基于多模态PET/MRI对海马亚区-腹侧纹状体-前额叶神经环路在帕金森病认知障碍中作用机制的研究

帕金森病(Parkinson's disease,PD)认知障碍是非运动损伤中最常见的致残症状之一，明确其进展机制及寻找可靠的标志物对临床管理意义重大。研究证实，PD认知障碍患者海马并非同质性的损伤，不同亚区间存在差异，因此，将其作为一个整体研究并不能阐明其作用，且海马亚区-腹侧纹状体-前额叶环路损伤模式仍不清楚。申请者前期发现了该环路损伤的一些特征：海马角1区是早期萎缩亚区；随着PD认知损伤进展，海马角与前额叶及壳核功能连接从减低到增高；轻度认知障碍患者腹侧纹状体多巴胺转运体水平增高且与认知相关。因此，我们假设PD认知障碍演变中海马亚区-腹侧纹状体-前额叶环路损伤存在差异，多巴胺能在早期就参与认知调节，海马角1区损伤可能是疾病进展的标志物。本项目将联合多模态PET/MRI，从分子、功能及结构水平研究上述环路的损伤模式及多巴胺能对其调节作用，以期为临床提供PD认知损伤进展的客观证据。

Cognitive impairment is one of the most common disabling symptom in non-motor features of Parkinson's disease (PD). The core of clinical management depends on elucidating the progress mechanism and objective assessment. Although hippocampus has been proved to be involved in the progression of cognitive impairment of PD, its subfields are heterogeneously damaged, which means considering the hippocampus as a solitude entity may not adequately elucidate its function in PD. Moreover, the injury patterns and regulatory mechanisms of different hippocampal subfields-ventral striatum-prefrontal loop remains equivocal. Our previous research found several features in the hippocampal subfields-ventral striatum-prefrontal loop. Firstly, we found that the alteration of grey matter volume differed in hippocampal subfields in patients with cognitive impairment, with cornu ammonis-1 reduction in the early stage; secondly, our results showed that functional connectivity between the cornu ammonis and prefrontal cortex and putamen increased in patients with cognitive dysfunction, while functional connectivity between cornu ammonis and prefrontal cortex decreased in patients without cognitive impairment. Thirdly, the dopamine transporter of the ventral striatum was significantly increased in patients with mild cognitive impairment of PD, as well as associated with cognitive rating scores. Thus, we hypothesized that injury of the different hippocampal subfields-ventral striatum-prefrontal loop may vary in patients with cognitive impairment, which would be influenced by dopaminergic alteration in the early stage. The cornu ammonis-1 may be an early vulnerable subregion and a biomarker of progression of the disease. Taking advantage of multi-modal PET/MRI techniques, we will explore the functional and structural changes of the different hippocampal subfields-ventral striatum-prefrontal loop and the effect of dopaminergic alteration, which could revealed the injury patterns as well as regulatory mechanisms of the hippocampus, hoping to provide objective proof of progression for clinical management.