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.