The effect of scalp electroacupuncture combined with Memantine in patients with vascular dementia: A retrospective study.

Currently there is no effective treatment for vascular dementia (VaD). Pharmacological treatment often lead to severe complications and require drug dosage adjustment. This study investigated the effect of scalp electroacupuncture combined with Memantine in VaD. The safety and antioxidative effect of scalp electroacupuncture were also explored.A retrospective study was conducted and data of inpatients of Linyi Central Hospital with VaD between June 2017 and May 2018 were collected and sorted. The patients were divided into scalp electroacupuncture-medication (A), scalp electroacupuncture (B) and medication (control) (C) groups, in which Memantine was prescribed as medication. Cognitive function, activities of daily living and quality of life assessed by Montreal Cognitive Assessment (MoCA), Barthel index and dementia quality of life questionnaire; the contents of superoxide dismutase, lipid peroxide and nitric oxide in blood samples; and adverse reaction were compared.Data from a total of 150 patients were collected (Group A, n = 55; Group B, n = 50; Group C, n = 45). The post-treatment/follow-up Montreal Cognitive Assessment, Barthel index and dementia quality of life questionnaire scores were significantly improved in all groups compared to pre-treatment (groups A and B, P<.01; group C, P<.05). The improvements were significant for groups A vs C, B vs C (P<0.01, both), and group A vs B (P<.05). The post-treatment/follow-up levels of lipid peroxide and nitric oxide decreased significantly while superoxide dismutase increased significantly in groups A and B compared to pre-treatment (P<.01, both). The differences were significant for groups A vs C, and B vs C (P < .01, both), but not significant between groups A and B (P > .05). There were no significant adverse events occurred during the study and follow-up.In combined treatment, scalp electroacupuncture works in parallel with Memantine and significantly increase the therapeutic effect in VaD with no significant adverse events. Scalp electroacupuncture may have the potential to serve as an option or alternative treatment for VaD. Scalp electroacupuncture may alleviate VaD symptoms through its antioxidative mechanism.

Ocimum Sanctum Linn: A Potential Adjunct Therapy for Hyperhomocysteinemia-Induced Vascular Dementia.

Vascular dementia (VaD) is well recognized as the second most familiar form of dementia in the aged population. The present study is aimed to investigate the neuroprotective effects of ethanolic extract of leaves of Ocimum sanctum (EEOS) against hyperhomocysteinemia (HHcy)-induced vascular dementia (VaD) in Wistar rats. HHcy was induced by administering L-methionine (1.7 g/kg, p.o) for 4 weeks. Donepezil (0.1 mg/kg, p.o.) and EEOS (100 mg/kg, 200 mg/kg, 400 mg/kg, p.o.) were administered from the 14th day of L-methionine treatment. The behavioral impairment caused due to HHcy in rats was assessed by the Morris water maze (MWM) and Y-maze tests using a video tracking system. Biochemical estimations and aortic ring assay were also performed followed by a molecular docking analysis of active chemical constituents present in the leaves of Ocimum sanctum Linn. In this study, the EEOS treatment in hyperhomocysteinemic rats has showed significant improvement in spatial learning and working memory performance. The EEOS treatment further increased nitric oxide bioavailability and significantly altered all serum and brain biochemical parameters in a dose-dependent manner. The docking analysis revealed that among all the phytoconstituents of Ocimum sanctum compound (IX), molludistin has showed good inhibitory activity against S-adenosyl homocysteine, thus preventing homocysteine formation and may be responsible for potential effects of EEOS against HHcy-induced VaD. From our results, we conclude that EEOS can be used as a promising adjunct therapy for treatment of HHcy-induced VaD and oxidative stress.

Preventative effects of alpha-naphtho flavone in vascular dementia.

Vascular dementia (VaD) refers to the loss of reasoning, planning, judgment, and memory as a result of reduced blood flow, inflammation, activation of immune cells, and neurodegenerative processes. Here, we tested the preventive effects of alpha-naphthoflavone (ANF) on a model of vascular dementia induced by four-vessel occlusion (4VO) in rats. Animals were treated orally for 5 consecutive days with 10 mg/kg of donepezil (a traditional therapeutic drug) and 40 and 80 mg/kg ANF. The treatment with ANF exerted effects that were similar to those induced by donepezil. This included prevention of cognitive impairment, alterations in the plasma levels of homocysteine and nitrate and the activity of acetylcholinesterase and myeloperoxidase and the tissue level of glutathione, and thiobarbituric acid reactive substances in the brain tissues. These findings suggest that herbal-derived ANF is as effective as traditional drugs in vascular dementia.

Protective Effect of Hyperbaric Oxygen Therapy on Cognitive Function in Patients with Vascular Dementia.

Recent studies have shown that hyperbaric oxygen (HBO) has a therapeutic effect on vascular dementia (VD); however, the exact mechanism remains unclear. This article aims to reveal the protective effects and underlying mechanisms of HBO on VD. A total of 158 patients with VD were prospectively included in the study and were randomly divided into control group and HBO group. The control group was given conventional treatment and the HBO group was treated with HBO in addition to conventional treatment. The following HBO protocol was practiced: 5 days per week, 60 min each, 100% oxygen at 2 standard atmospheric pressures for 12 weeks. The Mini-Mental State Examination (MMSE) scores and serum Humanin levels were detected before and after treatments in both groups. The baseline characteristics were not different dramatically between groups (p > 0.05). There was no significant difference in MMSE scores and serum Humanin levels between the two groups before treatment (p > 0.05). After treatment, compared with the control group, the MMSE scores and serum Humanin levels in the HBO group were significantly increased (p < 0.05). Spearman correlation analysis showed that the serum Humanin levels were positively correlated with MMSE scores (r = 0.409, p < 0.05) and this correlation was independent of baseline characteristics (ß = 0.312, p < 0.05). HBO therapy can improve cognitive function in patients with VD, and its mechanism may be related to elevated serum Humanin levels.

Comparative pharmacokinetic study of the components of Jia-Wei-Kai-Xin-San in normal and vascular dementia rats by ultra-fast liquid chromatography coupled with tandem mass spectrometry.

A fast, sensitive, and reliable ultra-high performance liquid chromatography coupled with tandem mass spectrometry method has been developed and validated for simultaneous quantification of geniposide, polygalaxanthone III, 3,6'-disinapoyl sucrose, α-asarone, ß-asarone, poricoic acid A, poricoic acid B, dehydrotumulosic acid, deoxyschizandrin, schizandrin B, and kaempferide in plasma after oral administration of extracts of Jia-Wei-Kai-Xin-San in normal and vascular dementia rats. The developed method was precise and accurate within the linearity range of the analytes. The lower limits of quantification were 1.04-2.68 ng/mL for all the analytes. Both intra- and inter day precision and accuracy of the analytes were all within accepted criteria. The mean extraction recoveries of the analytes and the internal standard from rat plasma were all >60.0%. The validated method had been successfully applied to compare pharmacokinetic profiles of the analytes in plasma of normal and vascular dementia rat treated with herbal extracts. Results indicated that differences existed between normal and vascular dementia model rats except dehydrotumulosic acid and kaempferide, which might be due to the pathology of vascular dementia and pharmacological effect of the analytes. These pharmacokinetic studies might benefit for the mechanism exploration and clinical use of traditional Chinese medicine formulae.

Serum phosphorus levels and risk of incident dementia.

Higher serum phosphorous is associated with cerebral small vessel disease, an important driver of cognitive decline and dementia. Whether serum phosphorous, a potentially modifiable parameter, associates with risk of incident dementia is not known. We aimed to examine the association between serum phosphorous and risk of incident dementia and to determine if the association is modified by age. We used the United States Department of Veterans Affairs national databases to build a longitudinal observational cohort of US veterans without prior history of dementia and with at least one outpatient serum phosphorus between October 2008 and September 2010 and followed them until September 2014. Serum phosphorus was categorized into quintiles: ≤2.9, >2.9 to ≤3.2, >3.2 to ≤3.5, >3.5 to ≤3.9, >3.9 mg/dL. There were 744,235 participants in the overall cohort. Over a median follow-up of 5.07 years (Interquartile range [IQR]: 4.28, 5.63), adjusted Cox models show that compared to quintile 2, the risk of incident dementia was increased in quintile 4 (Hazard Ratio [HR] = 1.05; CI = 1.01-1.10) and quintile 5 (HR = 1.14; CI = 1.09-1.20). In cohort participants ≤60 years old, the risk of incident dementia was increased in quintile 4 (HR = 1.29; CI = 1.12-1.49) and 5 (HR = 1.45; CI = 1.26-1.68). In participants > 60 years old, the risk was not significant in quintile 4, and was attenuated in quintile 5 (HR = 1.10; CI = 1.05-1.16). Formal interaction analyses showed that the association between phosphorous and dementia was more pronounced in those younger than 60, and attenuated in those older than 60 (P for interaction was 0.004 and <0.0001 in quintiles 4 and 5; respectively). We conclude that higher serum phosphorous is associated with increased risk of incident dementia. This association is stronger in younger cohort participants. The identification of serum phosphorous as a risk factor for incident dementia has public health relevance and might inform the design and implementation of risk reduction strategies.

Effects of in-vitro cultured calculus bovis on learning and memory impairments of hyperlipemia vascular dementia rats.

ETHNOPHARMACOLOGICAL RELEVANCE: In-vitro cultured calculus bovis (ICCB) is a quality substitute for natural bezoar which is used for the therapeutic purpose of treating encephalopathy. ICCB has been authorized to use on clinic. The aim of the study is to evaluate the effects and the potential mechanisms of in-vitro cultured calculus bovis (ICCB) on learning and memory impairments of hyperlipemia vascular dementia (HVD) rats. MATERIALS AND METHODS: The HVD model was established by permanent occlusion of bilateral common carotid arteries based on hyperlipemia rats. Learning and memory abilities were evaluated by morris water maze test and shuttle box test. Ultraviolet-visible spectrophotometry (UV-vis) was employed to determine the SOD, MDA and NO in cerebral tissue, as well as the TG in serum. HE staining and toluidine blue staining were employed to evaluate cone cells damage in hippocampus CA1. An immunohistochemistry was used to measure the Bax and Bcl-2 expressions in cerebral tissue. RESULTS: Compared with control group, the abilities of spatial learning and memory and conditional memory were decreased significantly in HVD group (P<0.01, P<0.05). MDA content in cerebral tissue was remarkably increased while the SOD activity and NO content were both decreased (P<0.01). TG content in serum was increased remarkably (P<0.01). And the cone cells in hippocampus CA1 were damaged obviously. Compared with HVD group, ICCB treatment improved the abilities of learning and memory, elevated the SOD activity (P<0.01, P<0.05), reduced the MDA content (P<0.01) as well as the TG content in serum (P<0.01), increased the NO content (P<0.01), improved the damaged cone cells in hippocampus CA1, increased the number of cones cells (P<0.01), decreased the Bax expression, and increased the Bcl-2 expression (P<0.01). CONCLUSION: ICCB could improve the abilities of learning and memory in HVD rats. It might be related to anti-oxidative, regulation of Bax and Bcl-2 expressions, and the alleviation of cone cells damage.

Effect of Sancaijiangtang on plasma nitric oxide and endothelin-1 levels in patients with type 2 diabetes mellitus and vascular dementia: a single-blind randomized controlled trial.

OBJECTIVE: To observe the effect of Sancaijiangtang powders on plasma nitric oxide and endothelin-1 levels. We sought to identify the common pathological link and mechanism of action for Traditional Chinese medicine in type 2 diabetes mellitus and vascular dementia, and to explicate the material basis for treating the different diseases with the same method in Traditional Chinese Medicine. METHODS: In total, 168 patients with type 2 diabetes mellitus and vascular dementia were enrolled in the study, and randomly divided into two groups by simple randomization. Patients in the treatment group received oral Sancaijiangtang powders with pioglitazone hydrochloride three times daily, while patients in the control group received pioglitazone hydrochloride alone. The treatment course was for 12 weeks. Mini-mental state examinations (Chinese version) and Montreal Cognitive Assessments (Beijing version) were performed, and fasting plasma glucose, fasting insulin, hemoglobin A1c, homeostasis model assessment of insulin resistance, plasma nitric oxide and endothelin-1 levels were measured before and after the treatment. RESULTS: The post-treatment levels for all measurements in both groups were better than pre-treat- ment levels (P < 0.05). The post-treatment levels for all measurements in the treatment group were better than the levels measured in the control group (P < 0.05). CONCLUSION: Type 2 diabetes mellitus and vascular dementia have common pathological mechanisms for insulin resistance and endothelium dysfunction. Sancaijiangtang powders could improve the release of nitric oxide and inhibit the secretion of endothelin-1. Therefore, the material basis exists for treating the different diseases with the same method in Traditional Chinese Medicine.

[The importance of folic acid deficiency in the pathogenesis of vascular, mixed and Alzheimer's disease dementia]. / Znaczenie niedoboru kwasu foliowego w patogenezie otepien typu alzheimerowskiego, naczyniopochodnego I mieszanego.

UNLABELLED: Alzheimer's disease (AD), vascular dementia (VaD) and mixed dementia (MD) are the most common dementia diseases among the elderly. Currently, there is no effective treatment of these diseases and, therefore, it seems justified to develop the principles of prevention, taking into account the elimination of risk factors. Among them folic acid deficiency may play an important role. THE AIM OF THE STUDY: To evaluate possible relationship of folate deficiency with the development of selected dementia diseases: vascular dementia (VaD), Alzheimer's disease (AD), mixed dementia (MD). MATERIAL AND METHODS: The study involved 166 people, including 47 people with the diagnosis of AD, 41 with VaD and 36 with MD. The control group consisted of 42 persons without cognitive impairment. All patients underwent a general physical, neurological, psychiatric and extensive neuropsychological examination, as well as routine blood and biochemical screening tests and neuroimaging. The level of serum folate (Fol) was measured by electrochemiluminescence immunoassay. To assess the correlation of Fol level with the cognitive impairment neuropsychometric scales: Mini Mental State Examination (MMSE) and Clinical Dementia Rating (CDR) were used. RESULTS: In patients with dementia, compared with the control group, there were significantly lower levels of folic acid (p = 0.04). There was no difference in the concentration of Fol in groups of patients (p = 0.0889). In people without cognitive impairment (CDR 0) levels of folic acid were significantly higher compared to the group with moderate dementia (CDR 2, p = 0.0475). CONCLUSIONS: The results may suggest that folic acid deficiency is one of the possible causes of dementia, but does not determine its type. Determination of serum Fol in the elderly and supplementation of this vitamin deficiency may play an important role in the prevention of the most common dementias.

Long-term treatment with standardized Ginkgo biloba extract (EGb 761) attenuates cognitive deficits and hippocampal neuron loss in a gerbil model of vascular dementia.

The standardized extract of Ginkgo biloba EGb 761 has been used to reduce cognitive dysfunction. The present study was designed to evaluate the effect of postischemic oral treatment with EGb 761 in a model of vascular dementia in gerbils. Daily oral posttreatment with EGb 761 led to a significant recovery of spatial memory assessed by the object location test, inhibited the decrease in plasma SOD activity and protected the hippocampal CA1 neurons, even when administered after the insult. These data provide further evidence for the therapeutic potential of EGb 761 in the treatment of vascular dementia.

A randomized placebo controlled trial of homocysteine lowering to reduce cognitive decline in older demented people.

INTRODUCTION: Whether homocysteine lowering by B vitamins can reduce cognitive decline in Alzheimer disease and vascular dementia patients is unclear. METHODS AND MATERIALS: 140 subjects with mild to moderate Alzheimer disease or vascular dementia were randomly assigned to take 1 mg of methylcobalamin and 5 mg of folic acid, or placebo once daily for 24 months. The primary outcome was Mattis dementia rating scale (MDRS). Secondary outcomes were MDRS domain scores, neuropsychiatric inventory and Cornell scale for depression in dementia. Measurements were performed at baseline and every six months during the study. Fasting plasma tHCY concentrations were measured at baseline and month 18. RESULTS: Trial groups were well matched in baseline characteristics. The average plasma tHCY concentration of subjects was 14.1 ± 3.8 µmol/L. 80% of subjects completed the trial. The supplement group had average plasma tHCY reduced to 9.3 ± 2.7 µmol/L. There was no significant group difference in changes in any of the neuropsychological scores, but among those with elevated plasma tHCY (>13 µmol/L), the decline in MDRS (construction domain) was significantly smaller in the supplement group (median 0 versus 2 points in placebo group, P = 0.003). CONCLUSION: Homocysteine lowering in dementia patients did not significantly reduce global cognitive decline.

Comparative pharmacokinetics of paeoniflorin in plasma of vascular dementia and normal rats orally administrated with Danggui-Shaoyao-San or pure paeoniflorin.

Danggui-Shaoyao-San (DSS), a traditional Chinese medicinal prescription, is clinically used for the treatment of vascular dementia (VD). This study compared the pharmacokinetics of paeoniflorin, the main active ingredients in Paeonia lactiflora Pall, in VD and normal rats administrated with DSS or pure paeoniflorin. The absorptions of paeoniflorin in both VD and normal group of rats were better when orally administrated with DSS than that with pure paeoniflorin, which justified the combined use as formula DSS. Moreover, a better absorption of paeoniflorin in rats of the VD than in normal group was observed, which is helpful for the treatment of VD.

[Effect of kangxin capsule on homocysteine and beta-amyloid protein in vascular dementia patients].

OBJECTIVE: To observe the effect of Kangxin capsule (KXC) on homocysteine (HCY) and beta-amyloid protein (beta-Ap) in patients with vascular dementia. METHODS: Sixty-three patients with vascular dementia were randomly divided into two groups, the 33 patients in the treated group and the 30 in the control group. Basal treatment were given to both groups, besides, KXC was given to the treated group and Hydergine was given to the control group. The levels of plasma HCY, beta-Ap as well as the changes of mini mental state examination (MMSE), activity of daily living (ADL) and TCM Syndrome scoring were observed before and after treatment. RESULTS: KXC could significantly decrease the levels of HCY and beta-Ap (P < 0.01), rise the MMSE scores, reduce ADL scores and ameliorate TCM Syndrome. CONCLUSION: KXC can effectively regulate the levels of HCY, beta-Ap in vascular dementia patients.

The methionine-homocysteine cycle and its effects on cognitive diseases.

Homocysteine, a sulfur-containing amino acid, is a metabolite of the essential amino acid methionine, and exists at a critical biochemical intersection in the methionine cycle - between S-adenosylmethionine, the indispensable ubiquitous methyl donor, and vitamins B12 and folic acid. High blood levels of homocysteine signal a breakdown in this vital process, resulting in far-reaching biochemical and life consequences. The link between homocysteine and cardiovascular disease is well established, and decreasing plasma total homocysteine by providing nutritional cofactors for its metabolism has been shown to reduce the risk of cardiovascular events. Information has been emerging regarding a connection between homocysteine metabolism and cognitive function, from mild cognitive decline (age-related memory loss) to vascular dementia and Alzheimer's disease. Significant deficiencies in the homocysteine re-methylation cofactors cobalamin (B12) and folate, as well as the trans-sulfuration cofactor vitamin B6, are commonly seen in the elderly population, with a resultant increase in homocysteine with advancing age. Hyperhomocysteinemia has been shown to be an independent risk factor for cognitive dysfunction. Indirect and direct vascular damage can be caused by homocysteine, which has been implicated in vascular dementia, with an increased risk of multiple brain infarcts and dementia as homocysteine levels rise. A significant correlation has been found between risk of Alzheimer's disease and high plasma levels of homocysteine, as well as low levels of folic acid, and vitamins B6 and B12. All of these disease associations are thought to be interrelated via increased homocysteine and S-adenosylhomocysteine and subsequent hypomethylation of numerous substances, including DNA and proteins, that render vascular structures and neurons more susceptible to damage and apoptosis. Providing the nutritional cofactors for proper functioning of the methionine cycle may improve methylation and protect the brain from damage. Further studies need to be performed to assess whether this will also reduce the risk of cognitive diseases and/or improve cognitive functioning.

[Clinical study of effect of tianzhi granule on senile vascular demetia].

OBJECTIVE: To investigate the clinical effect of Tianzhi Granule (TZK) on senile vascular dementia (VaD), which is classified as sthenia of liver-yang. METHOD: Two hundred VaD patients were treated with TZK (0.5 g/bag), which was taken one bag each, three times a day. The treatment course was one month and they were treated for rwo courses. RESULT: TZK could remarkably increase gnosia and activity, with no striking difference from that of positive control group (P > 0.05). Simultaneously, TZK could significantly improve the clinical syndrome of traditional Chinese medicine and viability. It could also drastically reduce the whole blood and plasma viscosity and improve erythrodegeneration and abnormality of aggregation index in the abnormal blood viscosity patients. CONCLUSION: TMC has certain effects on senile VaD.

Is hyperhomocysteinemia due to the oxidative depletion of folate rather than to insufficient dietary intake?

Hyperhomocysteinemia is considered as a risk factor for cardiovascular diseases. Usually, an inverse relationship exists between homocysteine and folate levels, and supplementation with folate lowers homocysteine concentrations in patients. Therefore, hyperhomocysteinemia is mainly ascribed to the insufficient dietary intake of folate. Hyperhomocysteinemia has also been observed in infections and inflammatory diseases. Oxidative stress appears to be involved in the pathogenesis of these disorders, and associations have been found between homocysteine and e.g., neopterin concentration. Increased neopterin concentration indicates immune system activation and also allows an estimate of thus elicited oxidative stress. It may be relevant that the active cofactor, tetrahydrofolate, is very susceptible to oxidation. Immunologically induced oxidative stress could lead to folate depletion resulting in hyperhomocysteinemia. Thus, hyperhomocysteinemia in patients can be considered as an indirect consequence of hyperconsumption of antioxidant vitamins during prolonged states of immune activation.

[Clinical observation on effect of Xianlong capsule in treating vascular dementia].

OBJECTIVE: To study the effect of Xianlong Capsule (XLC) in treating vascular dementia (VD) and to explore its therapeutic mechanism. METHODS: The criteria of learning and memory related cholinergic nerve system, oxygen free radical and nitrogen monoxide (NO) in 35 patients with VD treated with XLC and 33 patients treated with hydergine were observed and compared with the normal control group. RESULTS: XLC could lower the acetylcholine esterase activity, increase the acetylcholine content in erythrocytes and plasma and decrease the NO content. No toxic adverse reaction was found in the observation period. CONCLUSION: XLC has definite effect in treating VD in aged patients, the therapeutic mechanism may be related with the actions in strengthening cholinergic nerve system, improving oxygen free radical metabolism, regulating NO and relieving its excitatory neurotoxicity.

[Clinical observation of effect on tongmai yizhi capsule in treating vascular dementia].

OBJECTIVE: To observe the effect of Tongmai Yizhi capsule (TMYZC) on learning in patients of vascular dementia (VD). METHODS: Thirty patients of VD were treated by oral administration of TMYZC, the changes in them before and after treatment were observed and compared with those in the 20 patients treated with hydergine as control. RESULTS: The total effective rate in the TMYZC treated group was 70.67% while that in the control group was 70.00%, the difference between the two groups was insignificant. CONCLUSION: Both TMYZC and hydergine have the effects of dilating blood vessels, increasing the cerebral blood flow, lowering the hyper-coagulative status and improving the free radical scavenging capability of patients.

[Effect of huancongdan capsule on lipoprotein, apolipoprotein and serum immunoglobulin in vascular dementia patients].

OBJECTIVE: To probe into the effect of Huancongdan capsule (HCDC) on the vascular dementia (VD) related factors, including lipoprotein, apolipoprotein (apo) and serum immunoglobulin. METHODS: Fifty-two patients of VD were divided into the HCDC group (27 patients, treated with HCDC) and the control group (25 patients, treated with Naofukang). Changes of related parameters were observed. RESULTS: The effects in lowering triglyceride and total cholesterol and elevating high density lipoprotein cholesterol in the HCDC group were superior to those in the control group (P < 0.01 or P < 0.05), but the effect in lowering low density lipoprotein cholesterol was similar in the two groups (P > 0.05). Compared with data before treatment, in the HCDC group after treatment, the levels of serum apoA1 increased, and serum apoB100, IgA, IgG and circulating immune complex decreased significantly (P < 0.05 or P < 0.01), but the change of apoE level was insignificant (P > 0.05). CONCLUSION: Through adjusting lipid metabolism, HCDC could improve blood rheologic characteristics, promote cerebral blood flow, improve the oxygen carrying capacity of blood to prevent and treat VD. One of its mechanisms is increasing apoA1 and decreasing apoB100 levels, preventing and improving atherosclerosis and reducing damage of vascular endothelial cells, the another may be its action in improving immune function.