Li Ling-Ling, Ma Jie, Wu Jia-Jia, Xue Xin, Zheng Mou-Xiong, Hua Xu-Yun, Guo Qi-Hao, Xu Jian-Guang
Department of Rehabilitation Medicine, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 200437, China.
School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Alzheimers Res Ther. 2025 Mar 21;17(1):66. doi: 10.1186/s13195-025-01717-7.
The formation and retrieval of episodic memory is dependent on the coordinated activity of multiple brain regions and neural networks, with the Papez circuit playing a critical role in this process. Recently, the role of the perivascular space (PVS) in cognitive function has garnered increasing attention. However, the role of PVS function between neural circuits and cognitive function in amnestic mild cognitive impairment (aMCI) patients remains unknown. Therefore, this study aims to (1) investigate alterations in the effective connectivity of the Papez circuit and PVS function in patients with aMCI and (2) explore the role of PVS function between the effective connectivity of the Papez circuit and episodic memory.
Sixty participants, all of whom underwent multimodal MRI (fMRI, dMRI, and sMRI) and neuropsychological testing, were recruited for this case‒control study. General linear models were used to compare the effective connectivity within the Papez circuit and PVS function between aMCI patients and healthy controls (HCs) and further explore the role of PVS function between the effective connectivity within the Papez circuit and episodic memory.
The effective connectivity between multiple critical regions within the Papez circuit, notably in the hippocampus, anterior cingulate cortex, and parahippocampal gyrus, was significantly weakened in aMCI patients. Moreover, a significant reduction in the along the perivascular space (ALPS) index was observed among aMCI patients, accompanied by a marked increase in PVS volume, indicating significant PVS dysfunction. Further moderation analysis revealed that PVS function moderated the relationship between effective connectivity within the Papez circuit and episodic memory.
The effective connectivity within the Papez circuit and PVS function are closely related to cognitive function, particularly episodic memory, and enhancing PVS function may serve as a novel therapeutic target for slowing cognitive decline.
情景记忆的形成与提取依赖于多个脑区和神经网络的协同活动，其中帕佩兹环路在此过程中发挥着关键作用。近来，血管周围间隙（PVS）在认知功能中的作用日益受到关注。然而，PVS功能在遗忘型轻度认知障碍（aMCI）患者的神经回路与认知功能之间的作用仍不清楚。因此，本研究旨在：（1）调查aMCI患者帕佩兹环路的有效连接性及PVS功能的改变；（2）探讨PVS功能在帕佩兹环路有效连接性与情景记忆之间的作用。
本病例对照研究招募了60名参与者，他们均接受了多模态MRI（功能磁共振成像、扩散张量成像和结构磁共振成像）及神经心理学测试。采用一般线性模型比较aMCI患者与健康对照（HCs）之间帕佩兹环路内的有效连接性及PVS功能，并进一步探讨PVS功能在帕佩兹环路内有效连接性与情景记忆之间的作用。
aMCI患者帕佩兹环路内多个关键区域之间的有效连接性显著减弱，尤其是在海马体、前扣带回皮质和海马旁回。此外，aMCI患者的血管周围间隙沿线（ALPS）指数显著降低，同时PVS体积显著增加，表明存在明显的PVS功能障碍。进一步的调节分析显示，PVS功能调节了帕佩兹环路内有效连接性与情景记忆之间的关系。
帕佩兹环路内的有效连接性及PVS功能与认知功能密切相关，尤其是情景记忆，增强PVS功能可能成为减缓认知衰退的新治疗靶点。
