Abstract
High-altitude environments pose significant challenges to human cognition due to hypoxic conditions. The long-term effects of chronic high-altitude exposure on cognitive functions remain poorly understood. Cognitive decline in this age group may compromise academic performance, occupational safety and future productivity. In this 4-year longitudinal study, we examined 69 college freshmen who relocated from sea level to the high-altitude region of Tibet. Over four years, we conducted comprehensive cognitive assessments and brain MRI scans at baseline, year two, and year four. Behavioral data revealed persistent impairments in cognitive functions such as working memory and psychomotor function among those exposed to high altitudes for extended periods. Neuroimaging analyses demonstrated a notable decrease in gray matter volume and resting-state brain activities, specifically in the left putamen. These neural alterations were significantly correlated with the observed cognitive deficits, and importantly, the effect of exposure time on working memory was mediated by the left putamen volume. Chronic high-altitude exposure in otherwise healthy young adults is associated with enduring cognitive deficits and convergent structural and functional alterations in the left putamen. These findings highlight cognitive health as an important but under-recognized public-health concern in populations who study or work at high altitude, and suggest that monitoring and preventive strategies may be warranted for long-term high-altitude migrants. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-026-42645-2.