Chronic mountain sickness (CMS) is frequently accompanied by cognitive impairments, including memory loss and executive dysfunction, which seriously affect quality of life. Although extensive investigations have elucidated cardiopulmonary adaptations in CMS, the neuropathological substrates mediating cognitive impairment remain poorly characterized. This study investigated whether elevated hemoglobin/hematocrit (Hb/Hct) directly induces white matter (WM) injury and whether WM integrity mediates the Hb–cognition relationship. A case–control study was conducted with 20 CMS patients (Hb ≥ 20 g/dL, Hct ≥ 65%) and 20 matched healthy high-altitude residents, using multimodal assessments including diffusion tensor imaging (DTI), susceptibility-weighted imaging (SWI), cognitive testing, and hematological biomarkers. Results showed that Hb-related neurotoxicity, together with hemorheological disturbances, contributes to WM degeneration, which directly links erythrocytosis to cognitive decline in CMS. DTI-derived fractional anisotropy (FA) emerged as a potential early biomarker for CMS-related cognitive impairment and supports clinical interventions targeting Hct, such as considering phlebotomy when Hct reaches 58%.
Research Article
Open Access