Abstract

Background Patients undergoing hemodialysis experience a greater risk of cognitive impairment than the general population, but limited data elucidates the biomarkers on this. We evaluated the association of bone turnover markers on cognitive function among 251 prevalent hemodialysis enrollees in a cross-sectional study. Methods 251 hemodialysis patients (median age = 57.8, 55% men) and 37 control subjects (mean age = 61.2, 56% men) without a prior stroke or dementia diagnosis were enrolled. Serum concentrations of 8 bone markers were analyzed as the association of cognitive function (Montreal Cognitive Assessment (MoCA) and Cognitive Abilities Screening Instrument (CASI)) using linear regression analysis. Results A lower cognitive function was noted in hemodialysis patients compared to control subjects. The receptor activator of nuclear factor kappa-B ligand (RANKL) was the only bone marker found to be associated with cognitive function (MoCA and CASI tests) in hemodialysis patients without a prior stroke or dementia diagnosis. In stepwise multiple linear regression analysis, the association remained significant in MoCA (β = 1.14, 95% CI 0.17 to 2.11) and CASI (β = 3.06, 95% CI 0.24 to 5.88). Short-term memory (β = 0.52, 95% CI 0.01 to 1.02), mental manipulation (β = 0.51, 95% CI 0.05 to 0.96), and abstract thinking (β = 0.57, 95% CI 0.06 to 1.09) were the significant subdomains in the CASI score related to RANKL. Conclusions Serum RANKL levels were potentially associated with better cognitive function in hemodialysis patients. Further large-scale and prospective studies are needed to confirm our findings.

Highlights

  • Patients with end-stage kidney disease (ESKD) have a threefold dementia prevalence rate than the age-matched general population [1]

  • All neuropsychological test scores were lower in hemodialysis participants compared to the reference control subjects, except Center for Epidemiologic Studies Depression Scale (CES-D), Cognitive Abilities Screening Instrument (CASI) long-term memory domain, language domain, and name fluency domain

  • All serum biomarker levels were higher in hemodialysis participants compared to the reference control subjects, except Dickkopf-related protein 1 (DKK1) (Table 2)

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Summary

Introduction

Patients with end-stage kidney disease (ESKD) have a threefold dementia prevalence rate than the age-matched general population [1]. Several bone turnover markers were found to be associated with cognitive function in general population, such as Dickkopf-related protein 1 (DKK1) [11, 12], Osteocalcin (OC) [13, 14], Osteopontin (OPN) [15], Osteoprotegerin (OPG) [16], and Leptin [17]. The receptor activator of nuclear factor kappa-B ligand (RANKL) was the only bone marker found to be associated with cognitive function (MoCA and CASI tests) in hemodialysis patients without a prior stroke or dementia diagnosis. Further large-scale and prospective studies are needed to confirm our findings

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