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OBJECTIVE Alzheimer's disease(AD)and vascular dementia(VD)are the primary causes of dementia in elderly individuals,and therapeutic options for both conditions are limited.Overactivation of N-methyl-D-aspartate(NMDA)receptors,decreased cerebral blood flow,and subsequent pathological events,play signifi-cant roles in the progression of AD and VD.METHODS In this study,we investigated the therapeutic effects and underlying mechanisms of MN-08,a novel memantine nitrate,in mouse models of AD and rats with VD.RESULTS MN-08 was found to inhibit Aβ accumulation,prevent neuronal and dendritic spine loss,and attenuate cognitive deficits in 2-month-old APP/PS1 transgenic mice(following a 6-month preventative course)and in 8-month-old triple-transgenic(3×Tg-AD)mice(following a 4-month therapeutic course),as well as in rat models of VD with preventive and therapeutic treatments.In vitro,MN-08 was shown to bind to and antagonize NMDA receptors,inhibit calcium influx,and reverse dysregula-tions of the ERK and PI3K/Akt/GSK3β pathway,subse-quently preventing glutamate-induced neuronal loss.Additionally,MN-08 exhibited favorable pharmacokinet-ics,blood-brain barrier penetration,and safety profiles in rats and beagle dogs.CONCLUSION These findings suggest that the novel memantine nitrate MN-08 may be a useful therapeutic agent for AD and VD.
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Objective:To investigate whether memantine hydrochloride (MEM) could promote the bactericidal effect of neutrophils against methicillin-resistant Staphylococcus aureus (MRSA) and the possible mechanism. Methods:Neutrophils were co-incubated with different concentrations of MEM and MRSA for 4 h. Then the cell lysates were collected and cultured on plate for survival bacteria counting. After co-incubation, the neutrophils were collected to detect the production of reactive oxygen species (ROS) and the release of neutrophil extracellular traps (NETs). A mouse model of MRSA infection was established, and then the mice were treated with or without MEM. Blood, spleen and kidney samples were collected from the mice for bacterial colony counting and blood procalcitonin (PCT) detection. In the 48 h survival experiment, the mice were first infected with MRSA, and then treated with MEM or PBS. The survival rates of the mice were calculated and the survival curves were drawn.Results:The number of MRSA co-cultured with neutrophils decreased significantly in the presence of MEM, and within a certain concentration range, the survival number of MRSA decreased with the increase of MEM concentration. Moreover, MEM could significantly promote the production of ROS by neutrophils and the formation of NETs. In vivo experiment showed that the concentration of PCT in mouse blood samples was lower in the MRSA+ MEM group than in the MRSA+ PBS group. The animal experiment also revealed that MEM significantly decreased the bacteria loads in mouse blood and organs and increased the 48 h survival rate after MRSA infection.Conclusions:MEM could significantly promote the bactericidal effect of neutrophils against MRSA, which might be related to the enhanced generation of ROS by neutrophils and the formation of NETs.
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ABSTRACT. Brain metastases are the most common central nervous system tumors. The mainstay treatment for this tumor in low to middle income countries is whole brain radiation therapy. Irreversible cognitive decline is associated with the use of whole brain radiotherapy. Several pharmacologic and nonpharmacologic options have been employed in studies focusing on the prevention of cognitive decline following whole-brain radiation therapy. Memantine use has been shown to provide some benefit in reducing the rate of decline in cognitive function and time to cognitive failure. The objective of this review article is to provide a summary on available primary literature on the therapeutic role of memantine for the prevention of cognitive decline in cancer patients with brain metastasis receiving whole brain radiotherapy.
RESUMO. As metástases cerebrais são os tumores mais comuns do sistema nervoso central. O tratamento principal para este tumor em países de baixa e média renda é a radioterapia de cérebro inteiro. O declínio cognitivo irreversível está associado ao uso de radioterapia cerebral total. Várias opções farmacológicas e não farmacológicas têm sido empregadas em estudos com foco na prevenção do declínio cognitivo após radioterapia de cérebro inteiro. O uso de memantina demonstrou fornecer algum benefício na redução da taxa de declínio na função cognitiva e no tempo até a falha cognitiva. O objetivo deste artigo de revisão foi fornecer um resumo da literatura primária disponível sobre o papel terapêutico da memantina para a prevenção do declínio cognitivo em pacientes com câncer com metástase cerebral recebendo radioterapia cerebral total.
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HumanosRESUMO
@#Introduction: Minocycline has been demonstrated to have potent effects on neurologic structures and functions in several animal models. However, its neuroprotective properties following a single injection of lipopolysaccharide (LPS) in an adult rat model have not been clearly elucidated. This study investigated minocycline’s neuroprotective effects in the LPS-induced neuroinflammation rat model. Methods: Fifty adult male Sprague Dawley rats were split into five groups at random: (i) control, (ii) distilled water-treated LPS, (iii) 25 mg/kg minocycline-treated LPS, (iv) 50 mg/kg minocycline-treated LPS, and (v) 10 mg/kg memantine-treated LPS. On day 5, LPS (5 mg/kg) was given intraperitoneally once, whereas minocycline and memantine were given once daily for 14 days. Results: LPS was found to significantly induce β-amyloid peptide deposition and neuronal damage, and impair recognition memory, while administration of minocycline dose-dependently reversed these effects. These data suggest that LPS-induced recognition memory impairment by inducing β-amyloid peptide deposition and neuronal damage in the cortical and hippocampal areas. Furthermore, we compared minocycline with memantine administration, and these data suggested better effects in minocycline (50 mg/kg) and comparable effects between minocycline (25 mg/kg) and memantine (10 mg/kg) treatments in reducing β-amyloid peptide deposition, neuronal damage and recognition memory impairment induced by LPS. Conclusion: Minocycline may be a strong contender as an effective preventive-therapeutic drug for neuroinflammatory diseases such as Alzheimer’s disease (AD) based on these findings.
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Objective:To assess the safety and efficacy of Anthocyanins for the treatment of Alzheimer's disease.Methods:From November 2018 to December 2020, a multicenter, double-blind, randomized controlled clinical study was conducted in 6 hospitals.The regular medication for the two groups was memantine, with the addition of a combination preparation containing Anthocyanins for the experimental group and a placebo for the control group.The Mini-Mental State Scale(MMSE), Montreal Cognitive Assessment Scale(MoCA), Alzheimer's Disease Assessment Scale-Cognitive Subscale(ADAS-cog), Activities of Daily Living Scale(ADCS-ADL)and Hamilton Depression Scale(HAMD)were used for assessment at the beginning.After 16 weeks of treatment, MMSE, MoCA, ADCS-ADL, ADAS-cog and the Clinician's Interview-Based Impression of Change Plus Caregiver Input(CIBIC-Plus)Scale were conducted and adverse events were recorded.Results:A total of 66 patients were enrolled, with 33 in the control group and 33 in the experimental group.There were no significant differences in cognitive function scores between the two groups before enrollment.Differences in MMSE scores, MOCA scores and ADAS-cog scores before and after treatment between the control group and the experimental group were 1.9±2.4 vs.3.4±2.0( t=2.62, P=0.011), 1.8±1.9 vs.2.9±1.4( t=2.45, P=0.018)and 3.0±2.3 vs.5.3±4.6( t=2.45, P=0.019), respectively.The differences were statistically significant.Instrumental activities of daily living(IADL)scores before and after treatment in the control group were 21.6±5.7 vs.22.6±6.2( t= 2.09, P= 0.046), and those in the experimental group were 22.7±5.4 vs.23.4±5.4( t= 2.45, P= 0.021). The differences between the two groups before and after treatment were statistically significant. Conclusions:Treatment with Anthocyanins can delay the decline of cognitive function and activities of daily living ability in patients with Alzheimer's disease.Anthocyanins may be a promising therapeutic drug for Alzheimer's disease in the future.
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OBJECTIVE：To investiga te the clinical efficacy and safety of donepezil monotherapy versus donepezil combined with memoriam in the treatment of Alzheimer ’s disease （AD）. METHODS ：Totally 100 patients with moderate and severe AD who received medical care in Sichuan Academy of Medical Sciences & Sichuan Provincial People ’s Hospital （East Hospital ）from March 2018 to March 2020 were enrolled as study subjects ，and then were divided into control group and treatment group randomly. Control group was given donepezil monotherapy treatment （initial dose of 5 mg/d，before bedtime ；after 4 weeks，the dose was changed to 10 mg/d before bedtime ；the total medication time was 6 months）. Treatment group was treated with memantine（initial dose was 5 mg/d，the dose of those without adverse reactions was increased by 5 mg until 20 mg/d，for 6 months）on the basis of the control group ，with 50 patients in each group. Montreal cognitive assessment scale （MoCA）score， MMSE score ，ADL score ，treatment response rate and the occurrence of ADR were compared between 2 groups before and after treatment. RESULTS ：Compared with same group before treatment ，MoCA score ，MMSE score and ADL score of the two groups were significantly improved after treatment （P＜0.05）. After treatment ，compared with control group ，MoCA score ，MMSE score ， ADL score and total response rate in the treatment group were significantly increased （P＜0.05），while the incidence of ADR was decreased significantly （P＜0.05）. CONCLUSIONS ：Donepezil combined with memantine has better clinical efficacy than donepezil monotherapy in the treatment of moderate and severe AD ，and is helpful to improve the neurological function of AD patients，with good safety.
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@#Memantine is NMDA (N Methyl D Aspartate) antagonist used to manage dementia, it works by blocking the glutamate receptors that stimulate excite-toxic neuronal death that results from excessive calcium influx into the neurons which in turn causes mitochondrial suffocation and neuronal death. Memantine is an uncompetitive, low affinity, open-channel blocker that reduces the glutamate induced overstimulation of the receptors that results in neuronal damage. It is unlike potential neuroprotective agents that block virtually all NMDA receptor activity including blockade of those essential for normal neuronal functioning. On the other hand, the pathology of dementia we are tackling here appears several years and may be decades earlier in structural and functional MRI studies before the development of the full-blown clinical picture of Alzheimer’s Dementia. The use of Meantime in this paper is targeting the excite-toxic etiology mainly and the development of Alzheimer’s Dementia. We used the term and definitions of critical numbers in a synonymous way to talk about brain reserve and to hypothesize the potential mechanism of Memantine in delaying the onset of symptoms of Alzheimer’s Dementia if used as a monotherapy irrespective of other pathologies such as the neurofibrillary tangles and plaques formation. Meanwhile, in the same hypothesis we left a room for using memantine and other disease modifying agents to be combined and used to tackle more than one etiological factor in those individuals with genetic risk to develop Alzheimer’s Dementia with and without cardiovascular risk factors.
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Background: The study was done with the objective to evaluate synergistic activity of ketamine induced general anesthesia by memantine in wistar albino rats.Methods: The wistar albino rats of either sex were divided into four groups of five animals. Group 1 received ketamine 40 mg/kg, group 2 received ketamine 80 mg/kg, group 3 received ketamine 40 mg/kg along with memantine 10 mg/kg and group 4 received 80 mg of ketamine along with memantine 10 mg/kg to evaluate the synergistic activity of ketamine induced general anesthesia by memantine. The sleep latency time and duration of sleep were measured in all the groups.Results: The sleep latency time of group 4 is significantly decreased (p<0.001) compared to all other groups. The duration of sleep of group 4 is significantly increased (p<0.001) compared to group 1 and group 3, but less than that of group 1.Conclusions: Memantine possess synergistic activity of ketamine induced general anaesthesia.
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@#AIM: To assess the neuroprotective effect of bis(7)-tacrine in experimental Sprague-Dawley(SD)rat glaucoma.<p>METHODS: Totally 24 rats were randomly divided into control group, operated group, 0.5mg/kg bis(7)-tacrine group and 5mg/kg memantine group. Unilateral elevation of intraocular pressure(IOP)was produced by hypertonic saline injection into an episcleral vein. Animals were orally dosed daily with bis(7)-tacrine or memantine. IOP was measured in both eyes of animals per 3d, and the number of retinal ganglion cells and the thickness of nerve fiber layer axon bundle were measured at 5wk.<p>RESULTS: Elevated IOP were induced in 3 glaucoma groups. Compared with control group, the retinal ganglion cells decreased from 119.50±8.26 to 79.83±9.58 and the thickness of axon bundle come down from 13.40±0.60 μm to 6.64±0.50 μm in operated group. However the number of the retinal ganglion cells was 109.00±7.04 in bis(7)-tacrine group and 107.33±8.57 in memantine group individually. The thickness of axon bundle was 12.26±0.78μm in bis(7)-tacrine group and 10.13±1.19μm in memantine group individually.<p>CONCLUSION: Both bis(7)-tacrine and memantine inhibited retinal ganglion cells loss, but only bis(7)-tacrine decreased the thickness declining of axon bundle.
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@#AIM: To assess the neuroprotective effect of bis(7)-tacrine in experimental Sprague-Dawley(SD)rat glaucoma.<p>METHODS: Totally 24 rats were randomly divided into control group, operated group, 0.5mg/kg bis(7)-tacrine group and 5mg/kg memantine group. Unilateral elevation of intraocular pressure(IOP)was produced by hypertonic saline injection into an episcleral vein. Animals were orally dosed daily with bis(7)-tacrine or memantine. IOP was measured in both eyes of animals per 3d, and the number of retinal ganglion cells and the thickness of nerve fiber layer axon bundle were measured at 5wk.<p>RESULTS: Elevated IOP were induced in 3 glaucoma groups. Compared with control group, the retinal ganglion cells decreased from 119.50±8.26 to 79.83±9.58 and the thickness of axon bundle come down from 13.40±0.60 μm to 6.64±0.50 μm in operated group. However the number of the retinal ganglion cells was 109.00±7.04 in bis(7)-tacrine group and 107.33±8.57 in memantine group individually. The thickness of axon bundle was 12.26±0.78μm in bis(7)-tacrine group and 10.13±1.19μm in memantine group individually.<p>CONCLUSION: Both bis(7)-tacrine and memantine inhibited retinal ganglion cells loss, but only bis(7)-tacrine decreased the thickness declining of axon bundle.
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Abstract Objective Schizophrenia is a complex and chronic psychiatric disorder. In recent years, studies have found glutamatergic system participation in its etiopathogenesis, especially through aberrant NMDA receptors functioning. Thus, drugs that modulate this activity, as amantadine and memantine, could theoretically be used in its treatment. To perform a systematic literature review about memantine and amantadine use as adjunct in schizophrenia treatment. Methods A systematic review of papers published in English indexed in the electronic database PubMed ® using the terms "memantine", "amantadine" and "schizophrenia" published until October 2016. Results We found 144 studies, 8 selected for analysis due to meet the objectives of this review. Some of these have shown benefits from such drug use, especially in symptoms measured by PANSS and its subdivisions, while others do not. Discussion: The data in the literature about these drugs use for schizophrenia treatment is still limited and have great heterogeneity. Thus, assay with greater robustness are needed to assess real benefits of these drugs as adjuvant therapy.
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Humanos , Esquizofrenia/tratamento farmacológico , Amantadina/uso terapêutico , Memantina/uso terapêutico , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Placebos , Escalas de Graduação Psiquiátrica , Antipsicóticos/uso terapêutico , Amantadina/efeitos adversos , Memantina/efeitos adversos , Método Duplo-Cego , Resultado do Tratamento , PubMed , Adjuvantes Anestésicos/uso terapêuticoRESUMO
Background: Glutamate modulators are having immense potential and are newer entities for treating drug resistant depression. The objectives were to generate statistical evidence on basis of existing data of ketamine, memantine, riluzole and d-cycloserine in resistant depression.Methods: A total of 14 RCTs following PRISMA guidelines and matching inclusion and exclusion criteria were collected of ketamine (5), memantine (3), riluzole (2) and d-cycloserine (4) vs placebo in drug resistant depression. Only RCTs with primary diagnosis of drug resistant depression (Previously on two standard antidepressant therapy) were included. Studies with treatment response rate, 50% reduction in total score of the depression rating scale-Montgomery-Åsberg Depression Rating Scale or the Hamilton Depression Rating Scale or Beck Depression Inventory was chosen as clinical outcome measure. RevMan 5.3 software was used for the analysis.Results: In ketamine group using random effect model SMD was 2.122 (95% CI 0.659-3.584). P-value was statistically significant (random effect p <0.005 and in fixed effect <0.001). In memantine group, using random effect model -0.963 was SMD and (95% CI -1.958-0.0324). P-value was <0.001, significant in fixed effect. In riluzole group, SMD was -0.564 with (95% CI -3.927-2.799) in random effect. P-value was 0.741. In d-cycloserine group SMD was 0.316 with (95% CI -1.252-1.885) in random effect. P-value was 0.690.Conclusions: Ketamine showed best efficacy followed by memantine. Riluzole and DCS as such have no efficacy although its acts by same glutamate pathway. More molecular based research is required in use of glutamate modulators in resistant depression.
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Memantine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, suppresses the release of excessive levels of glutamate that may induce neuronal excitation. Here we investigated the effects of memantine on salicylate-induced tinnitus model. The expressions of the activity-regulated cytoskeleton-associated protein (ARC) and tumor necrosis factor-alpha (TNF α)genes; as well as the NMDA receptor subunit 2B (NR2B) gene and protein, were examined in the SH-SY5Y cells and the animal model. We also used gap-prepulse inhibition of the acoustic startle reflex (GPIAS) and noise burst prepulse inhibition of acoustic startle, and the auditory brainstem level (electrophysiological recordings of auditory brainstem responses, ABR) and NR2B expression level in the auditory cortex to evaluate whether memantine could reduce salicylate-mediated behavioral disturbances. NR2B was significantly upregulated in salicylate-treated cells, but downregulated after memantine treatment. Similarly, expression of the inflammatory cytokine genes TNFα and immediate-early gene ARC was significantly increased in the salicylate-treated cells, and decreased when the cells were treated with memantine. These results were confirmed by NR2B immunocytochemistry. GPIAS was attenuated to a significantly lesser extent in rats treated with a combination of salicylate and memantine than in those treated with salicylate only. The mean ABR threshold in both groups was not significant different before and 1 day after the end of treatment. Additionally, NR2B protein expression in the auditory cortex was markedly increased in the salicylate-treated group, whereas it was reduced in the memantine-treated group. These results indicate that memantine is useful for the treatment of salicylate-induced tinnitus.
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Animais , Ratos , Acústica , Córtex Auditivo , Tronco Encefálico , Potenciais Evocados Auditivos do Tronco Encefálico , Genes Precoces , Ácido Glutâmico , Imuno-Histoquímica , Integrina alfa2 , Memantina , Modelos Animais , N-Metilaspartato , Neurônios , Ruído , Inibição Pré-Pulso , Reflexo de Sobressalto , Zumbido , Fator de Necrose Tumoral alfaRESUMO
Memantine is a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist clinically approved for moderate-to-severe Alzheimer's disease (AD) to improve cognitive functions. There is no report about the proteomic alterations induced by memantine in AD mouse model yet. In this study, we investigated the protein profiles in the hippocampus and the cerebral cortex of AD-related transgenic mouse model (3×Tg-AD) treated with memantine. Mice (8-month) were treated with memantine (5 mg/kg/bid) for 4 months followed by behavioral and molecular evaluation. Using step-down passive avoidance (SDA) test, novel object recognition (NOR) test and Morris water maze (MWM) test, it was observed that memantine significantly improved learning and memory retention in 3xTg-AD mice. By using quantitative proteomic analysis, 3301 and 3140 proteins in the hippocampus and the cerebral cortex respectively were identified to be associated with AD abnormalities. In the hippocampus, memantine significantly altered the expression levels of 233 proteins, among which PCNT, ATAXIN2, TNIK, and NOL3 were up-regulated, and FLNA, MARK 2 and BRAF were down-regulated. In the cerebral cortex, memantine significantly altered the expression levels of 342 proteins, among which PCNT, PMPCB, CRK, and MBP were up-regulated, and DNM2, BRAF, TAGLN 2 and FRY1 were down-regulated. Further analysis with bioinformatics showed that memantine modulated biological pathways associated with cytoskeleton and ErbB signaling in the hippocampus, and modulated biological pathways associated with axon guidance, ribosome, cytoskeleton, calcium and MAPK signaling in the cerebral cortex. Our data indicate that memantine induces higher levels of proteomic alterations in the cerebral cortex than in the hippocampus, suggesting memantine affects various brain regions in different manners. Our study provides a novel view on the complexity of protein responses induced by memantine in the brain of AD.
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Animais , Camundongos , Doença de Alzheimer , Axônios , Encéfalo , Cálcio , Córtex Cerebral , Cognição , Biologia Computacional , Citoesqueleto , Hipocampo , Aprendizagem , Memantina , Memória , Camundongos Transgênicos , N-Metilaspartato , Proteoma , Ribossomos , ÁguaRESUMO
Objective@#To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.@*Methods@#Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table, the patients were divided into the observation group and the control group, with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin, and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score, oxidative stress index, inflammatory factor, cerebral kinetic index changes, clinical efficacy and adverse reactions after treatment were compared between the two groups.@*Results@#The therapeutic effect of the observation group was 87.88%(29/33), which was significantly higher than 63.64%(21/33) of the control group (χ2=5.280, P=0.022). After treatment, the ADL, MoCA, SOD levels, Vmax and BHI of the observation group were (41.26±5.37)points , (24.23±1.71)points, (112.27±15.35)μU/L, (65.15±11.75)cm/s, (0.79±0.36), respectively, which were higher than those of the control group [(36.19±4.07)points, (20.25±1.46)points, (93.84±12.76)μU/L, (59.15±11.74)cm/s, (0.58±0.26)], the differences were statistically significant (t=4.322, 10.168, 5.304, 2.075, 2.846, all P<0.05). The levels of MDA, HCy, TNF-α, IL-6 and IL-1β in the observation group were (6.37±1.05)μmol/L, (31.36±9.59)μmol/L, (184.15±15.12)ng/L, (229.85±27.69)ng/L, (127.64±17.86)ng/L, respectively, which were lower than those in the control group [(7.32±1.07)μmol/L, (42.27±11.34)μmol/L, (208.72±15.26)ng/L, (262.75±25.64)ng/L, (148.75±18.64)ng/L], the differences were statistically significant (t=3.640, 4.220, 6.570, 5.008, 4.698, all P<0.05). There was no statistically significant difference in the incidence of adverse reactions between the two groups (P>0.05).@*Conclusion@#The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response, improve cerebral hemodynamics and cognitive function, and improve patients’ quality of life.
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Objective: To investigate the effect of memantine on Parkinson's disease cell models. Methods: Parkinson's disease cell models were established using PC12 cells incubated with 6-hydroxydopamine (6-OHDA). Flow cytometry and microscopy were used to investigate the apoptotic process and the percentage of different apoptotic stages. PC12 cells were infected with lentiviral vectors to knockdown Nur77. Western blotting was used to detect the expression of Nur77 and caspase -3, -8, -9, -12 in PC12 cells withdifferent concentrations of 6-OHDA or 6-OHDA+memantine. Results: 6-OHDA led to apoptosis PC12 cells, and increased the expression of Nur77 and caspases. Memantine significantly inhibited 6-OHDA-induced apoptosis of PC12 cells. Meanwhile, memantine could mitigate apoptosis of PC12 cells by regulating the Nur77 and caspase pathway. Conclusions: Memantine has a protective effect on the PC12 cell model via regulating the Nur77 and caspases pathway.
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Objective To investigate the efficacy and safety of rosuvastatin combined with memantine hydrochloride in the treatment of vascular dementia.Methods Sixty-six patients with vascular dementia admitted to the Hospital of Zhejiang Provincial Armed Police Force and Haining Kanghua Hospital from January 2016 to January 2018 were enrolled.According to the digital table,the patients were divided into the observation group and the control group,with 33 cases in each group.Both two groups were given routine treatment.The control group was treated with rosuvastatin,and the observation group was given rosuvastatin combined with memantine hydrochloride.Both two groups were treated for 12 weeks.The ADL score and MoCA score,oxidative stress index,inflammatory factor,cerebral kinetic index changes,clinical efficacy and adverse reactions after treatment were compared between the two groups.Results The therapeutic effect of the observation group was 87.88％ (29/33),which was significantly higher than 63.64％ (21/33) of the control group (x2 =5.280,P =0.022).After treatment,the ADL,MoCA,SOD levels,Vmax and BHI of the observation group were (41.26 ± 5.37) points,(24.23 ± 1.71) points,(112.27 ± 15.35) μU/L,(65.15 ± 11.75) cm/s,(0.79 ± 0.36),respectively,which were higher than those of the control group [(36.19 ± 4.07) points,(20.25 ± 1.46) points,(93.84 ± 12.76) μU/L,(59.15 ± 11.74) cm/s,(0.58 ± 0.26)],the differences were statistically significant (t =4.322,10.168,5.304,2.075,2.846,all P ＜ 0.05).The levels of MDA,HCy,TNF-α,IL-6 and IL-1β in the observation group were (6.37 ± 1.05) μmol/L,(31.36 ± 9.59) μmol/L,(184.15 ± 15.12) ng/L,(229.85 ± 27.69) ng/L,(127.64 ± 17.86) ng/L,respectively,which were lower than those in the control group [(7.32 ± 1.07) μmol/L,(42.27 ± 11.34) μmol/L,(208.72 ± 15.26) ng/L,(262.75 ± 25.64) ng/L,(148.75 ± 18.64) ng/L],the differences were statistically significant (t =3.640,4.220,6.570,5.008,4.698,all P ＜ 0.05).There was no statistically significant difference in the incidence of adverse reactions between the two groups (P ＞ 0.05).Conclusion The clinical efficacy of rosuvastatin combined with memantine hydrochloride in the treatment of patients with vascular dementia can significantly reduce oxidative stress and inflammatory response,improve cerebral hemodynamics and cognitive function,and improve patients' quality of life.
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Objective: To investigate the effect of memantine on Parkinson's disease cell models. Methods: Parkinson's disease cell models were established using PC12 cells incubated with 6-hydroxydopamine (6-OHDA). Flow cytometry and microscopy were used to investigate the apoptotic process and the percentage of different apoptotic stages. PC12 cells were infected with lentiviral vectors to knockdown Nur77. Western blotting was used to detect the expression of Nur77 and caspase -3, -8, -9, -12 in PC12 cells withdifferent concentrations of 6-OHDA or 6-OHDA+memantine. Results: 6-OHDA led to apoptosis PC12 cells, and increased the expression of Nur77 and caspases. Memantine significantly inhibited 6-OHDA-induced apoptosis of PC12 cells. Meanwhile, memantine could mitigate apoptosis of PC12 cells by regulating the Nur77 and caspase pathway. Conclusions: Memantine has a protective effect on the PC12 cell model via regulating the Nur77 and caspases pathway.
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OBJECTIVE: To synthesize the available evidence and state of the art of economic evaluations which evaluate the use of memantine, whether alone or combined with donepezil, for moderate to severe Alzheimer's disease (AD), focusing on the analytical decision models built. METHOD: The electronic databases MEDLINE, EMBASE, NHS EED, CEA Registry and LILACS were searched for references. After duplicates were removed, two independent reviewers evaluated the titles and abstracts and subsequently the full texts. The Drummond M. tool was used to evaluate the quality of the studies. RESULTS: After the application of the eligibility criteria, twelve complete economic evaluations were included. One evaluation was a clinical trial, two involved simulations and nine used Markov models. The main outcome measure adopted was dominated by cost per quality adjusted life year (QALY). The use of memantine was considered cost-effective and dominant in eight studies; while in a single study, its use was dominated when compared to donepezil for moderate AD. Sensitivity analyzes were systematically performed, with robust results. The quality assessment indicated that the methodological quality of the studies was good. CONCLUSION: Although there is some controversy regarding the benefits derived from the use of memantine, whether combined or not with donepezil, the evidence collected suggests that it is cost-effective in the countries where the studies were performed. However, local economic studies need to be performed, given the significant variability derived from the different parameters adopted in the evaluations.
OBJETIVO: Sintetizar as evidências disponíveis e o estado da arte das avaliações econômicas que avaliaram a memantina isolada ou combinada com donepezil para a Doença de Alzheimer (DA) moderada a grave, com foco nos modelos de decisão analíticos elaborados. MÉTODO: As bases eletrônicas MEDLINE, EMBASE, NHS EED, CEA Registry e LILACS foram usadas para busca de referências. Após a remoção de duplicatas, dois revisores independentes avaliaram os títulos e resumos e, posteriormente, os textos completos. A ferramenta de Drummond M. foi utilizada para avaliação da qualidade dos estudos. RESULTADO: Após a aplicação dos critérios de elegibilidade, foram incluídas doze avaliações econômicas completas. Quanto aos desenhos de estudo, uma avaliação foi conduzida ao longo de ensaio clínico, duas fizeram simulação e nove utilizaram modelos de Markov. A principal medida de desfecho adotada foi custo por ano de vida ajustado por qualidade (QALY). O uso da memantina foi considerada custo-efetivo e dominante em oito estudos; em um único estudo, seu uso foi dominado quando comparado ao donepezil para a DA moderada. Análises de sensibilidade foram sistematicamente realizadas, evidenciando resultados robustos. A avaliação de qualidade apontou boa qualidade metodológica dos trabalhos. CONCLUSÃO: Apesar de existirem controvérsias quanto aos benefícios derivados do uso da memantina associada ou não ao donepezil, o levantamento das evidências sugere que ela é custo-efetiva nos países onde os estudos foram elaborados. No entanto, estudos econômicos locais necessitam ser realizados, dada a grande variabilidade derivada dos diferentes parâmetros adotados nas avaliações.
Assuntos
Humanos , Idoso , Idoso de 80 Anos ou mais , Memantina , Revisão , Custos e Análise de Custo , Doença de AlzheimerRESUMO
Dementia is a clinical syndrome characterized by a cluster of symptoms and signs that manifest as difficulties in cognitive functions such as memory, psychological and psychiatric changes, and impairments in activities of daily living. As a result of worldwide trends of population aging, dementia has had a huge impact on public health in almost all countries. Disease modification therapies for dementia have not yet been developed. However, pharmacotherapy is essential in patients with dementia to combat delays in their cognitive and functional decline. In this article, we review the current pharmacotherapy for dementia. Three acetylcholinesterase inhibitors—donepezil, rivastigmine, galantamine—and memantine are the only medications that have been approved for the treatment of dementia. We present the indications, dose recommendations, side effects, and criteria for National Health Insurance coverage in Korea of these medications for dementia treatment. Although the Ministry of Food and Drug Safety in Korea has not approved any medications for managing the behavioral and psychological symptoms of dementia, some antipsychotics and antidepressants have been studied and used clinically for those purposes. Clinicians may consider vitamin E, Ginkgo biloba extract, choline alfoscerate, or omega-3 fatty acids as additional treatment options. Non-steroid anti-inflammatory drugs, estrogen hormone therapy, and statins are not generally recommended for dementia treatment. We believe that our findings will aid clinicians in the treatment of patients with cognitive decline.