Structural and load-dependent arterial stiffness are associated with cerebrovascular and cognitive outcomes in patients with chronic kidney disease

Aortic stiffness, an independent predictor of cardiovascular outcomes and death, is determined by structural (intrinsic remodeling of the arterial wall) and load-dependent (blood pressure loading on the arterial wall) mechanisms. Patients with chronic kidney disease (CKD) present with increased aortic stiffness; however, it is unknown whether specific mechanisms of aortic stiffness are associated with cerebrovascular and cognitive function and whether these associations differ from older controls without CKD. We hypothesized structural arterial stiffness would be associated with incident cognitive impairment in patients with CKD. Additionally, we expected patients with CKD would have greater structural and load-dependent arterial stiffness than older controls, with stronger associations between the arterial stiffness components and cerebrovascular/cognitive function in patients with CKD relative to older controls. We first evaluated the association of structural and load-dependent carotid-femoral pulse wave velocity (cfPWV) with incident cognitive impairment (defined as a decline in modified mini-mental state examination score to < 1 standard deviation below the cohort mean at baseline; Cox proportional hazards models) among 1367 participants (mean±sd; age:57.5±10.8, eGFR:47.7±15.3) enrolled in the observational Chronic Renal Insufficiency Cohort (CRIC). Next, associations between CKD, structural and load-dependent cfPWV and functional assessments of cerebrovascular and cognitive function (baseline assessments of pooled clinical trials in healthy older adults [n= 115] and patients with stage 3-4 CKD [n=107]) were assessed using multiple linear regression. Over a median follow-up of 11.6 years, cfPWV and load-dependent cfPWV were not associated with incident cognitive impairment; however, structural cfPWV was associated with a higher risk of incident cognitive impairment after adjusting for age, demographics, baseline cognitive function, cardiovascular risk factors and kidney function. Doubling of structural cfPWV was associated with a 47% increase in risk of cognitive impairment (hazard ratio: 1.47 [95% confidence interval: 1.09, 1.98]). Cross-sectionally, CKD was significantly associated with greater structural and load-dependent cfPWV, after adjusting for age, sex, and body mass index. Structural and load-dependent cfPWV were significantly associated with measures of cerebrovascular and cognitive function in patients with CKD, but these associations were not present in healthy older adults. Middle cerebral artery pulsatility index was positively associated with structural cfPWV, and cerebrovascular reactivity was positively associated with load-dependent cfPWV in patients with CKD; however, there was no association with cfPWV. Crystallized cognition composite score was negatively associated with load-dependent cfPWV in patients with CKD but was not associated with cfPWV. In conclusion, separating the components of cfPWV into structural and load-dependent cfPWV may provide further insight on risk of cerebrovascular and cognitive dysfunction in patients with CKD. Funding sources: This work was supported by NIH NIDDK, NIA, and NHLBI, and the American Society of Nephrology. This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.