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

AIM: Human urotensin-II (UII) is a cyclic neuropeptide with potent vasoconstrictive activity in the vasculature. The expression of UII and its receptor (UT) mRNA is detected at high levels in the brain. We evaluated the relationship between plasma UII 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 UII (IR-UII), 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-UII, 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-UII level showed a significantly positive correlation with SBP or maximum IMT. Multivariate logistic regression analysis revealed a significantly independent association between IR-UII levels or increased maximum IMT (> or =1.1 mm) and VaD as compared with SBP, LDL cholesterol, and interleukin-6 levels. CONCLUSION: Increased plasma IR-UII levels and carotid atherosclerosis may be involved in the pathogenesis and progression of VaD.

Impact of increased plasma serotonin levels and carotid atherosclerosis on vascular dementia.

Serotonin (5-HT), a potent vasoconstrictor in the large cerebral arteries, is considered to play a key role in atherothrombosis and to be implicated in ischemic cerebrovascular events followed by delayed neuronal death. The present study aims at evaluating the relationship between plasma levels of 5-HT and vascular dementia (VaD) caused by stroke or atherosclerotic small vessel disease. Carotid artery intima-media thickness (IMT), plaques, plasma 5-HT levels and atherosclerotic parameters were determined in 20 patients with VaD and 40 age-matched controls. Age, gender, body mass index, systolic and diastolic blood pressure, fasting plasma glucose levels and serum levels of insulin, triglycerides, high-density lipoprotein cholesterol, leptin, adiponectin and interleukin-6 and plasma levels of plasminogen activator inhibitor-1 were not significantly different between the two groups. Serum levels of insulin-like growth factor-1 (IGF-1) were significantly lower in VaD patients than in controls. Plasma 5-HT levels, serum levels of hepatocyte growth factor (HGF), low-density lipoprotein (LDL) cholesterol and high-sensitive C-reactive protein (hs-CRP), max IMT and plaque frequency were significantly greater in VaD patients than in controls. There was a significant positive correlation of max IMT with 5-HT or HGF levels. Multiple logistic regression analysis revealed that increased plasma levels of 5-HT and carotid plaque prevalence had significantly independent association with VaD as compared with serum levels of IGF-1, HGF, LDL cholesterol and hs-CRP. These results suggest that increased plasma levels of 5-HT and carotid atherosclerotic plaques may be involved in the pathogenesis and progression of VaD.

Relationship between serum insulin-like growth factor-1 levels and Alzheimer's disease and vascular dementia.

OBJECTIVES: To determine whether decreased serum insulin-like growth factor-1 (IGF-1) levels could be a risk factor for dementia in older people. DESIGN: Case control study. SETTING: Showa University Karasuyama Hospital, Tokyo, Japan. PARTICIPANTS: A total of 436 Japanese elderly subjects: 106 patients with Alzheimer's disease (AD), 103 patients with vascular dementia (VaD), and 227 age-matched controls without dementia. MEASUREMENTS: Serum concentrations of IGF-1 and atherogenic lipoproteins, carotid artery intima-media thickness (IMT), and plaques were determined. RESULTS: Mini-Mental State Examination (MMSE) scores were positively correlated with serum IGF-1 concentrations as well as mean blood pressure or body mass index and were negatively correlated with age, serum low-density lipoprotein cholesterol and lipoprotein(a) concentrations, and carotid IMT. Serum IGF-1 concentrations had a significant inverse correlation with carotid IMT. Analysis across the IGF-1 quartiles revealed a threshold effect of low IGF-1 on MMSE score in subjects with the IGF-1 levels of 140 ng/mL or less (50% percentile) versus those with IGF-1 levels greater than 140 ng/mL. Multiple logistic regression concerning AD and VaD retained serum IGF-1 concentrations of 140 ng/mL or less and carotid IMT of 0.9 mm or more. Patients with AD and VaD had significantly lower IGF-1 concentrations and greater mean IMT than nondemented controls. CONCLUSION: These results suggest that decreased serum IGF-1 level and the progression of carotid atherosclerosis could play a role as independent risk factors for dementia.

High prevalence of Chlamydia pneumoniae antibodies and increased high-sensitive C-reactive protein in patients with vascular dementia.

OBJECTIVES: To determine the relationships between Chlamydia pneumoniae infection, carotid atherosclerosis, and dyslipidemia in patients with vascular dementia (VaD) and Alzheimer's disease (AD). DESIGN: Case control study. SETTING: Showa University Karasuyama Hospital, Tokyo, Japan. PARTICIPANTS: One hundred twenty-four elderly subjects: 31 with VaD, 61 with AD, and 32 age-matched controls without dementia. MEASUREMENTS: Presence of antibodies to C. pneumoniae (immunoglobulin G (IgG) and IgA), the serum concentrations of high-sensitive C-reactive protein (hs-CRP) and atherogenic lipoproteins, and the carotid artery intima-media thickness (IMT) and plaques were determined. RESULTS: Age; body mass index; systolic and diastolic blood pressures; and fasting plasma glucose, hemoglobin A(1c), high-density lipoprotein cholesterol, and apolipoprotein A-I, B, and E concentrations did not differ significantly between the three groups, but the mean IMT and frequency of atherosclerotic plaques in the carotid arteries, as well as the serum concentrations of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a), and lipid peroxides were significantly greater in VaD patients than in AD patients or nondemented controls. Hs-CRP concentrations and prevalence of C. pneumoniae IgG and IgA antibodies also were significantly higher in VaD patients than in AD patients and nondemented controls. Multiple logistic regression analysis revealed that carotid IMT and plaques, LDL-C, lipid peroxides, hs-CRP, and IgG and IgA C. pneumoniae seropositivity were independent risk factors for VaD. CONCLUSION: These results suggest that carotid atherosclerosis, atherogenic lipoproteins, and C. pneumoniae infection (as documented by the IgG and IgA seropositivity together with increased hs-CRP) may be VaD risk factors.

Influence of insulin-like growth factor-1 and hepatocyte growth factor on carotid atherosclerosis and cognitive function in the elderly.

OBJECTIVE: This study investigated the relationship between serum levels of two neurotrophic factors, insulin-like growth factor-1 (IGF-1) and hepatocyte growth factor (HGF), and carotid atherosclerosis and cognitive function in the elderly. METHODS: Serum levels of IGF-1 and HGF, carotid artery intima-media thickness (IMT), and Mini-Mental State Examination (MMSE) scores were determined in 60 subjects over 65 years old (35 patients with vascular dementia and 25 without dementia). RESULTS: In all subjects IGF-1 levels showed a significant positive correlation with the MMSE score (r = 0.262, p = 0.0427) and a negative correlation with the IMT (r = -0.284, p = 0.0277) and the HGF level (r = -0.422, p = 0.0007). HGF levels were significantly correlated with IMT (r = 0.259, p = 0.0455) and lipoprotein(a) levels (r = 0.279, p = 0.0372). Mean MMSE scores and IGF-1 levels were significantly lower in patients with vascular dementia than in the non-demented controls. Mean IMT and the frequency of atherosclerotic plaque in the carotid arteries as well as the serum levels of HGF, LDL cholesterol, lipoprotein(a) and lipid peroxides were significantly increased in the demented patients compared with the non-demented controls. CONCLUSION: A decrease of IGF-1 along with an increase of HGF may reflect an underlying biological process that influences cognitive decline as well as carotid atherosclerosis in the elderly.

Small dense low-density lipoprotein and carotid atherosclerosis in relation to vascular dementia.

Vascular dementia (VaD) and Alzheimer's disease (AD) are the most common causes of dementia in the elderly. The aim of this study was to investigate carotid atherosclerosis, serum lipid profiles, and atherogenic hormone levels in nondiabetic Japanese men with VaD or AD. Carotid artery intima-media thickness (IMT) and plaque, serum lipid and lipoprotein profiles, including low-density lipoprotein (LDL) particle size, as well as insulin-like growth factor-I (IGF-I, somatomedin C) and testosterone levels, were determined in 34 patients with AD, 37 patients with VaD, and 63 healthy male controls. Age, body mass index, systolic and diastolic blood pressure, and fasting plasma glucose, hemoglobin A(1c) (HbA(1c)), triglyceride, high-density lipoprotein (HDL)-cholesterol, and apolipoproteins (apo) A-I, B, and E levels did not differ significantly among the 3 groups. However, the mean value of carotid IMT, the frequency of atherosclerotic plaque deposition, the serum levels of LDL-cholesterol, lipoprotein(a), and lipid peroxides, and the incidence of small dense LDL (particle diameter