帕金森病轻度认知障碍的嗅觉中枢神经损害机制的多模态fMRI研究

Parkinson's disease mild cognitive impairment (PD-MCI) is an early manifestation of PD cognitive impairment, and will likely progress to PD dementia (PDD). Olfactory dysfunction is the most common early non-motor symptoms of PD. Recently, studies suggest that hyposmia is closely related with PD-MCI and PDD, while the mechanisms involved are unclear. Multiple modal functional MRI (fMRI) can display the change of the structure and function of the olfactory central nervous. This study proposed to recruit patients of PD (normal cognitive function), PD-MCI and PDD, assess the cognitive function with cognitive rating scale;evaluate the olfactory threshold and odor recognition ability; inspect the characteristic changes of olfactory central structure and functional injury with the technique of structural, resting state and olfactory task state fMRI. Through longitudinal follow-up studies, the dynamic changes of olfactory central nerve injury in PD-MCI cognitive function were defined, and clarify the imageological mechanisms of olfactory central nerve damage in patients with PD-MCI. And finally, to explore the possibility of olfactory center damage model as a biomarker for prediction of cognitive function deterioration in PD-MCI.

帕金森病（PD）轻度认知障碍（MCI）是PD认知功能损害的早期表现，有进展为PD痴呆（PDD）的可能。嗅觉障碍是PD早期最常见的非运动症状，近年来研究显示嗅觉障碍与PD-MCI、PDD的发病密切相关，但其嗅觉中枢神经损伤的神经影像学机制尚不明确。基于嗅觉相关的多模态功能MRI（fMRI）能显示嗅觉中枢神经的结构及功能的改变。本研究拟纳入PD（认知功能正常）、PD-MCI及PDD患者，应用多维度的认知量表评估认知功能；采用嗅觉阈值仪评估受试者嗅觉阈值、识别功能；利用结构MRI、静息态及嗅觉任务态fMRI研究认知功能障碍的PD患者嗅觉中枢结构和功能损伤的特征性改变；通过纵向随访研究，明确嗅觉中枢神经损伤在PD-MCI认知功能进展中的动态变化。从而阐明PD-MCI患者嗅觉中枢神经损伤的影像学机制，探讨多模态fMRI所揭示的嗅觉中枢损伤模式作为预测PD-MCI认知功能转化进展的生物标志物的可能性。

帕金森病（PD）轻度认知障碍（MCI）是PD认知功能损害的早期表现，有进展为PD痴呆（PDD）的可能。嗅觉障碍是PD早期最常见的非运动症状，近年来研究显示嗅觉障碍与PD-MCI、PDD的发病密切相关，但其嗅觉中枢神经损伤的神经影像学机制尚不明确。本研究首先评估认知正常组及PD-MCI组嗅觉阈值，发现PD-MCI组嗅觉功能明显低于认知正常组。fMRI研究发现，PD-MCI组左侧上顶、右侧下顶、右侧上额等脑区的皮层厚度比认知正常组明显萎缩。白质纤维束FA值对比发现，PD-MCI组右侧扣带回FA值明显降低。小世界脑网络属性分析显示，两组在聚类系数（Cp）、全局效率和局部效率有下降趋势，最短路径长度（Lp）呈上升趋势，但两组间无显著性差异。在进行嗅觉刺激功能MRI分析时发现MCI组双侧额叶，左侧尾状核，右侧豆状核等脑区激活程度弱于正常认知组。通过本研究，部分阐述了认知功能障碍的PD患者嗅觉中枢神经损伤的影像学机制，为未来进一步探讨多模态fMRI预测PD-MCI认知功能转化进展的生物标志物提供依据。