White matter hyperintensities mediate the association between frailty and cognitive impairment in moyamoya disease

The relationship between cognitive function and frailty in moyamoya disease (MMD) remains unclear, and the underlying mechanism is poorly understood. This study aims to investigate whether white matter hyperintensities (WMHs) mediate the association between frailty and cognitive impairment in MMD. Patients with MMD were consecutively enrolled in our study from January 2021 to May 2023. Pre-admission frailty and cognition were assessed using the Clinical Frailty Scale (CFS) and cognitive tests, respectively. Regional deep WMH (DWMH) and periventricular WMH (PWMH) volumes were calculated using the Brain Anatomical Analysis using Diffeomorphic deformation toolbox based on SPM 12 software. Multivariate logistic regression analysis was conducted to evaluate the association between frailty and cognitive function in MMD. Mediation analysis was performed to assess whether WMHs explained the association between frailty and cognition. A total of 85 patients with MMD were enrolled in this study. On the basis of the CFS scores, 24 patients were classified as frail, 38 as pre-frail, and 23 as robust. Significant differences were observed in learning, memory, processing speed, executive functions, and semantic memory among the three groups (p < 0.001). Frailty was independently associated with memory and executive functions (p < 0.05); even after controlling for WMH. Mediation analysis indicated that the associations of frailty with memory and executive functions were partially mediated by WMH, DWMH, and PWMH (p < 0.05). Frailty is significantly correlated with a higher risk of cognitive impairment in MMD, even after adjusting for other covariates. WMHs partially mediate the association between frailty and cognitive impairment.