Endothelium‐related biomarkers and cognitive decline in prevalent hemodialysis patients: A prospective cohort study

Introduction Cognitive decline is prevalent in maintenance hemodialysis patients. The blood–brain barrier has been implicated in cognitive decline. In this prospective cohort study, we investigated the associations between endothelium‐related biomarkers and steeper cognitive decline in this population. Methods Cognitive function was assessed using the Portuguese‐adapted Cambridge Cognitive Examination (CAMCOG) with items of the Mini‐Mental State Examination (MMSE). Endothelium‐related biomarkers included syndecan‐1, ICAM‐1, VCAM‐1 and angiopoietin‐2 (AGPT2). Patients were followed up for 4 years, and cognitive assessments were repeated. Multinomial regression analyses were performed to evaluate associations between biomarkers and cognitive decline. Results A total of 216 patients completed the test battery at baseline. After 4 years, 102 patients had follow‐up data. There was a significant decrease in cognitive function according to the CAMCOG and MMSE scores: a change of −0.39 (95% CI −0.27 to −0.51) and −0.51 (95% CI −0.27 to −0.76) standard deviation (SD) of the baseline scores. Additionally, executive function but not memory significantly decreased. Syndecan‐1 level was independently associated with steeper cognitive decline; each increase in the SD of the syndecan‐1 level was associated with a decrease in the CAMCOG of 0.20 (95% CI 0.07–0.33) SD from baseline. Syndecan‐1 was associated with a steeper decline in MMSE score (β 0.54, 95% CI 0.28–0.81) and executive function (β 0.17, 95% CI 0.02–0.32). Syndecan‐1 predicted severe cognitive impairment with an area under the curve for receiver operating characteristic curves of 0.75 (95% CI 0.64–0.83). Conclusion Our findings highlight the potential of syndecan‐1, a biomarker of endothelium glycocalyx derangement, as a predictor of steeper cognitive decline in prevalent hemodialysis patients.