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

High-altitude hypoxia impairs frontal executive functions. This study examines whether serum creatinine (CR) mediates the relationship between altitude acclimatization (AAI) peripheral oxygen saturation (SpO₂)/hematocrit (HCT) ratio and frontal neural oscillations.

In 190 adults at 3,650 m (Lhasa), we measured SpO₂, hematocrit, CR, and resting-state frontal electroencephalography. Power spectral density was calculated across multiple frequency bands (1-80 Hz) and Z-standardized. Mediation analysis with bootstrap tested the indirect effect of AAI on each band via CR.

AAI significantly negatively predicted CR (p < 0.001). CR significantly negatively predicted frontal Z-PSD 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 CR was significant for theta (p = 0.011, partial mediation), alpha (p = 0.031, full mediation), and beta (p = 0.020, full mediation).

The kidney-brain axis mediates hypoxic neurocognitive adaptation with frequency-specific patterns. CR dynamics reflect acclimatization efficacy, suggesting a target for preserving frontal executive function at high altitude.