The association between altitude and cerebral small vessel disease burden in the Tibetan population: a cross-sectional study.

Cerebral small vessel disease (CSVD) is a major neurovascular contributor to stroke and cognitive impairment, yet its interaction with chronic high-altitude adaptation remains poorly understood. This first neuroimaging investigation examined 499 Tibetan natives residing at 2000-4800 m using 3 T MRI to quantify CSVD burden and to assess its association with residential altitude. Multivariable logistic regression, treating altitude as both a continuous variable (per 500 m increment) and a categorical variable (mid-high [2000-3500 m] vs. ultra-high [> 3500 m]), revealed that 51.5% of participants had CSVD (CSVD score ≥ 1), with adjusted odds ratios of 0.94 (95% CI: 0.74-1.21) per 500 m altitude and 0.78 (95% CI: 0.42-1.44) for ultra-high versus mid-high altitude. Partial proportional odds model showed no significant association between altitude and CSVD score (OR = 1.18, 95% CI 0.99-1.40). These null findings, in contrast to the well-established paradoxical impact of altitude on stroke risk, suggest potential neuroprotective mechanisms in altitude-adapted populations. Our results challenge conventional cerebrovascular paradigms and highlight the need for further research into Tibetan-specific genetic adaptations that may modulate CSVD pathophysiology. This study provides essential insights for refining altitude-related cerebrovascular risk models.