Abstract

Abstract BACKGROUND AND AIMS Chronic kidney disease (CKD) is a risk factor for cognitive impairment. In the general population, many risk factors have been reported in association with incident major neurocognitive disorders. The link between CKD and cognitive dysfunction is not completely understood; it may involve different mechanisms such as vascular dysfunction or uremic toxin toxicity. We aimed to assess the influence of cardiovascular risk factors, cardiovascular disease and depression on the association between kidney function and cognitive function in patients with CKD. METHOD We analyzed baseline data from 3033 patients with CKD stage 3–5 included in the Chronic Kidney Disease-Renal Epidemiology and Information Network (CKD-REIN) cohort between 2013 and 2016. Cognitive function was assessed with the Mini Mental State Examination (MMSE), and the glomerular filtration rate was estimated with the CKD EPI formula. We applied unadjusted and adjusted linear and logistic regression models, with the MMSE score as a continuous or categorical variable (at a cut-off point at 24/30). RESULTS The mean patient age was 66.8, the mean estimated glomerular filtration rate (eGFR) was 33 mL/min/1.73 m2 and 393 patients (13.0%) had a MMSE score <24. We observed that, relative to patients with an MMSE score of 24 or more, patients with a score <24 were older and more likely to be female and dependent on activities of daily living (ADL) and/or instrumental ADL. They were taking more medications and they were more affected by depressive symptoms as measured by the CES-D-10 (10 item Centre for Epidemiological Studies-Depression scale). Patients with a score <24 were also more likely to present cardiovascular (CV) risk factors and CV comorbidities. They had a significantly higher parathyroid hormone level, lower haemoglobin, lower albumin and lower eGFR. The eGFR was positively associated with the MMSE score before and after adjustment for age, sex, education level, cardiovascular risk factors, cardiovascular disease and depression, giving point increases in the MMSE score of 0.24 (0.15–0.33; P < .001) and 0.14 (0.04–0.23; P = .006) for a 10 mL/min/1.73 m2 increment in the eGFR, respectively. Other risk factors significantly associated with a lower MMSE score in multivariate analysis were age, female sex, lower educational level, diabetes, obesity, cerebrovascular disease, atrial fibrillation and CES-D-10 score. The eGFR was associated with a low MMSE score (defined as MMSE score <24/30) with a crude odds ratio (OR) of 0.82 (0.75–0.90), which remained significant at 0.88 (0.78–0.98) after adjustment for age, sex, educational level, cardiovascular risk factors (hypertension, diabetes mellitus, dyslipidaemia, obesity and smoking), cardiovascular comorbidities (cerebrovascular disease, atrial fibrillation and heart failure), history of depression, laboratory parameters (haemoglobin and phosphate) and CES-D score (after imputation of missing values). CONCLUSION In a cohort of well-phenotyped patients with CKD, lower eGFR is associated with worse cognitive function, independent of age, sex, educational level, cardiovascular injury and depression.

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