Glymphatic Impairment Associated with Neurocognitive Dysfunction in Moyamoya Disease

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.