Plasma Metabolomic Profiling Reveals Systemic Metabolic Dysregulation and Its Association with Cognitive Impairment in Moyamoya Disease

Moyamoya disease (MMD) is a progressive cerebrovascular disorder that accounts for a rare cause of ischemic, hemorrhagic stroke and cognitive impairment. However, the association between plasma metabolic changes and cognitive decline in patients with MMD has yet to be fully elucidated. Methods A total of 30 MMD patients with asymptomatic, ischemic and hemorrhagic subtypes and 10 healthy controls were recruited. Global and domain-specific cognitive functions were assessed. Plasma samples were subjected to untargeted Liquid chromatography–mass spectrometry (LC-MS/MS) metabolomics to identify metabolic disturbances. Multivariate statistical analyses and correlation analyses were performed to explore the association between metabolic profiles and cognitive deficits, and the metabolic changes among MMD subtypes. Results MMD patients presented obvious impairments in general cognition, immediate memory, delayed recall and recognition, with no cognitive differences across subtypes. In total, 120 upregulated and 22 downregulated plasma metabolites were identified in MMD. Key changes involved elevated bile acids, decreased purine nucleotides, and disrupted lipid and energy metabolism. 11-Cis-Retinol was closely correlated with cognitive dysfunction. Each subtype showed exploratory metabolic alterations: asymptomatic MMD showed disrupted bile acid and neurotransmitter metabolism; ischemic MMD displayed inflammatory imbalance and energy shortage; hemorrhagic MMD showed mitochondrial and metabolic dysfunction. Conclusion MMD is associated with cognitive impairment and systemic metabolic dysregulation. Exploratory subtype-related metabolic differences were observed, while abnormal bile acid metabolism and disrupted energy homeostasis may be associated with cognitive decline. This study may provide novel metabolic evidence and potential biomarkers for MMD classification and cognitive intervention.