Supplementary Material for: Cerebrovascular Pulsatility Index is Reduced in Autosomal Dominant Polycystic Kidney Disease

Introduction: Cerebrovascular dysfunction, characterized by increased brain pulsatile flow, reduced cerebrovascular reactivity, and cerebral hypoperfusion precedes the onset of dementia and is linked to cognitive dysfunction. Autosomal dominant polycystic kidney disease (ADPKD) may increase the risk of dementia, and intracranial aneurysms are more prevalent in ADPKD patients. However, cerebrovascular function has not been previously characterized in patients with ADPKD. Methods: Using transcranial Doppler, we compared middle cerebral artery (MCA) pulsatility index (PI; cerebrovascular stiffness) and MCA blood velocity response to hypercapnia (normalized for blood pressure and end-tidal CO2; cerebrovascular reactivity) in patients with early-stage ADPKD vs. age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function) and measured carotid-femoral pulse-wave velocity (PWV; aortic stiffness). Results: Fifteen participants with ADPKD (9F, 27±4 yrs, eGFR: 106±22 ml/min/1.73m2) were compared to 15 healthy controls (8F, 29±4 yrs, eGFR: 109±14 ml/min/1.73m2). MCA PI was unexpectedly lower in ADPKD (0.71±0.07) vs. controls (0.82±0.09 A.U.; p<0.001); however, normalized MCA blood velocity in response to hypercapnia did not differ between groups (2.0±1.2 vs. 2.1±0.8 %△/mmHg; p=0.85). Lower MCA PI was associated with a lower crystalized composite score (cognition), which persisted after adjustment for age, sex, eGFR, and education (β = 0.58, p=0.007). There was no association of MCA PI with carotid-femoral PWV (r=0.01, p=0.96), despite greater carotid-femoral PWV in ADPKD, suggesting MCA PI reflects vascular properties other than arterial stiffness (such as low wall shear stress) in ADPKD. Discussion/Conclusion: MCA PI is lower in patients with ADPKD. Follow-up research on this observation is merited, as low PI has been associated with intracranial aneurysm in other populations.

**引言**：以脑脉动血流增加、脑血管反应性降低及脑低灌注为特征的脑血管功能障碍，先于痴呆发病，并与认知功能障碍相关。常染色体显性遗传性多囊肾病（Autosomal dominant polycystic kidney disease, ADPKD）可能增加痴呆发病风险，且ADPKD患者颅内动脉瘤患病率更高。但此前尚未有针对ADPKD患者脑血管功能特征的相关研究。

**方法**：本研究采用经颅多普勒超声，对比早期ADPKD患者与年龄匹配的健康对照者的大脑中动脉（middle cerebral artery, MCA）搏动指数（pulsatility index, PI，用于反映脑血管僵硬度），以及高碳酸血症下MCA血流速度响应（已针对血压及潮气末二氧化碳进行标准化校正，即脑血管反应性）。同时采用美国国立卫生研究院认知工具箱（NIH cognitive toolbox）评估认知功能，并测量颈股动脉脉搏波速度（carotid-femoral pulse-wave velocity, PWV，用于反映主动脉僵硬度）。

**结果**：本研究纳入15例ADPKD患者（9名女性，年龄27±4岁，估算肾小球滤过率eGFR：106±22 ml/min/1.73m²），并与15名健康对照者（8名女性，年龄29±4岁，eGFR：109±14 ml/min/1.73m²）进行对比。ADPKD患者的MCA PI显著低于对照组（0.71±0.07 vs 0.82±0.09 任意单位，p<0.001）；但两组间高碳酸血症下标准化MCA血流速度无显著差异（2.0±1.2 vs 2.1±0.8 %△/mmHg，p=0.85）。较低的MCA PI与更低的晶体化综合认知评分相关，在校正年龄、性别、eGFR及教育程度后，该关联仍具有统计学意义（β=0.58，p=0.007）。尽管ADPKD患者的颈股动脉PWV更高，但MCA PI与颈股动脉PWV无显著关联（r=0.01，p=0.96），提示ADPKD患者的MCA PI反映的是动脉僵硬度以外的血管特性（如低壁切应力）。

**讨论与结论**：ADPKD患者的MCA PI水平更低。鉴于低PI在其他人群中与颅内动脉瘤相关，针对该发现的后续研究具有重要价值。