Dementia medications and risk of falls, syncope, and related adverse events: meta-analysis of randomized controlled trials

OBJECTIVES: To evaluate the effect of cholinesterase inhibitors (ChEIs) and memantine on the risk of falls, syncope, and related events, defined as fracture and accidental injury. DESIGN: Meta‐analysis of randomized controlled trials that were identified from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (no language restriction, through July 2009), and manual search. SETTING: Community and nursing homes. PARTICIPANTS: Participants in fifty‐four placebo‐controlled randomized trials and extension studies of ChEIs and memantine that reported falls, syncope, and related events in cognitively impaired older adults. MEASUREMENTS: Falls, syncope, fracture, and accidental injury. RESULTS: ChEI use was associated with greater risk of syncope (odds ratio (OR)=1.53, 95% confidence interval (CI)=1.02–2.30) than placebo but not with other events (falls: OR=0.88, 95% CI=0.74–1.04; fracture: OR=1.39, 95% CI=0.75–2.56; accidental injury: OR=1.13, 95% CI=0.87–1.45). Memantine use was associated with fewer fractures (OR=0.21, 95% CI=0.05–0.85) but not with other events (falls: OR=0.92, 95% CI=0.72–1.18; syncope: OR=1.04, 95% CI=0.35–3.04; accidental injury: OR=0.80, 95% CI=0.56–1.12). There was no differential effect according to type and severity of cognitive impairment, residential status, or length of follow‐up, although because of underreporting and small number of events, a potential benefit or risk cannot be excluded. CONCLUSION: ChEIs may increase the risk of syncope, with no effects on falls, fracture, or accidental injury in cognitively impaired older adults. Memantine may have a favorable effect on fracture, with no effects on other events. More research is needed to confirm the reduction in fractures observed for memantine.     

美金刚对大鼠脑缺血再灌注后Caspase-3表达及丙二醛含量的影响

目的:观察非竞争性NMDA受体拮抗剂美金刚对大鼠脑缺血再灌注后迟发性脑损伤的抑制作用.方法:雄性Wistar大鼠135只,随机分为假手术组、模型组及干预组,采用线栓法建立大鼠大脑中动脉闭塞(MCAO)局灶性脑缺血再灌注模型,干预组用美金刚溶液灌胃,HE染色观察神经元形态变化,免疫组织化学染色检测神经元Caspase-3...     

Rivastigmine monotherapy and combination therapy with memantine in patients with moderately severe Alzheimer's disease who failed to benefit from previous cholinesterase inhibitor treatment

We investigated the efficacy and safety of rivastigmine alone and combined with memantine in Alzheimer's disease patients previously failing on donepezil or galantamine. This was a prospective, open-label, multicentre study. After stopping donepezil or galantamine, patients received rivastigmine 3-12 mg/day for 16 weeks. Non-responders to rivastigmine monotherapy at week 16 received memantine 5-20 mg/day plus rivastigmine for 12 weeks. The primary efficacy parameter was response (Mini-Mental State Examination equal or better than at week 16) to dual therapy at week 28. Secondary criteria were changes on cognitive and behavioural scales. Two hundred and two patients were included. Ninety-three (46.3%) patients responded to rivastigmine monotherapy. Of 86 patients receiving additional memantine for another 12 weeks, 67 (77.9%) responded. Combination therapy caused no apparent safety concerns. When patients fail on donepezil or galantamine, switching to rivastigmine may improve cognition and behaviour. Should they continue to deteriorate, the addition of memantine may be beneficial.     

美金刚的临床应用现状及进展

盐酸美金刚临床主要用于治疗中、重度阿尔茨海默病和血管性痴呆,可改善临床症状,延缓疾病进展,提高病人的生活质量。随着更多深入的临床试验研究,目前有很多美金刚应用于其他方面治疗的报道。无论长期还是短期应用,美金刚都是安全和相对经济的一种选择。     

针刺联合盐酸关金刚改善中风后失语临床观察

目的：观察针刺联合盐酸美金刚治疗中风后失语的临床疗效.方法：将62例中风失语症患者随机分为针刺联合盐酸美金刚治疗组（31例）和单纯针刺治疗组（31例）,盐酸羡金刚初始剂量5 mg/天,1周后增至10 mg/天;针刺治疗选“醒脑开窍”针刺法结合金津、玉液舌下点刺出血,分别观察两组治疗前后“汉语失语症检查法”评分及两组之间疗效比较.结果：治疗组总有效率为93.55％（95％ CI=78.55％～99.20％）;对照组为68.97％ （95％ CI =52.12％～ 85.81％）,两组综合疗效比较（u=2.990 2,P=0.004 8）;治疗组较对照组可明显提高患者的语言积分参数（t=13.147 1,P＜0.01）.结论：针刺联合盐酸美金刚治疗中风后失语的临床疗效优于单纯针刺疗法,其收益为OR =0.15（95％ CI =0.03 ～0.80）,NNT =4（95％ CI=2.26～20.04）.     

Effects of memantine on mania-like phenotypes exhibited by Drosophila Shaker mutants

Introduction

Increased glutamate levels and electrolytic fluctuations have been observed in acutely manic patients. Despite some efficacy of the non-competitive NMDA receptor antagonist memantine (Mem), such as antidepressant-like and mood-stabilizer drugs in clinical studies, its specific mechanisms of action are still uncertain. The present study aims to better characterize the Drosophila melanogaster fly Shaker mutants (SH), as a translational model of manic episodes within bipolar disorder in humans, and to investigate the potential anti-manic properties of Mem.

Methods and Results

Our findings showed typical behavioral abnormalities in SH, which mirrored with the overexpression of NMDAR-NR1 protein subunit, matched well to glutamate up-regulation. Such molecular features were associated to a significant reduction of SH brain volume in comparison to Wild Type strain flies (WT). Here we report on the ability of Mem treatment to ameliorate behavioral aberrations of SH (similar to that of Lithium), and its ability to reduce NMDAR-NR1 over-expression.

Conclusions

Our results show the involvement of the glutamatergic system in the SH, given the interaction between the Shaker channel and the NMDA receptor, suggesting this model as a promising tool for studying the neurobiology of bipolar disorders. Moreover, our results show Mem as a potential disease-modifying therapy, providing insight on new mechanisms of action.     

美金刚联合脑电磁治疗阿尔茨海默病痴呆的行为精神症状的疗效观察

目的 探讨美金刚联合脑电磁治疗阿尔茨海默病(AD)痴呆的行为精神症状(BPSD)的研究.方法 选取2017年1月—2020年1月在浙江省人民医院就诊的AD伴BPSD患者122例,按照随机表法分为观察组和对照组,各61例.对照组口服美金刚片;观察组在对照组基础上结合脑电磁治疗.两组疗程均为12周.比较两组疗效,以及治疗前...