The Impact of High-Altitude Acclimatization on Frontal Lobe Executive Function: The Mediating Effect of Creatinine

OBJECTIVE: Highaltitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine mediates the relationship between altitude acclimatization (AAI) SpO₂/HCT ratio and frontal neural oscillations. METHODS: In 190 adults at 3,650 m (Lhasa), we measured SpO₂, hematocrit, serum creatinine, and restingstate frontal EEG. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Zstandardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via creatinine. RESULTS: AAI significantly negatively predicted creatinine (p < 0.001). Creatinine significantly negatively predicted frontal ZPSD in theta (4-7 Hz), alpha (8-13 Hz), and beta (14-30 Hz) bands (all p < 0.01), but not in other bands. The indirect effect via creatinine was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation). CONCLUSIONS: The kidneybrain axis mediates hypoxic neurocognitive adaptation with frequencyspecific patterns. Creatinine dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.