[Effects of Tongluo Xingnao effervescent tablets on blood rheology, iNOS, VEGF and LDH-5 in MID rats].

The study was to explore effects of Tongluo Xingnao effervescent tablets on the blood rheology, iNOS, VEGF and LDH-5 in multi-infarct dementia(MID) model rats. Establish MID model rats were induced by microthrombosis, from which 50 successful model rats were randomly divided into five groups, such as the model control group, the dihydroergotoxine mesylate tablets(hydergine) group(0.7 mg•kg⁻¹), Tongluo Xingnao effervescent tablets high-dose, medium-dose and low-dose groups(7.56, 3.78, 1.89 g•kg⁻¹). Another ten rats in the sham group were randomly selected as the parallel control group. Each group was orally administered with drugs for 90 days. The learning and memory ability was evaluated with the Morris water maze test, while the whole blood viscosity and the erythrocyte aggregation index derived from abdominal aorta were measured in different shear rates. In addition, the levels of VEGF and iNOS in the serum were determined by ELISA kits. The expression of LDH-5 in hippocampus of rats was measured with immunohistochemistry and image quantitative analysis. The result showed that Tongluo Xingnao effervescent tablets notably decreased the escape latency of MID model rats, increased times of entering into the escape platform and prolonged retention time in medium ring, meanwhile the whole blood viscosity in MID model rats was also notably reduced in four shear rates, i.e. 1, 5, 30, 200 S⁻¹, erythrocyte aggregation index, serum VEGF and iNOS, and average optical density value of LDH-5, with a statistically significant differences compared with the model control group (P<0.05). In conclusion, Tongluo Xingnao effervescent tablets could improve the ability of learning and memory of MID model rats and the blood rheology, reduce the level of iNOS, VEGF and the expression of LDH-5, and then improved the brain energy supply.

Vascular and biochemical risk factors of vascular dementia after lacunar strokes (S-VaD) and after multiinfarcts in strategic areas (M-VaD).

Vascular cognitive impairment is an important cause of cognitive decline in the elderly. Ischemic lesions in the brain have an influence on the natural history of dementia. Vascular dementia can be caused by small-vessels disease (S-VaD) or by large-artery atherosclerosis with vascular lesions in strategic areas of the brain (M-VaD). In both cases changes in white matter are observed. In 60 patients with S-VaD and in 34 with M-VaD the presence of vascular and biochemical risk factors was evaluated and compared to age and sex matched 126 controls without dementia. Coronary artery disease, atrial fibrillation, hypertension and strokes were observed more frequently in both investigated groups. Of biochemical risk factors, hyperhomocysteinemia (associated with low levels of folic acid and vitamin B 12) and low HDL cholesterol levels were found in both forms of VaD.

Effects of acupuncture on hemorheology, blood lipid content and nail fold microcirculation in multiple infarct dementia patients.

Forty-six cases of multiple infarct dementia (MID) in the treatment group were treated by acupuncture with the principle of supplementing the inferiority to clear the superiority and regulating spirit to invigorate intelligence. Changes of the blood lipid content, hemorheological indexes and nail fold microcirculation in the treatment group were compared with those in the randomly assigned control group. The data collected showed that the changes in the treatment group were remarkable, and part of them were superior to their counterparts obtained in the control group by statistical analysis. It is indicated that acupuncture can effectively regulate the affected hemodynamic state in MID.

Peripheral inflammatory response in Alzheimer's disease and multiinfarct dementia.

Whether peripheral inflammatory molecules can be considered markers of dementia is still an open issue. We have investigated the presence of circulating cytokines and the ability of blood cells to release them in response to an inflammatory stimulus in patients with different types of dementia and in age-matched controls. A significant increase in circulating interleukin-1beta in moderate Alzheimer and in multiinfarct (145 and 224 times control concentration, respectively) dementia and in circulating tumor necrosis factor-alpha concentration in multiinfarct dementia patient group (156%) were found. Tumor necrosis factor-alpha and interleukin-6 released from blood cells after exposure to lipopolysaccharide were significantly reduced in moderate Alzheimer (60%, both cytokines) and multiinfarct patients (71 and 50%, respectively), while interleukin-10 was decreased only in multiinfarct patients (61%). The results show that patients with Alzheimer disease or multiinfarct dementia have an upregulation of circulating cytokines and a downregulation of cytokines released by blood cells.

Asymptomatic cores and paracrystalline mitochondrial inclusions in CADASIL.

Three siblings with genetically assessed cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with core-like lesions and mitochondrial abnormalities in muscles are described. Involvement of the Ryanodine receptor 1 gene was excluded. In the current cases, the relation between molecular genetic lesion and muscle fiber abnormalities remains to be determined, but the Notch3 gene may influence mitochondrial metabolism.

Inflammatory markers in Alzheimer's disease and multi-infarct dementia.

Inflammation has been involved in the pathogenesis of dementia. The study evaluates the presence and the source of pro- and anti- inflammatory cytokines in the blood of patients with Alzheimer's disease (AD), multi-infarct dementia (MID) or in non-demented elderly people (controls). Tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, IL-10, IL-1 receptor antagonist (IL-1Ra) and soluble TNF receptor I (sTNF-RI) plasma concentrations and release from blood cells stimulated with lipopolysaccharide (LPS, 1 microg/ml) were determined. The results show that TNF-alpha released from blood cells is significantly decreased (27%) in all demented patients compared to controls. Circulating TNF-alpha is increased (400%) only in MID patients. In these patients plasma levels of sTNF-RI are increased (53%) and IL-10 from stimulated blood cells decreased (47%) compared to non-demented subjects. The results show that: (1) peripheral production of TNF-alpha is blunted in demented (both AD and MID) patients compared to non-demented age-matched subjects; (2) AD patients have a selective disregulation of the peripheral TNF-alpha system; (3) different cytokines are up- or down- regulated in MID patients showing that in this condition the pro- and anti-inflammatory peripheral cytokine system is more widely affected.

[Serum apolipoprotein A I, B100 and E levels and apolipoprotein E polymorphism in patients with Alzheimer's disease and multiple infarction dementia in Chinese population].

OBJECTIVE: To investigate the relationship of serum apolipoprotein (apo) A I, B100 and E levels and apo E polymorphism to Alzheimer's disease (AD) and multiple infarction dementia (MID) in Chinese population. METHODS: The apoE phenotypes were assayed by isoelectric focusing and immunoblotting, and apolipoproteins were determined by radial immunodiffusion assay in 75 patients with AD, 36 patients with MID and 60 control subjects. RESULTS: The frequency of apo E4 allele (epsilon 4) was significantly higher and the frequency of epsilon 2 allele was lower in AD group, compared with those in the control group (0.2333 vs 0.0666, 0.0467 vs 0.0833, P < 0.05). The frequency of epsilon 4 allele in MID group was also higher than that in the control group (0.2083 vs 0.0666, P < 0.05). The fasting serum apoA 1 and E levels in AD and MID groups were remarkably lower than those in the control group (P < 0.001 and P < 0.05). CONCLUSION: Apo E4 allele epsilon 4 was associated with AD and MID. ApoE4 might be a risk factor for AD and MID, and apo E2 might be a protective factor for AD. The serum apo A I and apoE levels were significantly decreased in patients with Alzheimer's disease and multiple infarction dementia.

A promising approach to the treatment of multi-infarct dementia.

Cerebrovascular multi-infarct dementia (MID) is associated with high fibrinogen levels and lipid fractions leading to an increase of both plasma and whole blood viscosity as well as raised aggregability of blood cells. One important goal in the treatment of MID therefore should be to reduce fibrinogen and lipoproteins and thereby to improve the Hemorheological State. The effect of heparin-induced extracorporeal LDL/fibrinogen precipitation (HELP), a method for safe and immediate reduction of parameters relevant to hemorheology, such as plasma fibrinogen and the lipoproteins, was investigated in 141 patients with MID. All the patients underwent two HELP applications within 8 days. The impact of HELP on MID was studied by changes of laboratory data and by evaluation of clinical symptoms before and after treatment. Each HELP session caused an immediate, safe and significant reduction of important rheological parameters such as fibrinogen, whole blood viscosity at high and low shear rate, plasma viscosity and red cell transit time. Also total cholesterol and low-density lipoprotein, lipoprotein(a) and the triglycerides had been reduced significantly. The results in laboratory measurement were followed by a statistically significant improved neurologic recovery, represented in the values of the Mathew Scale, the Mini Mental State Examination and the Activities-of-Daily-Living-Test. These results can indicate the importance and influence of hemorheology on clinical symptoms in MID.

Partial characterization of apoptotic factor in Alzheimer plasma.

We have previously demonstrated that a plasma natriuretic factor is present in Alzheimer's disease (AD), but not in multi-infarct dementia (MID) or normal controls (C). We postulated that the natriuretic factor might induce the increased cytosolic calcium reported in AD by inhibiting the sodium-calcium antiporter, thereby activating the apoptotic pathway. To test for a factor in AD plasma that induces apoptosis, we exposed nonconfluent cultured LLC-PK1 cells to plasma from AD, MID, and C for 2 h and performed a terminal transferase-dUTP-nick-end labeling (TUNEL) assay. The plasma from AD increased apoptosis nearly fourfold compared with MID and C. The effect was dose dependent and the peak effect was attained after a 2-h exposure. Additionally, apoptotic morphology was detected by electron microscopy, and internucleosomal DNA cleavage was found. We inhibited apoptosis by removing calcium from the medium, inhibiting protein synthesis with cycloheximide, alternately boiling or freezing and thawing the plasma, and digesting a partially purified fraction with trypsin. Heating AD plasma to 56 degrees C did not deactivate the apoptotic factor. These results demonstrate the presence of an apoptotic factor in the plasma of patients with AD.

Effects of antithrombin on Binswanger's disease with antiphospholipid antibody syndrome.

The authors present a family with Binswanger's disease (BD) and antiphospholipid antibody syndrome (APAS). In one patient from this family, lupus anticoagulant and high levels of hemostatic markers were detected. The presence of BD and the clinicobiological improvements observed after antithrombin treatment in this patient are peculiar to this familial case of APAS.

[Changes of erythrocyte and platelet membrane lipid pattern in different subtypes of dementia].

OBJECTIVE: To investigate the changes of platelet and erythrocyte membrane lipids and phospholipid composition in different types of dementia. METHODS: There were 19 patients with Alzheimer's disease, 25 patients with Binswanger's disease, 23 patients with multi-infarct dementia, 11 patients with single cortical infarct dementia, 7 patients with vascular dementia of haemodynamic type, 18 patients with dementia following Parkinson's disease, and 25 senile controls. Platelet and erythrocyte membrane cholesterol, total phospholipids and individual phospholipids were quantified. RESULTS: When compared with senile controls, the decrease of total phospholipids, phosphatidylcholine and phosphatidylethanolamine and the increase of cholesterol and cholesterol/total phospholipids ratio on the erythrocyte and platelet membrane were found in patients with Binswanger's disease and in those with multi-infarct dementia. The increase of erythrocyte and platelet membrane cholesterol, cholesterol/phospholipids ratio was found, but there was no significant change in membrane total phospholipids and phospholipid composition in patients with single cortical infarct dementia. CONCLUSION: Metabolic disorders of platelet and erythrocyte membrane phospholipids were noted in patients with Binswanger's disease. These disorders were related to white matter low attenuation.

Erythrocyte aging characteristics in elderly individuals with beginning dementia.

An increase in erythrocyte-bound IgG and enhanced breakdown of the erythrocyte anion exchanger band 3, characteristics of normal erythrocyte aging are observed in old, healthy individuals when compared with young donors. These findings indicate that the rate of cellular aging increases with organismal aging. Results from previous studies on the same parameters have suggested that the erythrocyte aging process is disturbed in patients in advanced stages of Alzheimer type dementia, and in individuals with Down's syndrome who show no signs of dementia. In this study we find no changes in erythrocyte aging parameters in old individuals in beginning stages of dementia of various etiologies. We conclude that, in general, characteristics of disturbed erythrocyte aging cannot serve as presymptomatic markers of Alzheimer-type dementia.

Apolipoprotein E genotypes and serum lipid levels in Alzheimer's disease and multi-infarct dementia.

OBJECTIVE: Assessment of apolipoprotein E genotype, serum cholesterol, triglycerides, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol levels in different types of dementia. SUBJECTS: 102 consecutive referrals to an old age psychiatry service based at Manchester were classified according to clinical criteria based on ICD 10. RESULTS: Thirty-seven were considered to have Alzheimer's disease, 16 multi-infarct dementia and 33 to be free from dementia. Sixteen patients, in whom a definitive diagnosis could not be reached or sufficient information was not available, were excluded from the study. There was an increase in the prevalence of the Apo E4 allele in both Alzheimer's disease (chi 2 = 3.82, p < 0.05) and multi-infarct dementia (chi 2 = 1.93, p < 0. = 0.16) by Wald tests compared to individuals without dementia. The increased prevalence of the E4 Allele in multi-infarct dementia was not related to serum lipid levels. CONCLUSION: The hypothesis that the onset of multi-infarct dementia may be precipitated by E4's mediation of higher serum cholesterol levels is not supported by the present study.

[Lipoprotein (a) and plasminogen in atherosclerosis]. / Lipoproteina (a) e plasminogeno nella malattia aterosclerotica.

The aim of this study was to evaluate plasma levels of lipoprotein (a) [LP(a)] and plasminogen in patients affected with atherosclerotic disease and to understand the mutual relationships. Eighty-four patients affected with atherosclerosis were examined and divided as follows: group I, 24 patients with peripheral arteriopathy; group II, 40 patients with ischemic heart disease (myocardial infarction and/or angina pectoris); group III, 20 patients with multi-infarct dementia; group IV (control group) with 20 healthy young subjects. The results show that Lp(a) plasma levels, in atherosclerotic patients, are higher than 30 mg/dl, while the plasminogen levels are lower than 80 mg/dl. There is an inverse correlation between these two data. Moreover, a different behaviour of Lp(a) and plasminogen rate related to age of patients, to number of atherosclerotic lesions or to acuteness of ischemic heart disease, was observed.

Binding of platelet-activating factor to platelets of Alzheimer's disease and multiinfarct dementia patients.

The binding of 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet-activating factor, PAF) to platelets was studied in 22 patients with probable Alzheimer's disease (AD), 11 with multi-infarct dementia (MID), 22 age-matched normal old controls, and 20 young subjects. The results showed a significantly lower degree of PAF binding to platelets of AD and MID patients than in those of the old controls and young subjects (133.3 +/- 8.5, and 123.4 +/- 16.5 vs. 202.3 +/- 11.6 and 206.7 +/- 17.3 receptors/cell, respectively; p < 0.01). These differences were due to reduced Bmax, while Kd remained unchanged. No significant difference was observed between the PAF binding to platelets of AD and MID patients nor between that of old and young controls. No correlation was found between age and binding in the various elderly groups. However, a significant correlation was found between PAF binding and degree of cognitive impairment in the AD patients. This is the first evidence to support a possible involvement of PAF in dementing disorders.

Amino acid concentration in dementia of the Alzheimer type and multi-infarct dementia.

Amino acids were measured in nine cases of dementia of the Alzheimer type, 10 cases of multi-infarct dementia, and 10 healthy controls. The severity of dementia was examined using mini-mental state test (MMST). Amino acid analysis (41 kinds) in the cerebrospinal fluid (CSF) and serum was performed in the Special Reference Laboratories. In the dementia of the Alzheimer type group, methionine and alanine concentrations in the CSF were significantly increased, and the CSF/serum ratios for both the alanine and glycine concentrations were significantly increased, in comparison with the healthy control group. In the multi-infarct dementia group, glycine, methionine, threonine, phenylalanine, and citrulline concentrations in the CSF were all higher than in the healthy control group. Significant negative correlations were found between the MMST score and the alanine, urea, arginine, and alpha-aminobutyric acid concentrations in the CSF. The number of amino acids which exhibited abnormality in dementia of the Alzheimer type and multi-infarct dementia was greater in the present study than in previous reports.

[Lipid metabolism parameters in patients with multi-infarct dementia and Alzheimer's type dementia]. / Parametry gospodarki lipidowej u pacjentów z otepieniem naczyniopochodnym i otepieniem typu alzheimerowskiego.

The concentrations were determined of triglycerides (TG), total cholesterol (Ch), high density fraction of (HDL-Ch), low density fraction of cholesterol (LDL-Ch), apolipoprotein B (apo-B) in patients with dementia of Alzheimer type (DAT, 14 patients) and multi-infarct dementia (MID, 63 patients). No significant differences in the estimated lipid parameters in both groups were found, except the calculated value of atherogenic index (Ch/HDL-Ch), which was significantly higher in patients with MID. Our results suggest that this parameter is a much more sensitive atherogenic indicator in blood-vessels than other tested lipid parameters. This finding may influence the therapeutic approach to patients with dementia.

Autoantibody reactivity in serum of patients with Alzheimer's disease and other age-related dementias.

Serum antibodies against a series of antigens, including an organ-specific central nervous system (CNS) antigen and the neurotransmitter serotonin, were investigated in 22 patients with Alzheimer's Disease (n=15) and other age-related dementias (n=7) by indirect immunofluorescence assay and enzyme-linked immunosorbent assay. Patients with dementia showed an increase of antibody-positive sera against nuclear antigen, gastric parietal cells, CNS antigen, gangliosides (Gm1), laminin, and keratin. Alzheimer's Disease patients alone exhibited antibodies against CNS antigen. However, the results do not show sufficient specificity and sensitivity for use as a diagnostic indicator.

Searching for a marker for Alzheimer's disease-Apo-E.

The authors present their study of 10 patients affected by Alzheimer's disease and 10 patients with multinfarctual dementia, who are already part of a CNR study, senile dementia project, longitudinal study. The method adopted was that of DNA crossbreeding and amplification, so as to have a precise individualisation of alleles APo-E, Apo E-3, Apo E-4 and of their various phenotype combinations. These isoforms are evaluated and compared with the disease studied, in order to help to identify a timely-marker for senile dementia. On the results obtained we hypothesised an association between Apo E-4 and the disease of about 40% for Alzheimer's disease, which leads us to increase our number of cases, regarding associations between demential diseases either Alzheimer or vascular and the presence of Apo E-4.