Papez circuit remodeling in type 2 diabetes: Enlarged choroid plexus volume partially mediates functional impairments linked to insulin resistance

作者：Yujie Zhang, Shuyue Fan, Huiyou Chen, Fengfang Li, Wen Geng, Mingxu Jin, Cunnan Mao, Rong Huang, Wenqing Xia, Xindao Yin · 发表于：NeuroImage · 年份：2025 · DOI：10.1016/j.neuroimage.2025.121544 · 被引用次数：4 · 研究领域：Cerebrospinal fluid and hydrocephalus、Dementia and Cognitive Impairment Research、Functional Brain Connectivity Studies

AIM: Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with cognitive decline. This study investigated the interplay between altered effective connectivity (EC) in the Papez circuit, regional atrophy, and choroid plexus volume (CPV) in relation to T2DM-related cognitive deficits. METHODS: Eighty T2DM patients and 75 healthy controls underwent multimodal MRI. Resting-state fMRI data were analyzed using spectral dynamic causal modeling (spDCM) to quantify EC between Papez circuit regions. Structural 3D-T1 images were processed to measure regional volumes and the CPV, which might serve as a proxy for glymphatic activity. Participants underwent standardized cognitive assessments to evaluate neurocognitive function. RESULTS: T2DM patients exhibited significant EC reductions in three Papez circuit pathways: from the hippocampus (HPC) to the mammillary body (MB) (p = 0.001), from the anterior thalamic nucleus (AT) to the anterior cingulate cortex (ACC) (p = 0.005), and from the entorhinal cortex (ERC) to the HPC (p < 0.001). Structural atrophy was observed in the left hippocampus (p = 0.001) and left thalamic (p = 0.006), accompanied by CPV enlargement (p = 0.027). Notably, the HPC to MB connectivity was partially mediated by the CPV, with a significant indirect effect of 0.1456 (95 % CI: 0.0335, 0.2665). The Complex Figure Test delay (CFT-delay) score was positively correlated with the reduced EC in Papez circuit pathways; however, there was a negative correlation ...