High-Altitude Exposure: Effects on Cognitive Performance, Neurovascular Mechanisms, and Mitigation Strategies

Abstract

Travel to and work at high altitudes expose individuals to hypobaric hypoxia; however, its effects on neural activity and function remain insufficiently understood. Here, we present findings from a longitudinal panel study incorporating oxygen supplementation tests in individuals who traveled from low altitude (Beijing, ∼50 meters above sea level (m.a.s.l.)) to high altitude (Xizang, 3600–5000 m.a.s.l.) and subsequently returned to low altitude. Upon ascent from low to high altitude, peripheral oxygen saturation decreased by approximately 10.5 percentage points, accompanied by a 2.48-point increase in Acute Mountain Sickness symptom scores. The odds of CRTT errors increased at Visit 2 (OR = 3.21), and the odds of Stroop errors increased at Visits 3–5 (ORs of 2.11–2.16). Additionally, the relative cerebral deoxygenated hemoglobin (ΔHbR) signal increased by 3.0 μM·mm during tests. Serum analysis revealed a 390.1 pg/mL increase in chitinase-3-like protein 1 (CHI3L1), indicating inflammatory activation, and a 37.1 pg/mL compensatory rise in brain-derived neurotrophic factor (BDNF). Mediation analyses suggested an indirect association of high-altitude exposure with Stroop errors through ΔHbR. Furthermore, our findings suggested that a few minutes of oxygen supplementation at high altitude may improve cerebral oxygenation, with behavioral changes in a favorable but non-significant direction, while cognitive and neurovascular measures tended to move toward baseline after return to low altitude. These findings provide evidence that high-altitude exposure is associated with significant yet potentially reversible neurocognitive effects, underscoring the need for confirmation in larger cohorts and further evaluation of strategies to mitigate neurocognitive risks.