Cerebral hemodynamic changes at high altitude in adults: a systematic review and meta-analysis of transcranial...

Exposure to intermediate and high altitude induces hypobaric hypoxia, which may alter cerebral hemodynamics through complex interactions involving hypoxia-driven vasodilation, hypocapnia, hematologic changes, and vascular remodeling; however, cerebrovascular responses vary substantially between native high-altitude populations and lowlander individuals. We conducted a systematic review and meta-analysis to quantify altitude-related changes in cerebral blood flow (CBF) and related hemodynamic parameters and to explore sources of heterogeneity. Major databases were searched through inception to November 2025 for observational studies evaluating cerebral hemodynamics at ≥1,500 m above sea level. Outcomes included mean velocity (MV), volumetric blood flow, arterial diameter, cerebrovascular conductance, cerebral oxygen saturation, autoregulation index, and global CBF. Random-effects models (Paule-Mandel) were used to pool mean differences, with subgroup and metaregression analyses performed; certainty of evidence was assessed with GRADE. Fifty-five studies including 1,935 participants were analyzed. Altitude exposure was associated with a reduction in mean cerebral artery velocity [mean difference (MD) -5.79 cm/s; 95% confidence interval (CI) -9.37 to -2.21; I² = 96%], reduced volumetric blood flow (MD -32.99 mL/min; 95% CI -45.24 to -20.73; I² = 98%), decreased arterial diameter (MD -0.27 mm; 95% CI -0.45 to -0.08; I² = 91%), lower cerebrovascular conductance (MD -0.43 mL/min/mmHg; 95% CI -0.65 to -0.21; I² = 24%), reduced cerebral oxygen saturation (MD -4.45%; 95% CI -6.77 to -2.14; I² = 74%), and lower global cerebral blood flow (MD -155.00 mL/min; 95% CI -350.11 to 40.11; I² = 95%), although heterogeneity was substantial across outcomes. Subgroup analyses suggested that native high-altitude populations and lowlander individuals exhibit distinct cerebrovascular responses, with population status, age, and altitude level explaining part of the observed variability. Overall certainty of evidence was very low. These findings indicate that exposure to altitude is associated with heterogeneous but consistent alterations in cerebral hemodynamic parameters, with marked differences between native and nonnative populations, underscoring the importance of population-specific physiological adaptation when interpreting cerebrovascular responses to hypoxia.NEW & NOTEWORTHY In this first global meta-analysis of ultrasound-based cerebral hemodynamics at ≥1,500 m, we show that altitude exposure is associated with lower cerebral blood flow velocity, volumetric flow, arterial diameter, and oxygen saturation in healthy adults. Native status, age, and altitude level partly explain marked heterogeneity. These findings highlight distinct adaptive patterns between native and nonnative populations and underscore the need for standardized, longitudinal studies of brain perfusion at altitude.