Zeng Chaofan, Zhai Yuanren, Ge Peicong, Liu Chenglong, Yu Xiaofan, Liu Wei, Li Junsheng, He Qiheng, Liu Xingju, Ye Xun, Zhang Qian, Wang Rong, Zhang Yan, Zhang Dong, Zhao Jizong
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, No. 119 South 4th Ring West Road, Fengtai District, Beijing, 100070, China.
China National Clinical Research Center for Neurological Diseases, Beijing, China.
Transl Stroke Res. 2025 Jun;16(3):690-703. doi: 10.1007/s12975-024-01250-z. Epub 2024 Apr 17.
Glymphatic system alterations have been proved to be associated with cognitive dysfunction in neurodegenerative diseases. The glymphatic pathway has not been elucidated in moyamoya disease (MMD), which was recognized as a chronic hypoperfusion model for neurodegenerative disease. Here, we aimed to investigate the glymphatic system activity and its relation with neurocognition, and associated hallmarks in MMD. We prospectively recruited 30 MMD patients and 30 matched healthy controls (HC). Participants underwent MRI and neurocognition evaluation. The glymphatic function was assessed by diffusion tensor image analysis along perivascular space (DTI-ALPS) index. Gray matter volume (GMV) and microstructural alterations were calculated. Neurodegenerative-related serum biomarkers were examined. The mediation effect of ALPS index in the associations between variables and neurocognition were further explored. A lower ALPS index was identified in patients with MMD (P < 0.001). The decreased ALPS index was significantly correlated with declined neurocognitive performance. Moreover, the reduced ALPS index was notably linked with lower total GMV% and deep GMV% (P < 0.01). Microstructural changes in the periventricular areas were detected and associated with ALPS index in MMD. Serum neurodegenerative biomarkers (ApoE, Aβ40, Aβ42, and Aβ42/Aβ40) were significantly elevated and related to ALPS index. Additionally, the ALPS index significantly mediated the associations of microstructural alterations and ApoE level with neurocognitive dysfunction. The ALPS index was notably lower MMD in patients, suggesting the utility as a marker of potential glymphatic dysfunction. The index acted as a significant mediator in neurocognitive dysfunction. These findings indicated that glymphatic impairment may interact with MMD-related pathophysiological processes.
已证明淋巴系统改变与神经退行性疾病中的认知功能障碍有关。烟雾病（MMD）被认为是神经退行性疾病的慢性低灌注模型，其淋巴途径尚未阐明。在此，我们旨在研究MMD中淋巴系统的活性及其与神经认知的关系以及相关特征。我们前瞻性地招募了30例MMD患者和30例匹配的健康对照（HC）。参与者接受了MRI和神经认知评估。通过沿血管周围间隙的扩散张量图像分析（DTI-ALPS）指数评估淋巴功能。计算灰质体积（GMV）和微观结构改变。检测与神经退行性相关的血清生物标志物。进一步探讨了ALPS指数在变量与神经认知之间关联中的中介作用。MMD患者的ALPS指数较低（P < 0.001）。ALPS指数降低与神经认知表现下降显著相关。此外，ALPS指数降低与总GMV%和深部GMV%降低显著相关（P < 0.01）。在MMD中检测到脑室周围区域的微观结构变化并与ALPS指数相关。血清神经退行性生物标志物（ApoE、Aβ40、Aβ42和Aβ42/Aβ40）显著升高并与ALPS指数相关。此外，ALPS指数显著介导了微观结构改变和ApoE水平与神经认知功能障碍之间的关联。MMD患者的ALPS指数明显较低，表明其可作为潜在淋巴功能障碍的标志物。该指数在神经认知功能障碍中起重要中介作用。这些发现表明淋巴损伤可能与MMD相关的病理生理过程相互作用。
