Low Bilirubin Levels Indicate a High Risk of Cerebral Deep White Matter Lesions in Apparently Healthy Subjects

Recent studies have reported that deep white matter lesions (DWMLs) on magnetic resonance imaging scans are related to the risk of developing impaired cognitive function in future. Bilirubin exhibits a potent antioxidant effect and an inverse relationship has been reported between bilirubin levels and the risk of several atherosclerotic diseases; however, there is limited evidence with regard to the effect of bilirubin levels on cerebrovascular diseases including DWMLs. This cross-sectional study included 1121 apparently healthy Japanese adults. The subjects were divided into three groups according to their bilirubin levels (low, <0.5 mg/dl; intermediate, >= 0.5 mg/dl and <1.0 mg/dl; and high, >= 1.0 mg/dl). The severity of DWMLs was evaluated according to Fazekas scale and their relation to bilirubin levels was examined. The association between bilirubin levels and the presence of severe DWMLs was assessed using multivariate logistic regression analysis. The analysis revealed that the low- and intermediate bilirubin groups indicated 2.36- and 1.33-fold increase in the prevalence of severe DWMLs compared with the high-bilirubin group, respectively (95% confidence interval (CI): 1.12-4.97 (the low-bilirubin group), 95%CI: 0.85-2.07 (the intermediate-bilirubin group). In conclusion, low total bilirubin levels could be associated with a high prevalence of severe DWMLs in apparent healthy subjects.