及鉴别功能；采用结构MRI 和基于气味识别与气味记忆任务的fMRI 研究其嗅觉环路的结构萎缩模式和功能损伤特征，我们发现嗅觉环路的结构和功能变化与AD 进展的相关性，从而阐明MCI 和AD 嗅觉障碍的中枢机制。同时，本项目在研究过程中针对嗅觉神经环路在功能磁共振成像领域受磁敏感伪影影响严重的技术问题，针对性的研究了嗅觉激活的可重复性，充分论证了嗅觉功能磁共振成像的技术稳定性和可靠性，为未来后继研究打下了基础。