Frailty, which is characterized by a gradual deterioration of multiple physiological systems, has recently garnered increasing attention not only in older individuals but also in younger adults with comorbidities [1], [2]. It often coexists with diseases associated with a higher risk of poor prognosis [3], [4].

Studies have highlighted the significant role of frailty in cognitive decline among older individuals [5], [6]. For instance, cross-sectional research has shown a notable interaction between frailty and Alzheimer disease pathology [7]. In the realm of cerebrovascular diseases, frailty has been positively correlated with the incidence of post-stroke cognitive impairment and stroke outcomes [8]. Moreover, findings from a large sample in UK Biobank indicate that a significant association exists between the severity of frailty and the burden of white matter hyperintensities (WMHs) [9]. WMHs are well-established risk factors for cognitive impairment both in older participants without dementia and patients diagnosed with cerebrovascular diseases [10].

Moyamoya disease (MMD) is a rare cerebrovascular condition characterized by low cerebral perfusion due to bilateral steno-occlusion of the internal carotid artery; and often results in abnormal vascular network formation [11]. Although there is mounting evidence regarding the relationships among revascularization, WMHs, cerebral perfusion, and cognitive function in MMD, few clinical studies have investigated the effect of frailty on cognition in this context [12], [13]. The potential mechanism linking frailty and cognition remains unclear. Our study hypothesizes that WMHs may mediate the correlation between pre-admission frailty and cognitive impairment in patients with MMD.