Yao Shaoli, Qi Zhen-Rong, Bao Shi-Min, Xing Yi-Yin, Feng Hui-Ru, Tan Yuling, Zhang Qi, Ge Wei-Hong, Chen Xiaorong
Department of Neurology, Hospital of Chengdu Office of People's Government of Tibetan Autonomous Region, No. 20, Ximianqiao Street, Chengdu, 610041, Sichuan, China.
Sci Rep. 2025 Jul 5;15(1):24035. doi: 10.1038/s41598-025-09891-2.
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.
脑小血管病（CSVD）是导致中风和认知障碍的主要神经血管因素，但其与慢性高原适应的相互作用仍知之甚少。这项首次神经影像学研究对居住在2000 - 4800米的499名藏族原住民进行了检查，使用3T磁共振成像（MRI）来量化CSVD负担，并评估其与居住海拔的关联。多变量逻辑回归分析将海拔既视为连续变量（每增加500米）又视为分类变量（中高海拔[2000 - 3500米]与超高海拔[>3500米]），结果显示51.5%的参与者患有CSVD（CSVD评分≥1），海拔每500米调整后的优势比为0.94（95%置信区间：0.74 - 1.21），超高海拔与中高海拔相比的调整后优势比为0.78（95%置信区间：0.42 - 1.44）。部分比例优势模型显示海拔与CSVD评分之间无显著关联（优势比=1.18，95%置信区间0.99 - 1.40）。这些阴性结果与海拔对中风风险已明确的矛盾影响形成对比，提示在适应高原的人群中可能存在潜在的神经保护机制。我们的结果挑战了传统的脑血管范式，并强调需要进一步研究可能调节CSVD病理生理学的藏族特异性基因适应。这项研究为完善与海拔相关的脑血管风险模型提供了重要见解。
