The U-shaped association between serum direct bilirubin and incident mild cognitive impairment in hemodialysis patients: a multicenter study

Previous studies have suggested an association between low serum bilirubin concentrations and increased risk of cognitive impairment. This study aimed to explore the association and dose-response relationship between serum direct bilirubin (DBIL) concentrations and mild cognitive impairment (MCI) among hemodialysis patients.

This is a multicenter cross-sectional study with patients undergoing hemodialysis from 22 dialysis centers in Guizhou Province, China. The outcome was mild cognitive impairment (MCI), measured with a Mini-Mental State Examination. The association and dose-response relationship between serum DBIL and MCI incidence were examined using multivariate logistic regression analysis, restricted cubic spline, and subgroup analysis to explore the association of serum DBIL concentrations with MCI.

Of the 4223 enrolled patients (mean age 55.2 ± 15.3 years, 60.4% males), 1187 (28.1%) had MCI. Serum DBIL of 0.10-1.67umol/L [multivariable-adjusted odds ratios (OR) 1.32, 95% confidence interval (CI): 1.08–1.60, P = 0.005], 2.31-3.20umol/L (OR = 1.22, 95%CI: 1.00-1.49, P = 0.047), and > 3.21umol/L (OR = 1.32, 95%CI: 1.08–1.61, P = 0.006) had increased risk of MCI compared with 1.68-2.30umol/L. The dose-response analysis between serum DBIL and MCI showed a U-shaped relationship (P for non-linearity = 0.009), and the serum DBIL concentrations with the lowest risk of MCI was 2.01umol/L. As the serum DBIL concentrations were lower than the reference, the risk of MCI decreased by 49% per standard deviation (SD) increase in serum DBIL (OR = 0.51, 95%CI: 0.29–0.89, P < 0.001); when the concentration exceeds 2.01umol/L, a rise per SD increased the risk of MCI by 9% (OR = 1.09, 95%CI:1.01–1.17, P < 0.001).

Our findings suggest a U-shaped association between serum DBIL and MCI among hemodialysis patients.