Increased plasma urotensin-II and carotid atherosclerosis are associated with vascular dementia

Aim: Human urotensin-II (U II) is a cyclic neuropeptide with potent vasoconstrictive activity in the vasculature. The expression of U II and its receptor (UT) mRNA is detected at high levels in the brain. We evaluated the relationship between plasma U II levels and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Methods: Carotid artery intima-media thickness (IMT), plaques, plasma levels of immunoreactive U II (IR-U II), and atherosclerotic biomarkers were determined in 42 patients with VaD, 197 with Alzheimer's disease (AD), and 47 non-demented elderly controls. Results: Age, gender, body mass index, systolic blood pressure (SBP), fasting plasma glucose, insulin, triglycerides, high-density lipoprotein cholesterol, leptin, and plasminogen activator inhibitor-1 levels were not significantly different among these groups. IR-U II, low-density lipoprotein (LDL) cholesterol, lipoprotein(a), lipid peroxides, interleukin-6, and high-sensitive C-reactive protein (hs-CRP) levels, and maximum IMT were significantly higher in VaD than in AD patients or controls. IR-U II level showed a significantly positive correlation with SBP or maximum IMT. Multivariate logistic regression analysis revealed a significantly independent association between IR-U II levels or increased maximum IMT (≥1.1 mm) and VaD as compared with SBP, LDL cholesterol, and interleukin-6 levels. Conclusion: Increased plasma IR-U II levels and carotid atherosclerosis may be involved in the pathogenesis and progression of VaD.