Arterial Stiffness and Cognitive Decline in the Chronic Renal Insufficiency Cohort (CRIC) Study

Background: Kidney function decline is associated with impaired cognitive function, and there is evidence that higher carotid-femoral pulse-wave velocity (PWV), a measure of arterial stiffness, is associated with cognitive impairment in non-chronic kidney disease (CKD) studies. However, it has yet to be investigated if PWV is predictive of incident cognitive impairment in patients with CKD. We hypothesized that higher PWV is associated with a decline in cognitive function over time in adults with CKD who participated in the CRIC study. Methods: We included 1,864 participants from the observational cohort study, CRIC, with baseline carotid-femoral PWV measurements and no baseline cognitive impairment, defined as Modified Mini-Mental State Examination (MMSE) score >1 SD below the cohort mean at baseline. Cox proportional hazard regression was used to examine the association between PWV and time to cognitive impairment, defined as a decline in MMSE scores of >1.0 SD below the cohort mean (determined from baseline cognitive scores). Results: Participants were 58±11 years old, 56% (n=1048) were male, baseline estimated glomerular filtration rate (eGFR) was 47±15 ml/min/1.73m2, baseline carotid-femoral PWV was 10.7±3.7 m/s, and baseline MMSE score was 94.9±4.3. During a follow-up of 9.1±4.6 years, 280 participants (15%) had a clinically significant decline in MMSE score (i.e. incident cognitive impairment). After adjustment for age, sex, race/ethnicity, education, and baseline MMSE there was a significantly greater risk of incident cognitive impairment (Hazard Ratio [HR]: 1.04, 95% CI: 1.00-1.07 per 1 unit increase in PWV). However, this association was attenuated after further adjustment for systolic blood pressure, hypertension, diabetes, cardiovascular disease history, alcohol use, stroke history, smoking status, body-mass index, antihypertensive and anticoagulant usage, eGFR, and 24-hour albuminuria (HR: 1.02 [0.98, 1.06]). Conclusion: In adults with mild to moderate CKD higher PWV was associated with a greater risk of incident cognitive impairment; however, this association was no longer significant after full adjustment for covariates. Funding: NIDDK Support