Multimodal MRI Combined with Cognitive Evaluation Reveals Glymphatic System Impairment in Moyamoya Vasculopathy

The aim of this research is to fully assess glymphatic system impairment in moyamoya vasculopathy (MMV) patients with a set of multi-modal MRI biomarkers that capture crucial functional processes: cerebrospinal fluid (CSF) influx, interstitial fluid exchange (free water in white matter, FW-WM), and downstream metabolite efflux (diffusion tensor imaging along the perivascular space, DTI-ALPS), and to explore their association with cognitive performance.

In this case-control study, 22 patients with MMV and 22 healthy controls (HCs) underwent 3T MRI with T1-weighted imaging and diffusion tensor imaging (DTI), as well as the Montreal Cognitive Assessment (MoCA). Total intracranial volume (ICV), choroid plexus volume (CPV), and CSF volume were quantified, with CPV/ICV and CSF/ICV ratios subsequently derived from these volumetric measurements. The FW-WM and DTI-ALPS indices were also calculated from DTI datasets. We further performed group-wise comparisons of all biomarkers and analyzed their correlations with MoCA-assessed cognitive performance.

MMV patients displayed impairments across multiple stages of the glymphatic pathway. CSF inflow was elevated, reflected by significantly increased CPV/ICV (0.157 ± 0.039% vs. 0.122 ± 0.033%, p = 0.002) and CSF/ICV (23.29 ± 2.73% vs. 20.70 ± 2.22%, p < 0.001). The FW-WM of MMV was significantly higher than that of HCs (0.20 ± 0.04 vs. 0.16 ± 0.02, p < 0.001). The ALPS index of MMV was significantly lower than that of HCs (1.31 ± 0.12 vs. 1.49 ± 0.06, p < 0.001). High intercorrelations between these biomarkers (p < 0.05) supported a systemic disturbance. Cognitive performance positively correlated with the ALPS index (r = 0.588, p = 0.004) and negatively with FW-WM, CPV/ICV, and CSF/ICV (r = -0.441 to -0.661, p < 0.05).

The results suggest a broad impairment of the glymphatic system across multiple functional stages in MMV, which is associated with cognitive decline.

Multimodal MRI reveals extensive changes in the glymphatic system of MMV patients, including increased CSF inflow, disrupted interstitial fluid exchange, and impaired clearance. These findings together could account for the cognitive impairments observed in this patient population.