Impact of high-altitude exposure on cerebral small vessel disease: a study based on neuroimaging markers and systemic inflammatory indices

Chronic hypoxia at high-altitude may modulate cerebral small vessel disease (CSVD); however, its effects on specific neuroimaging phenotypes remain poorly defined. We aimed to characterize altitude-related white matter hyperintensity (WMH) patterns and to examine their associations with systemic inflammatory markers. We retrospectively analyzed 309 patients with CSVD who underwent brain MRI. Participants were stratified by residential altitude into mid-altitude (1,800–2,500 m, n = 97), high-altitude (2,500–3,500 m, n = 123), and ultra-high-altitude (≥ 3,500 m, n = 89) groups. Quantitative MRI was used to assess total CSVD burden and regional WMH volumes and proportions in deep, juxtacortical, periventricular, and juxtaventricular white matter. Systemic inflammatory markers were collected. Multivariable linear regression was performed to identify independent predictors of WMH volumes. Total CSVD burden did not differ across altitude groups. Increasing altitude was associated with greater deep and juxtacortical WMH volumes and proportions, with the strongest effects observed at ultra-high-altitude. In contrast, periventricular and juxtaventricular WMH showed no altitude-related differences. Multivariable analyses identified age, altitude, hypertension, and elevated homocysteine levels as independent predictors of deep and juxtacortical WMH, whereas systemic inflammatory markers were not significantly associated. High-altitude exposure is associated with a distinct, region-specific WMH phenotype in CSVD, predominantly involving deep and juxtacortical white matter. These findings suggest that altitude-related hypoxia may exacerbate CSVD through vascular and metabolic vulnerability rather than systemic inflammatory mechanisms.