Abstract

This study aimed to detect associations of bile acid profile with white matter hyperintensity and quantify the risk of cerebral small vessel disease with high level of bile acid among cognitively normal individuals. All data were obtained from the patients with Alzheimer’s disease neuroimaging initiative with a 10 y follow-up. Multivariate linear regressions were performed with variable selection using the least absolute shrinkage and selection operator method and the linear mixed model was used to analyze longitudinal relationship between non-zero coefficient variables and white matter hyperintensity volume. Four predictors (age, deoxycholic acid, glucose, total intracranial volume) were identified by least absolute shrinkage and selection operator regression analysis and multivariate linear regressions. Age (p value<0.001, mean difference, 1.03 cm³ [95 % interval: 1.02, 1.04]) and deoxycholic acid (p value<0.05, mean difference, 1.05 cm³ [95 % confidence interval: 1.00, 1.10]) were significantly associated with white matter hyperintensity. When divided into two groups by the median deoxycholic acid level (1.38 μM), participants with higher deoxycholic acid levels had a higher white matter hyperintensity volume at the 4^th y than those with lower deoxycholic acid levels (mean difference, 0.1 points [95 % confidence interval: -0.17, -0.03]; p<0.05). We found that increased deoxycholic acid levels may lead to the progression of white matter hyperintensity, which suggest that higher deoxycholic acid burden may play a possible role in the pathogenesis of cerebral small vessel disease in cognitively normal older adults. Besides, the study indicates a possible role for inflammation in the pathogenesis of cerebral small vessel disease.