Cerebrovascular Pulsatility Index Is Reduced in Autosomal Dominant Polycystic Kidney Disease

Abstract

<b><i>Introduction:</i></b> 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. <b><i>Methods:</i></b> 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 CO<sub>2</sub>, cerebrovascular reactivity) in patients with early-stage ADPKD versus age-matched healthy controls. We also administered the NIH cognitive toolbox (cognitive function) and measured carotid-femoral pulse-wave velocity (PWV, aortic stiffness). <b><i>Results:</i></b> Fifteen participants with ADPKD (9F, 27 ± 4 yrs, eGFR: 106 ± 22 mL/min/1.73 m<sup>2</sup>) were compared to 15 healthy controls (8F, 29 ± 4 yrs, eGFR: 109 ± 14 mL/min/1.73 m<sup>2</sup>). MCA PI was unexpectedly lower in ADPKD (0.71 ± 0.07) versus controls (0.82 ± 0.09 AU; <i>p</i> < 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 %Δ/mm Hg; <i>p</i> = 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, <i>p</i> = 0.007). There was no association of MCA PI with carotid-femoral PWV (<i>r</i> = 0.01, <i>p</i> = 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. <b><i>Discussion/Conclusion:</i></b> 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.