Risk of Incident Atrial Fibrillation and Subsequent Use of Oral Anticoagulants in Patients with Dementia.

BACKGROUND: Dementia and atrial fibrillation (AF) have many shared risk factors. Besides, patients with dementia are under-represented in randomized trials, and even if AF is present, oral anticoagulants (OACs) are not prescribed frequently. This study aimed to report the incidence of newly diagnosed AF in dementia patients, and the impacts of use of vitamin K antagonist (VKA; e.g., warfarin) and non-VKA OAC (NOACs) on stroke and bleeding outcomes. METHODS: Our study utilized the Taiwan National Health Insurance Research Database. A total of 554,074 patients with dementia were compared with 554,074 age- and sex-matched patients without dementia regarding the risk of incident AF. Among patients with dementia who experienced incident AF, the risks of clinical events of patients treated with warfarin or NOACs were compared with those without OACs (reference group). RESULTS: The risk of incident AF was greater for patients with dementia compared with those without (adjusted hazard ratio [aHR]: 1.054; 95% confidence interval [CI]: 1.040-1.068 for all types of dementia, aHR: 1.035; 95% CI: 1.020-1.051 for presenile/senile dementia, and aHR: 1.125; 95% CI: 1.091-1.159 for vascular dementia). Among patients with dementia and experienced incident AF, warfarin use was associated with a higher risk of ischemic stroke (aHR: 1.290; 95% CI: 1.156-1.440), intracranial hemorrhage (ICH; aHR: 1.678; 95% CI: 1.346-2.090), and major bleeding (aHR: 1.192; 95% CI: 1.073-1.323) compared with non-OACs. NOAC use was associated with a lower risk of ischemic stroke (aHR: 0.421; 95% CI: 0.352-0.503) and composite risk of ischemic stroke or major bleeding (aHR: 0.544; 95% CI: 0.487-0.608) compared with non-OACs. These results were consistent among the patients after the propensity matching. CONCLUSION: In this large nationwide cohort, the risk of newly diagnosed AF was higher in patients with dementia (all dementia, presenile/senile dementia, and vascular dementia) compared with those without dementia. For patients with dementia who experienced incident AF, NOAC use was associated with a better clinical outcome compared with non-OAC. Patients with dementia require a holistic approach to their care and management, including the use of NOACs to reduce the risks of clinical events.

Acupuncture attenuates cognitive impairments in vascular dementia through inhibiting miR-143-3p.

BACKGROUND: Acupuncture can be used to treat vascular dementia (VD), but the underlying mechanism remains unclear. This study aimed to investigate the expression and clinical significance of microRNA-143-3p (miR-143-3p) in VD patients and explore whether acupuncture ameliorates VD by regulating miR-143-3p. METHODS: Cognitive function and daily living ability in VD patients were assessed by mini-mental state examination, Hasegawa's dementia scale and activities of daily living scale, respectively. VD model of male Wistar rats was established using permanent bilateral common carotid artery occlusion. The expression level of miR-143-3p was measured by quantitative real-time PCR. Morris water maze test was used to assess the cognitive function of VD rat model. Receiver operating characteristic analysis was used to assess the diagnostic value of miR-143-3p in VD patients. Correlations between variables were analyzed by Pearson's correlation analysis. RESULTS: Increased serum miR-143-3p expression in VD patients had a high diagnostic value to screen VD patients. Serum miR-143-3p level in VD patients after acupuncture treatment was decreased. After acupuncture treatment, serum miR-143-3p was negatively correlated with cognitive function and daily living ability in VD patients. miR-143-3p level was increased in VD rats, and the suppressive effects of acupuncture on miR-143-3p levels were relieved by miR-143-3p mimic. Overexpression of miR-143-3p reversed the ameliorative effect of acupuncture on cognitive functions of VD rats. CONCLUSION: Serum miR-143-3p expression is upregulated in VD patients and downregulated in VD patients after acupuncture treatment. Additionally, acupuncture treatment may attenuate cognitive impairments in VD by suppressing miR-143-3p.

Efficacy and safety of Buyang Huanwu-Tang (Boyang Hwano-Tang) in patients with vascular dementia: A protocol of systematic review and meta analysis.

BACKGROUND: Vascular dementia (VaD) is the second most common type of dementia; it has a significant impact on patients and exerts a great social and economic burden. However, there has been no comprehensive systematic review assessing the efficacy and safety of Buyang Huanwu-Tang (Boyang Hwano-Tang, BHT) for VaD. Therefore, this protocol was developed to conduct a comprehensive systematic review and meta-analysis to evaluate the effectiveness and safety of BHT in the treatment of VaD. METHODS: We will perform a comprehensive electronic search including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, PsycARTICLES, Oriental Medicine Advanced Searching Integrated System, Korean Studies Information Service System, Research Information Service System, Korean Medical Database, KMbase, National Digital Science Library, China National Knowledge Infrastructure, Wanfang database, VIP database, Citation Information by NII, and other sources from their inception to November 25, 2020. This systematic review will include only randomized controlled clinical trials of BHT for VaD. The main outcomes will include the Mini-Mental State Examination, Montreal Cognitive Assessment, and Revised Hasegawa's Dementia Scale. Two researchers will independently conduct study selection, data extraction, and appraise the quality and risk of bias of the included studies. A meta-analysis will be conducted using Review Manager version 5.4. The evidence quality of each outcome will be appraised according to the Grades of Recommendation, Assessment, Development, and Evaluation. RESULTS: This study will provide comprehensive understanding of the efficacy and safety of BHT for the treatment of VaD. CONCLUSIONS: The findings of this study will provide reliable evidence for clinical application and further study of BHT for VaD. ETHICS AND DISSEMINATION: Ethical approval is not required because individual patient data will not be included in this study. The study findings will be disseminated through conference presentations. OSF REGISTRATION DOI: 10.17605/OSF.IO/NDYGP.

Profunda femoris pseudoaneurysm rupture post dynamic hip screw fixation after physiotherapy.

This case discusses an elderly female who presented acutely with compromised profunda femoris pseudoaneurysm and massive haematoma five weeks after dynamic hip screw insertion for a left neck of femur fracture. The only precipitating factor leading to this presentation was ongoing physiotherapy. She was referred from a rehabilitation hospital to the nearest vascular surgical unit for acute and definitive surgical intervention. Post-operatively, she fared incredibly well, regaining her baseline level of functioning. History taking is complex in a patient with dementia. Clinical examination should follow with a focused approach to the site of recent operation and also where complications are likely to manifest when an alteration from baseline cognitive function is noted. This is of course in addition to the complete work up required from a holistic perspective with any acute deterioration. Imaging should be arranged and prompt referral made if a treatable acute cause is identified. It is imperative to involve family and/or next of kin if possible, but this should not impede prompt decision-making in the patient's best interests by the clinical team if delays are likely to occur.

Marinoid J, a phenylglycoside from Avicennia marina fruit, ameliorates cognitive impairment in rat vascular dementia: a quantitative iTRAQ proteomic study.

CONTEXT: Fruit of Avicennia marina (Forsk.) Vierh. (Acanthaceae) is used as a Chinese herb. Studies have found that it contains marinoid J, a novel phenylethanoid glycoside (PG) compound, but its neuroprotective functions are largely unknown. OBJECTIVE: This study evaluated the effects of marinoid J on vascular dementia (VD) and determined its potential mechanisms of action. MATERIALS AND METHODS: The VD model was established by the ligation of the bilateral common carotid artery in Sprague-Dawley rats, who received daily intragastrically administration of saline, marinoid J (125 or 500 mg/kg body weight/d), or oxiracetam (250 mg/kg body weight/d) for 14 days (20 rats in each group). The Morris water maze (MWM) was used to evaluate cognitive performance. The hippocampus was subjected to histological and proteomic analyses. RESULTS: Marinoid J shortened the escape latency of VD rats (31.07 ± 3.74 s, p < 0.05). It also decreased malondialdehyde (MDA) (27.53%) and nitric oxide (NO) (20.41%) while increasing superoxide dismutase (SOD) (11.26%) and glutathione peroxidase (GSH-Px) (20.38%) content in hippocampus tissues. Proteomic analysis revealed 45 differentially expressed proteins (DEPs) in marinoid J-treated VD rats, which included angiotensin-converting enzyme (ACE), keratin 18 (KRT18), cluster of differentiation 34 (CD34), and synaptotagmin II (SYT2). CONCLUSIONS: Marinoid J played a role in protecting hippocampal neurons by regulating a set of proteins that influence oxidative stress and apoptosis, this effect may thereby alleviate the symptoms of VD rats. Thus, pharmacological manipulation of marinoid J may offer a novel opportunity for VD treatment.

Association of nimodipine and choline alphoscerate in the treatment of cognitive impairment in patients with cerebral small vessel disease: study protocol for a randomized placebo-controlled trial-the CONIVaD trial.

BACKGROUND: Vascular cognitive impairment (VCI) is an extremely disabling condition that includes post-stroke dementia and VCI caused by cerebral small vessel disease (SVD). Currently, there is no approved treatment for this condition. Drugs active on the cholinergic pathway have been tested in VCI patients showing positive but limited efficacy. The calcium-antagonist nimodipine also showed some moderate positive effects in VCI patients. AIMS: CONIVaD (choline alphoscerate and nimodipine in vascular dementia) is a pilot, single-center, double-blinded, randomized trial aimed to assess whether the association of choline alphoscerate and nimodipine is more effective than nimodipine alone in reducing cognitive decline in patients with SVD and mild-to-moderate cognitive impairment. METHODS: All patients are evaluated at baseline and after 12 months with: (1) clinical, daily functions, quality of life, and mood assessment and (2) extensive neuropsychological evaluation. After the baseline evaluation, patients are randomly assigned to one of the two arms of treatment: (1) nimodipine 90 mg/die t.i.d plus placebo b.i.d and (2) nimodipine 90 mg t.i.d plus choline alphoscerate 1200 mg/die b.i.d. for a total of 12 months. The primary endpoint is cognitive decline, expressed as the loss of at least two points on the Montreal Cognitive Assessment at 12 months. Secondary endpoints include safety and tolerability, functional, quality of life, and neuropsychological measures. DISCUSSION: CONIVaD study is the first randomized controlled trial to examine the cognitive efficacy of combined choline alphoscerate-nimodipine treatment in VCI patients. Results of this pilot study will serve as a methodological basis for other clinical controlled, multicentric, double-blinded, and randomized trials. TRIAL REGISTRATION: Clinical Trial NCT03228498. Registered 25 July 2017.

[Treatment of refractory aggressiveness by amygdalotomy and posteromedial hypothalamotomy by radiofrequency]. / Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.

INTRODUCTION: Since, under certain circumstances, defensive or attacking behaviours display a pattern of motor dominance, as observed in subjects who participate in contact or fighting sports, aggressive behaviour was considered to have a dominant motor pattern. With the aim of preventing the functional problems reported with bilateral lesion procedures involving both the central nucleus of the amygdala and the posteromedial hypothalamus, the decision was made to combine them; thus, an amygdalotomy of the central nucleus of the amygdala and a posteromedial hypothalamotomy were to be performed simultaneously and unilaterally, on the basis of the motor dominance of the patient determined by means of the Edinburgh test. PATIENTS AND METHODS: This study describes the surgical experience in a series of nine patients diagnosed with refractory neuroaggressive syndrome. As part of the study protocol, a magnetic resonance brain scan was performed to rule out the presence of neoplasms, vascular diseases, infections and degenerative disorders. The degree of aggressiveness was quantified using Yudofsky's Overt Aggression Scale. Additionally, manual dominance was determined by means of the Edinburgh test. RESULTS AND CONCLUSIONS: Good control of aggressiveness was seen immediately. In some cases it was necessary to reduce the antipsychotic or benzodiazepine medication, as it was seen to increase aggressiveness. Only one case required a second surgical intervention. Follow-up was achieved in 100% of the cases at 24 months and 78% at 36 months.

TITLE: Tratamiento de la agresividad refractaria mediante amigdalotomia e hipotalamotomia posteromedial por radiofrecuencia.Introduccion. Dado que, en algunas circunstancias, las conductas defensivas o de ataque muestran un patron de dominancia motora, tal como se observa en los sujetos dedicados a los deportes de contacto o de lucha, se considero que la conducta agresiva tiene un patron motor dominante. Con el fin de evitar los problemas funcionales descritos con los procedimientos de lesion bilateral tanto del nucleo central de la amigdala como del hipotalamo posteromedial, se decidio combinarlos; es decir, realizar amigdalotomia del nucleo central de la amigdala e hipotalamotomia posteromedial de manera unilateral y simultanea, basandose en la dominancia motora del paciente mediante la prueba de Edimburgo. Pacientes y metodos. Este estudio muestra la experiencia quirurgica en una serie de nueve pacientes con el diagnostico de sindrome neuroagresivo resistente al tratamiento farmacologico. Dentro del protocolo de estudio, se les realizo resonancia magnetica cerebral para descartar la presencia de neoplasias, enfermedades vasculares, infecciones y trastornos degenerativos. El grado de agresividad se cuantifico mediante la escala global de agresividad de Yudofsky. Adicionalmente, se determino la dominancia manual a traves de la prueba de Edimburgo. Resultados y conclusiones. El buen control de la agresividad se observo de modo inmediato. En algunos casos fue necesario reducir la medicacion de antipsicoticos o benzodiacepinas, ya que aumentaban la agresividad. Solo un caso requirio una segunda cirugia. Se logro seguimiento del 100% de los casos en 24 meses y del 78% en 36 meses.

Effect of medicated thread moxibustion on apoptosis of hippocampal neurons in rat models of chronic cerebral ischemic vascular dementia.

To investigate the effect of medicated thread moxibustion onapoptosis in hippocampal neuronsin a rat model of chronic cerebral ischemic vascular dementia. A total of 40 male Wistar rats were randomly divided into normal group and sham-operated group (7 rats each), and rat model of chronic cerebral ischemic vascular dementia (14 rats). The model group rats were treated with medicated thread moxibustion two weeks after surgery, once a day, with one day break every six days, (24 times in all)and an observation period of 4 weeks. At the end of therapy, H&E staining was used to monitor changes in the neurons in CA1 area of the rat hippocampus. Changes in related indexes such as Bax, Bc1-2 and C-fos of neuron apoptosis in hippocampus CA1 area were determined by immunohistochemistry, while protein expression was semi-quantitatively assayed using imaging analysis technique. There was significant hippocampal neuronal necrosis six weeks after model establishment, but the necrosis was milder in rats in the medicated thread moxibustion group. Bax and C-fos were positively expressed and significantly higher in the hippocampus of chronic cerebral ischemic vascular dementia rats (model group) than in the medicated thread moxibustion group after treatment (p <0.01). The expression of Bcl-2 was increased in the medicated thread group after treatment, and was higher in the model group, but comparable to that in the sham-operated group (p=0.975>0.05). Medicated thread moxibustion alleviates hippocampal neuronal necrosis, inhibits neuron apoptosis in hippocampus CA1 area, protects nerves, and maintains relative equilibrium inBax/Bcl-2 through down-regulation of C-fos and Bax and up-regulation of Bcl-2. Thus, cell apoptosis-related pathway may be one of its mechanisms of action.

Acupuncture as a multifunctional neuroprotective therapy ameliorates cognitive impairment in a rat model of vascular dementia: A quantitative iTRAQ proteomics study.

AIMS: Acupuncture has been reported to affect vascular dementia through a variety of molecular mechanisms. An isobaric tag for relative and absolute quantification (iTRAQ) with high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses makes it possible to attain a global profile of proteins. Hence, we used an iTRAQ-LC-MS/MS strategy to unravel the underlying mechanism of acupuncture. METHODS: Wistar rats were subjected to vascular dementia with bilateral common carotid occlusion. Acupuncture was intervened for 2 weeks at 3 days after surgery. The Morris water maze was used to assess the cognitive function. Proteins were screened by quantitative proteomics and analyzed by bioinformatic analysis. Four differentially expressed proteins (DEPs) were validated by western blot. The reactive oxygen species (ROS) production, neuron cell loss, and long-term potentiation (LTP) were determined after western blot. RESULTS: Acupuncture at proper acupoints significantly improved cognitive function. A total of 31 proteins were considered DEPs. Gene ontology (GO) analysis showed that most of the DEPs were related to oxidative stress, apoptosis, and synaptic function, which were regarded as the major cellular processes related to acupuncture effect. Western blot results confirm the credibility of iTRAQ results. Acupuncture could decrease ROS production, increase neural cell survival, and improve LTP, which verified the three major cellular processes. CONCLUSION: Acupuncture may serve as a promising clinical candidate for the treatment of vascular dementia via regulating oxidative stress, apoptosis, or synaptic functions.

A Study of a Supplement Containing Huperzine A and Curcumin in Dementia Patients and Individuals with Mild Cognitive Impairment.

Extracts from Huperzia serrata (HS) function as a cholinesterase inhibitor and a glutamic acid receptor antagonist. We tested a supplement containing HS extracts, curcumin, and others in dementia patients and individuals with mild cognitive impairment (MCI) in an open label study. Most patients with Alzheimer's disease, dementia with Lewy bodies, and MCI individuals exhibited improvements in cognitive functions, as assessed by the Alzheimer's Disease Assessment Scale-cognitive subscale Japanese version. The scores were significantly improved at 6-12 weeks compared with baseline scores (p = 0.007) and at 22-28 weeks (p = 0.004). Thus, this supplement may be administered to dementia patients as well as MCI individuals.

Acupuncture inhibits TXNIP-associated oxidative stress and inflammation to attenuate cognitive impairment in vascular dementia rats.

AIMS: Oxidative stress and inflammation have been implicated in the pathogenesis of vascular dementia (VD). Thioredoxin-interacting protein (TXNIP) plays a vital role in oxidative stress and NOD-like receptor protein 3 (NLRP3) inflammasome activation. There is evidence that acupuncture has an antioxidative and neuroprotective effect in VD. In this study, we investigated whether acupuncture can attenuate cognitive impairment via inhibiting TXNIP-associated oxidative stress and inflammation in VD rats. METHODS: Both common carotid arteries were occluded (2-vessel occlusion [2VO]) in rats to model VD. The neuroprotective effect of acupuncture was assessed by the Morris water maze and Nissl staining. Oxidative stress was assessed by detecting levels of reactive oxygen species, DNA oxidation, and antioxidase. Western blot, real-time PCR, and immunofluorescence were used to detect the expression of TXNIP, NLRP3, caspase-1, and IL-1ß. A TXNIP siRNA intraventricular injection was applied to investigate whether acupuncture mimicked the effect of TXNIP inhibitor. RESULTS: Our findings demonstrated that VD rats treated with acupuncture had reduced hippocampal neuronal loss and oxidative stress. The upregulation of TXNIP, NLRP3, caspase-1, and IL-1ß induced by 2VO was also reversed by acupuncture. Furthermore, TXNIP siRNA had a similar effect as acupuncture on cognition, hippocampal neurons, and ROS production in VD rats. CONCLUSION: In conclusion, our study suggests that the neuroprotective effects of acupuncture in VD are mediated through reducing expression of TXNIP-associated oxidative stress and inflammation.

Acupuncture Attenuated Vascular Dementia-Induced Hippocampal Long-Term Potentiation Impairments via Activation of D1/D5 Receptors.

BACKGROUND AND PURPOSE: Emerging evidence suggests that acupuncture could improve cognitive impairment in vascular dementia by enhancing synaptic plasticity in the hippocampus. The purpose of this study is to investigate whether dopamine, a key mediator of synaptic plasticity, is involved in this cognitive improvement. METHODS: Vascular dementia model was established by bilateral common carotid arteries occlusion in male Wistar rats. Three days after the operation, animals received acupuncture treatment for 2 weeks, once daily. The D1/D5 receptors antagonist SCH23390 was administered intraperitoneally 15 minutes before each acupuncture treatment. Morris water maze was examined after acupuncture. Long-term potentiation was studied by an electrophysiological technique. Dopamine and metabolites levels were detected by microdialysis and high-performance liquid chromatography from brain tissue. The expression of D1R and D5R was analyzed by immunofluorescence. RESULTS: Acupuncture remarkably reversed cognitive deficits in 2-vessel occlusion model (2VO) rats, and the acupuncture points Zusanli (ST36) and Baihui (GV20) were confirmed to be the most effective combination. Electrophysiological recording data showed that 2VO-induced impairments of long-term potentiation were prevented by acupuncture. In addition, acupuncture promoted the release of dopamine and its major metabolites in the hippocampus of 2VO rats. The immunofluorescence experiment showed that the decrease of D1R and D5R in hippocampal dentate gyrus region of 2VO rats was reversed by acupuncture. Furthermore, we found that the effects of acupuncture against 2VO-induced impairments in cognition and synaptic plasticity were abolished by SCH23390. CONCLUSIONS: Improvement in cognition and hippocampal synaptic plasticity induced by acupuncture was achieved via activation of D1/D5 receptors in 2VO rats.

Common 1H-MRS Characteristics in Patients With Alzheimer's Disease and Vascular Dementia Diagnosed With Kidney Essence Deficiency Syndrome: A Preliminary Study.

Context • Traditional Chinese medicine (TCM) indicates that both Alzheimer's disease (AD) and vascular dementia (VD) should be categorized as dementia and that they have a common etiology and pathogenesis under TCM classification of syndromes, such as with kidney essence deficiency syndrome (KEDS). The pathological location is mainly in the brain. However, it remains unclear whether AD and VD patients with KEDS exhibit a metabolic commonality in the same region of the brain. Objective • The study intended to investigate the metabolic characteristics of the brain using proton magnetic resonance spectroscopy (1H-MRS) in patients with AD and VD who had been diagnosed with KEDS. Design • The research team designed a pilot study, with the participants being allocated to 3 groups: (1) an AD group, (2) a VD group, and (3) a control group. All data analysis was carried out by a trained radiologist who was blinded to each participant's diagnosis. Setting • The study took place at the Tongde Hospital of Zhejiang Province (Zhejiang Sheng, China). Participants • Participants were patients at the Tongde Hospital with mild AD or VD who had been diagnosed with KEDS. The normal controls were patients' spouses or guardians with normal cognitive function. Outcome Measures • All participants underwent 1H-MRS. The N-acetyl aspartate (NAA)/myo-inositol (mI), NAA/creatine (Cr), choline (Cho)/Cr, and mI/Cr ratios were bilaterally measured in the posterior cingulate gyrus (PCG) and anterior cingulate gyrus (ACG) by the Syngo spectroscopy postprocessing package. Demographic characteristics and 1H-MRS data were assessed across the AD, VD, and normal control groups. Results • Thirteen patients with mild AD with KEDS, 15 patients with mild VD with KEDS, and 18 normal controls were recruited from May 2013 through May 2014. The AD and VD groups did not significantly differ in the NAA/mI, NAA/Cr, Cho/Cr, and mI/Cr ratios in either the PCG or the ACG, with the exception being the Cho/Cr ratio in the right ACG, for which the ratio of the AD group was significantly lower when compared with that of the VD group (P < .05). Conclusions • Mild AD and VD with KEDS showed similar patterns for the 1H-MRS on the cingulate cortex, providing evidence for a common pathogenesis for the KEDS that is associated with AD and VD, providing a modern biological basis for the philosophy of providing the same treatment for different diseases.

Bright light therapy for sleep disturbance in dementia is most effective for mild to moderate Alzheimer's type dementia: a case series.

BACKGROUND: Sleep problems in people with dementia are common and place a high burden on caregivers. Although hypnotic agents are often used to treat sleep disturbances, their use is associated with a considerable number of high-risk side-effects such as daytime sleepiness, amnesia, and an increased frequency of falling. The administration of bright light therapy (BLT) in the morning was a non-pharmacological remedy that was expected to treat sleep disorders in patients with dementia by entraining the circadian rhythm to ameliorate disturbances to the normal sleep-wake cycle. However, there are some unsolved issues related to the application of BLT, including the types of dementia for which it is effective and its efficacy in the different stages of cognitive decline and dementia. Furthermore, a protocol for effective BLT has not yet been proposed. METHODS: In this study, we explored the efficacy of BLT in the treatment of 17 participants, including those with Alzheimer's type dementia (AD) (n = 8), vascular dementia (n = 4), and dementia with Lewy bodies (n = 5). Patients sat in front of the light box for 1 h/day from 0900 to 1000. The patients underwent treatment every day for 2 weeks. RESULTS: BLT led to the improvement of sleep disturbance in four participants, all of whom were AD patients. The four AD patients showed a shorter duration of illness and/or had mild to moderate AD. CONCLUSION: BLT could be an effective strategy for treating dementia patients, depending on their type and grade of their dementia. To confirm this hypothesis, it would be necessary to study a larger number of cases. Non-pharmacological therapies for sleep disorders should be emphasized as a safe form of treatment for patients with dementia.

Effects of equol on deoxycorticosterone acetate salt-induced hypertension and associated vascular dementia in rats.

Oxidative stress is the major cause of neuronal cell degeneration observed in neurodegenerative diseases including vascular dementia (VaD), and hypertension has been found to increase the probability of VaD. Here, we investigated the effects of equol in deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats (DHRs) and the associated VaD. The systolic blood pressure of rats treated with low- (10 mg per kg body weight) and high-dose (20 mg per kg body weight) equol for 4 weeks was lower than that of the control group by 12.18 and 17.48% in a dose-dependent manner, respectively (p < 0.05), which was regulated by inhibiting angiotensin-converting enzyme (ACE) activity and increasing the nitric oxide (NO) production. Equol-treated DHRs showed a significant decrease in both the swimming distance and time required to reach the escape platform (78.20 to 82.56%, p < 0.05). In addition, the probe trial session and working memory test indicated that equol improved the long- and short-term memory of the rats. Moreover, the brain antioxidant activity was increased by elevating the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels, and the malondialdehyde (MDA) content and acetylcholinesterase (AChE) activity were decreased, indicating that equol suppressed oxidative stress. In conclusion, we demonstrated that equol exhibited comparable blood pressure (BP)-lowering and VaD-improving effects with the clinically used drug, lisinopril in DHRs while there was a positive correlation between the doses. Therefore, this bioactive compound may be useful for developing functional foods, thereby extending the application of equol-containing crops.

Glycyrrhizic Acid Ameliorates Cognitive Impairment in a Rat Model of Vascular Dementia Associated with Oxidative Damage and Inhibition of Voltage-Gated Sodium Channels.

Vascular dementia (VD) is the second most common cause of cognitive impairment in the elderly population. Our study aims to investigate the neuroprotective effects of glycyrrhizic acid (GA), a major active constituent of Glycyrrhiza glabra root, in a VD rat model induced by permanent occlusion of the bilateral common carotid arteries. Spatial cognitive function was examined by the Morris water maze test and synaptic plasticity was explored by assessing long-term potentiation. The results showed that GA (20 mg/kg for 5 days) significantly improved the performance of learning and memory of VD rats in the Morris water maze test and attenuated induction of long-term potentiation. Histopathological studies showed that GA significantly attenuated cell damage in VD rats. Malondialdehyde levels and superoxide dismutase activity were analyzed in the hippocampus and cortex to investigate anti-oxidant status. The results showed that GA decreased the level of lipid peroxidation and increased the activity of superoxide dismutase in VD rats. Lastly, whole-cell patch-clamp analysis was used to examine the effect of GA on voltage-gated sodium channels (VGSCs) in hippocampal CA1 pyramidal neurons. GA (10, 20 and 50 µM) inhibited the current amplitude of the VGSCs. These results suggest that the neuroprotective e.ects of GA in VD rats relate to the reduction of oxidative stress and inhibition of VGSCs. Our study provides experimental evidence for the application of GA in the treatment of cognitive deficits induced by Alzheimer's disease, stroke, or traumatic brain injury.

Accelerated Vascular Aging as a Paradigm for Hypertensive Vascular Disease: Prevention and Therapy.

Aging is considered the most important nonmodifiable risk factor for cardiovascular disease and death after age 28 years. Because of demographic changes the world population is expected to increase to 9 billion by the year 2050 and up to 12 billion by 2100, with several-fold increases among those 65 years of age and older. Healthy aging and prevention of aging-related diseases and associated health costs have become part of political agendas of governments around the world. Atherosclerotic vascular burden increases with age; accordingly, patients with progeria (premature aging) syndromes die from myocardial infarctions or stroke as teenagers or young adults. The incidence and prevalence of arterial hypertension also increases with age. Arterial hypertension-like diabetes and chronic renal failure-shares numerous pathologies and underlying mechanisms with the vascular aging process. In this article, we review how arterial hypertension resembles premature vascular aging, including the mechanisms by which arterial hypertension (as well as other risk factors such as diabetes mellitus, dyslipidemia, or chronic renal failure) accelerates the vascular aging process. We will also address the importance of cardiovascular risk factor control-including antihypertensive therapy-as a powerful intervention to interfere with premature vascular aging to reduce the age-associated prevalence of diseases such as myocardial infarction, heart failure, hypertensive nephropathy, and vascular dementia due to cerebrovascular disease. Finally, we will discuss the implementation of endothelial therapy, which aims at active patient participation to improve primary and secondary prevention of cardiovascular disease.

Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca(2+)-CaMKII-CREB pathway.

The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.

Acupuncture attenuates cognitive deficits and increases pyramidal neuron number in hippocampal CA1 area of vascular dementia rats.

BACKGROUND: Decreased cognition is recognized as one of the most severe and consistent behavioral impairments in dementia. Experimental studies have reported that acupuncture may improve cognitive deficits, relieve vascular dementia (VD) symptoms, and increase cerebral perfusion and electrical activity. METHODS: Multi-infarction dementia was modeled in rats with 3% microemboli saline suspension. Two weeks after acupuncture at Zusanli (ST36), all rats were subjected to a hidden platform trial to test their 3-day spatial memory using the Morris water maze test. To estimate the numbers of pyramidal neuron, astrocytes, and synaptic boutons in hippocampal CA1 area, we adopted an unbiased stereology method to accurately sample and measure the size of cells. RESULTS: We found that acupuncture at ST36 significantly decreased the escape latency of VD rats. In addition, acupuncture significantly increased the pyramidal neuron number in hippocampal CA1 area (P < 0.05) and tended to decrease the number of astrocytes (P = 0.063). However, there was no significant change in the synaptic bouton number of hippocampal CA1 area in any of the groups (P > 0.05). CONCLUSIONS: These findings suggest that acupuncture may improve cognitive deficits and increase pyramidal neuron number of hippocampal CA1 area in VD rats.