101 Glymphatic System Impairment Associated With Neurocognitive Dysfunction and Alzheimers Biomarkers in Moyamoya Disease

Abstract

INTRODUCTION: Glymphatic system alterations have been proved to be associated with cognitive dysfunction in Alzheimer’s Disease (AD). The glymphatic pathway has not been elucidated in moyamoya disease (MMD), which was recognized as a chronic hypoperfusion model for AD. METHODS: We prospectively recruited 30 MMD patients and 30 matched healthy controls (HC) from October 2022 to March 2023. Participants underwent neurocognition evaluation, and multimodal magnetic resonance imaging (MRI). AD-related serum biomarkers, as well as correlations among these variables were examined. The glymphatic function was assessed by diffusion tensor image analysis along perivascular space (DTI-ALPS). Whole-brain (white matter and grey matter) volumes were calculated by using 3D T1-weighted MRI. Microstructural changes of white matter (intracellular volume fraction, Vic; orientation dispersion index, OD) were evaluated by neurite orientation dispersion and density imaging (NODDI). RESULTS: Serum Alzheimer’s biomarkers (ApoE, Aβ40, Aβ42, and tau) were significantly elevated and associated with neurocognitive dysfunction in MMD. Lower periventricular ALPS-index was identified in patients with MMD (P < 0.001). The decreased ALPS-index correlated with declined neurocognitive performance of intelligence quotient, attention, and memory, increased levels of serum ApoE, Aβ40, Aβ42, as well as higher periventricular white matter volume and lower periventricular grey matter volume (P < 0.001). Moreover, MMD patients had significantly lower Vic in the white matter and a lower OD in the cortex than HC. CONCLUSIONS: We firstly demonstrated the impaired glymphatic system as assessed by lower ALPS-index in patients with MMD. Glymphatic impairment was associated with AD-related biomarkers and cognitive dysfunction in MMD. These findings suggested that glymphatic disorder may interact with MMD-related pathophysiological processes.