Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health prob...Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health problem.展开更多
Lycorine and galantamine are natural alkaloids found in Amaryllidaceae plants, such as narcissus. Narcissus leaves and roots are sometimes accidentally ingested because they resemble vegetables. Lycorine and galantami...Lycorine and galantamine are natural alkaloids found in Amaryllidaceae plants, such as narcissus. Narcissus leaves and roots are sometimes accidentally ingested because they resemble vegetables. Lycorine and galantamine are toxic and cause such effects as nausea, vomiting, and abdominal pain, when accidentally ingested. In a case of narcissus poisoning, the detection of lycorine and galantamine in biological samples is vital to determine whether they have been ingested. This study establishes a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to measure the lycorine and galantamine content of human serum, which can be used for mild to fatal poisoning cases. A serum pretreatment procedure was performed using acetonitrile and QuEChERS AOAC powder. The separation of the compounds was conducted using a pentafluorophenyl column, CAPCELL CORE PFP (2.1 mm I.D. × 100 mm, 2.7 μm). Lycorine, galantamine, and galantamine-d<sub>6</sub> (internal standard) were identified by the transitions of m/z 288 → 147, m/z 288 → 213, and m/z 294 → 216, respectively. The calibration curves were linear in the ranges of 0.05 to 5 ng/mL and 5 to 100 ng/mL, with R<sup>2</sup> > 0.999. The precision and accuracy were within the permissible range. The matrix effects of lycorine and galantamine were 94.3% - 98.4% and 87.8% - 91.1%, respectively. The extraction recovery rates of lycorine and galantamine were 101.9% - 112.7% and 95.6% - 107.1%, respectively. The present method detected lycorine and galantamine in the sera of three patients with mild poisoning that had accidentally ingested. This method is applicable in cases of lycorine and galantamine poisoning.展开更多
Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascul...Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.展开更多
Huntington's disease(HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cog...Huntington's disease(HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington's disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington's disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.展开更多
Current treatment paradigm in Alzheimer’s disease(AD)involves multiple approaches combining pharmacological and nonpharmacological intervention to mitigate the clinical symptoms,slow the progressive loss of cognitive...Current treatment paradigm in Alzheimer’s disease(AD)involves multiple approaches combining pharmacological and nonpharmacological intervention to mitigate the clinical symptoms,slow the progressive loss of cognitive and functional abilities,or modify the disease course.So far,beyond anti-cholinesterase inhibitors(ACh EIs),donepezil,rivastigmine,galantamine,and antagonist of N-methyl-D-aspartic acid(NMDA)receptor,there are no newly approved medicines to treat AD.Under pharmacological treatment,the personal characteristic and the intra-individual therapeutic evaluations to examine various cognitive domains,behavioral and psychological problems,and global function should be considered when choosing any of ACh EIs.The use of optimal dosage referring to the expected clinical outcomes and currently reported deficits from patient with AD has become an important issue in clinical treatment.Establishing and maintaining a strong therapeutic alliance to physician,patient,and caregiver is crucial and central to the comprehensive care in AD.展开更多
基金supported by the Brazilian funding agencies:CNPq(Conselho Nacional de Desenvolvimento Científico e Tecnológico)CAPES(Coordenacao de Aperfeicoamento de Pessoal de Nível Superior)-No:5614112Student Agreement Program for post graduation–PEC-PG.
文摘Alzheimer’s disease（AD）is the most common type of dementia in elderly population.With a growing aging population not only in the United States but also in the worldwide,AD constitutes an emergent public health problem.
文摘Lycorine and galantamine are natural alkaloids found in Amaryllidaceae plants, such as narcissus. Narcissus leaves and roots are sometimes accidentally ingested because they resemble vegetables. Lycorine and galantamine are toxic and cause such effects as nausea, vomiting, and abdominal pain, when accidentally ingested. In a case of narcissus poisoning, the detection of lycorine and galantamine in biological samples is vital to determine whether they have been ingested. This study establishes a liquid chromatography-tandem mass spectrometry (LC/MS/MS) method to measure the lycorine and galantamine content of human serum, which can be used for mild to fatal poisoning cases. A serum pretreatment procedure was performed using acetonitrile and QuEChERS AOAC powder. The separation of the compounds was conducted using a pentafluorophenyl column, CAPCELL CORE PFP (2.1 mm I.D. × 100 mm, 2.7 μm). Lycorine, galantamine, and galantamine-d<sub>6</sub> (internal standard) were identified by the transitions of m/z 288 → 147, m/z 288 → 213, and m/z 294 → 216, respectively. The calibration curves were linear in the ranges of 0.05 to 5 ng/mL and 5 to 100 ng/mL, with R<sup>2</sup> > 0.999. The precision and accuracy were within the permissible range. The matrix effects of lycorine and galantamine were 94.3% - 98.4% and 87.8% - 91.1%, respectively. The extraction recovery rates of lycorine and galantamine were 101.9% - 112.7% and 95.6% - 107.1%, respectively. The present method detected lycorine and galantamine in the sera of three patients with mild poisoning that had accidentally ingested. This method is applicable in cases of lycorine and galantamine poisoning.
基金supported by the Natural Science Foundation of Liaoning Province of China,No.20170541036(to HYL)
文摘Objective: To assess and compare the clinical efficacy and safety of cognitive enhancers(donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and global status in patients with vascular cognitive impairment.Data sources: The initial literature search was performed with PubMed, EMBASE, the Cochrane Methodology Register, the Cochrane Central Register of Controlled Trials, and Cumulative Index to Nursing & Allied Health(CINAHL) from inception to January 2018 for studies regarding donepezil, galantamine, rivastigmine, and memantine for treatment of vascular cognitive impairment.Data selection: Randomized controlled trials on donepezil, galantamine, rivastigmine, and memantine as monotherapy in the treatment of vascular cognitive impairment were included. A Bayesian network meta-analysis was conducted. Outcome measures: Efficacy was assessed by changes in scores of the Alzheimer's Disease Assessment Scale, cognitive subscale, Mini-Mental State Examination, Neuropsychiatric Inventory scores and Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input, Activities of Daily Living, the Clinical Dementia Rating scale. Safety was evaluated by mortality, total adverse events(TAEs), serious adverse events(SAEs), nausea, vomiting. diarrhea, or cerebrovascular accidents(CVAs). Results: After screening 1717 citations, 12 randomized controlled trials were included. Donepezil and rivastigmine(mean difference(e) = –0.77, 95% confidence interval(CI): 0.25–1.32; MD = 1.05, 95% CI: 0.18–1.79) were significantly more effective than placebo in reducing Mini-Mental State Examination scores. Donepezil, galantamine, and memantine(MD = –1.30, 95% CI: –2.27 to –0.42; MD = –1.67, 95% CI: –3.36 to –0.06; MD = –2.27, 95% CI: –3.91 to –0.53) showed superior benefits on the Alzheimer's Disease Assessment Scale–cognitive scores compared with placebo. Memantine(MD = 2.71, 95% CI: 1.05–7.29) improved global status(Clinician's Interview-Based Impression of Change Scale Plus Caregiver's Input) more than the placebo. Safety results revealed that donepezil 10 mg(odds ratio(OR) = 3.04, 95% CI: 1.86–5.41) contributed to higer risk of adverse events than placebo. Galantamine(OR = 5.64, 95% CI: 1.31–26.71) increased the risk of nausea. Rivastigmine(OR = 16.80, 95% CI: 1.78–319.26) increased the risk of vomiting. No agents displayed a significant risk of serious adverse events, mortality, cerebrovascular accidents, or diarrhea.Conclusion: We found significant efficacy of donepezil, galantamine, and memantine on cognition. Memantine can provide significant efficacy in global status. They are all safe and well tolerated.
文摘Huntington's disease(HD) is a neurodegenerative disease associated with cognitive deficits. Cognitive dysfunction may be present in the early stages of the disease, even before the onset of motor symptoms. The cognitive dysfunction includes executive dysfunction, psychomotor symptoms, visuospatial deficits, perceptual deficits, memory loss and difficulty learning new skills. Acetylcholinesterase inhibitors have shown good effect in the treatment of other types of dementia and it is postulated that it might delay cognitive decline in HD. We reviewed the evidence for Acetylcholinesterase inhibitors in the treatment of cognitive decline and dementia associated with Huntington's disease. We identified 6 articles that investigated the role of Acetylcholinesterase inhibitors for treatment of cognitive deficits in Huntington's disease. Following the review, the authors concluded that there is limited evidence for the use of Acetylcholinesterase inhibitors for cognitive impairment in HD.
基金the support by Neuroscience Research Center,Kaohsiung Medical University,KMU-TC108B01.
文摘Current treatment paradigm in Alzheimer’s disease(AD)involves multiple approaches combining pharmacological and nonpharmacological intervention to mitigate the clinical symptoms,slow the progressive loss of cognitive and functional abilities,or modify the disease course.So far,beyond anti-cholinesterase inhibitors(ACh EIs),donepezil,rivastigmine,galantamine,and antagonist of N-methyl-D-aspartic acid(NMDA)receptor,there are no newly approved medicines to treat AD.Under pharmacological treatment,the personal characteristic and the intra-individual therapeutic evaluations to examine various cognitive domains,behavioral and psychological problems,and global function should be considered when choosing any of ACh EIs.The use of optimal dosage referring to the expected clinical outcomes and currently reported deficits from patient with AD has become an important issue in clinical treatment.Establishing and maintaining a strong therapeutic alliance to physician,patient,and caregiver is crucial and central to the comprehensive care in AD.
