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.