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Frontiers in Pharmacology 2020Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these...
BACKGROUND
Pharmacological treatments play a significant role in treating mild to moderate Alzheimer's disease (AD), but the optimal doses of various drugs used for these treatments are unknown. Our study compared the efficacy, acceptability, and safety of different doses of pharmacological treatments for mild to moderate AD.
METHODS
Randomized controlled trials (RCTs) were identified by searching the PubMed, EMBASE, and Cochrane Library databases (all RCTs published from the date of inception of the databases until September 19, 2019). Trials comparing the efficacy, acceptability, and safety of pharmacological interventions involving donepezil, galantamine, rivastigmine, memantine, huperzine A, and extract EGb761, alone or in combination, were identified. The primary outcomes were efficacy, acceptability, and safety.
RESULTS
Our meta-analysis included 37 studies involving 14,705 participants. In terms of improving cognitive function, galantamine 32 mg, galantamine 24 mg, donepezil 5 mg, and donepezil 10 mg were more effective than other interventions, with the surface under the cumulative ranking curve (SUCRA) values of 93.2, 75.5, 73.3, and 65.6%, respectively. According to the SUCRA values, EGb761 240 mg was considered to be the optimal intervention in terms of both acceptability and safety. With regard to clinical global impression, rivastigmine 12 mg had the highest probability of being ranked first (83.7%). The rivastigmine 15 cm patch (SUCRA = 93.7%) may be the best choice for daily living. However, there were no interventions that could significantly improve neuropsychiatric symptoms, compared with the placebo.
CONCLUSIONS
Different doses of the tested pharmacological interventions yielded benefits with regard to cognition, acceptability, safety, function, and clinical global impressions, but not effective behaviors.
PubMed: 32528296
DOI: 10.3389/fphar.2020.00778 -
Neurological Sciences : Official... Oct 2020Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease... (Review)
Review
INTRODUCTION
Improvement of cognitive function may be desirable for healthy individuals and clinically beneficial for those with cognitive impairment such as from Alzheimer's disease (AD) or mild cognitive impairment (MCI). The aim of this systematic review is to investigate the cognitive effects of oral saffron intake, in patients with MCI/AD and/or in non-demented individuals, by following the PRISMA guidelines.
METHODS
We performed a literature search on MedLine, Cochrane library, and ClinicalTrials.gov to identify randomized controlled trials (RCTs) investigating the effects of oral saffron administration in patients with MCI/AD and/or in non-demented individuals.
RESULTS
Five studies (enrolling 325 individuals) met our inclusion criteria. Four studies included patients with MCI/AD, and one study included cognitively normal individuals. Saffron was well-tolerated in all groups. Regarding cognitively impaired patients, scores on Alzheimer's Disease Assessment Scale-cognitive subscale or Mini mental state examination were significantly better when saffron was compared with placebo and did not differ significantly when saffron was compared with donepezil or memantine. Saffron effects on functional status were similar with its effects on cognition.
CONCLUSIONS
Saffron was shown to be equally effective to common symptomatic drugs for MCI/AD and resulted in no difference in the incidence of side effects, when compared with placebo or drugs. The promising results should be seen cautiously, since the evidence was derived from studies with potentially high risk of bias (ROB). RCTs with larger sample sizes and low ROB are required to definitively assess the potential role of saffron as an MCI/AD treatment.
Topics: Alzheimer Disease; Cognition; Cognitive Dysfunction; Crocus; Donepezil; Humans
PubMed: 32445136
DOI: 10.1007/s10072-020-04427-0 -
Frontiers in Aging Neuroscience 2020The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture...
The effects of acupuncture on Alzheimer's disease (AD) outcomes remain controversial. The aim of this review was to evaluate the effectiveness and safety of acupuncture for the treatment of AD. PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, VIP Database for Chinese Technical Periodicals, China National Knowledge Infrastructure, and Wanfang Data were searched to identify relevant randomized controlled trials from inception to January 19, 2019. Data were extracted and evaluated by two authors independently. The data analysis was conducted using R (version 3.6.0) and RStudio (version 1.2.1335) software. Thirty trials involving 2,045 patients were included. Acupuncture plus drug therapy may have been more beneficial for general cognitive function in AD patients than drug therapy alone (short-term treatment: MD, mean difference = 1.94, 95% CI: 1.11, 2.77; < 0.01; medium-term treatment: = 4.41, 95% CI: 1.83, 7.00; < 0.01). People who received acupuncture plus drug therapy attained higher ADL (Activities of Daily Living) scores than patients who received drug therapy alone for medium-term treatment duration ( = -2.14; 95% CI: -3.69, -0.59; < 0.01). However, there is no statistically significant difference in subgroup effect on MMSE (Mini-mental Status Examination) and ADLs ( > 0.05) when comparing acupuncture treatment with drug therapy (such as Donepezil hydrochloride, Nimodipine, or Yizhijiannao), or acupuncture plus drug therapy (such as Donepezil hydrochloride, Dangguishaoyaosan, or Jiannaosan) with drug therapy alone. There was also no significant difference in general cognitive function, ADLs, or incidence of adverse events between acupuncture treatment and drug therapy ( > 0.05). This review indicates that acupuncture plus drug therapy may have a more beneficial effect for AD patients than drug therapy alone on general cognitive function in the short and medium term and on ADLs in the medium term. Acupuncture alone may not have superior effects compared with drug therapy on global cognitive function, ADLs, and incidence of adverse events. Duration of treatment may not modify the effect of acupuncture in comparison with drug therapy. Additional large-scale and high-quality clinical trials are needed.
PubMed: 32435187
DOI: 10.3389/fnagi.2020.00098 -
Medicine May 2020The aim of this systematic review was to evaluate the effect of therapies for cognitive impairment on patients' perceived cognitive function in breast cancer survivors...
OBJECTIVE
The aim of this systematic review was to evaluate the effect of therapies for cognitive impairment on patients' perceived cognitive function in breast cancer survivors with chemotherapy-related cognitive impairment.
METHOD
A literature search of PubMed, Embase, and the Cochrane Library was conducted up to April 2019. Search terms included breast cancer, chemotherapy, and cognitive impairment.
RESULT
Six randomized controlled trials with a total of 305 patients were included in this review. A total of 6 randomized controlled trials using various treatments (Tibetan sound meditation, donepezil, memory and attention adaptation training, aerobic exercise, acupuncture, Qigong) for chemotherapy-related cognitive impairment met the eligibility criteria and were included. This review showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may partially improve some aspects of patients' perceived (self-reported) cognitive functioning, particularly patients' perceived cognitive impairment and ability.
CONCLUSION
In this systematic review, the results showed that meditative interventions (Tibetan sound meditation, Qigong) and cognitive therapy (memory and attention adaptation training) may be optional therapies. We hope to have more randomized controlled trials to support this result in the future.
Topics: Antineoplastic Agents; Breast Neoplasms; Cancer Survivors; Cognitive Behavioral Therapy; Cognitive Dysfunction; Female; Humans; Meditation; Randomized Controlled Trials as Topic
PubMed: 32384481
DOI: 10.1097/MD.0000000000020092 -
Medicine Jul 2019Cognitive impairment is a principal manifestation of Alzheimer disease (AD). To provide a clinical reference for the treatment of AD, a network meta-analysis (NMA) was... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cognitive impairment is a principal manifestation of Alzheimer disease (AD). To provide a clinical reference for the treatment of AD, a network meta-analysis (NMA) was performed to evaluate the effects of different anti-dementia drugs on the cognitive impairment exhibited by patients with AD.
METHODS
Relevant randomized controlled trials are found through the Pubmed database, Web of Science, Clinical Trials, Embase, Cohranne library, Chinese National Knowledge Infrastructure database, CBM databases, and Wanfang among others. A total of 33 articles were collected, with the earliest document collected having been published in February 2017. The included reports were screened for quality of papers by using strict inclusion and exclusion criteria. All analyses were based on previously published studies reporting de-identified data; thus, no ethical approval or patient consent were required. The Mini-Mental State Examination scores informed the classification of the 33 articles into a mild subgroup, which featured 11 articles, and 12 drugs (besides a placebo); a moderate subgroup, which featured 17 articles and 15 drugs (besides a placebo); and a severe subgroup, which featured 5 articles and 3 drugs (besides a placebo).
RESULTS
While donepezil, galanthamine, and huperzine demonstrated the highest efficacy in the mild cognitive dysfunction subgroup (mean difference = 5.2, 2.5, and 2.4, respectively). Donepezil, huperzine A, and rivastigmine achieved the most significant effects in the moderate cognitive dysfunction subgroup (MD = 3.8, 2.9, and 3.0 respectively). In the severe subgroup, donepezil was demonstrably superior to memantine. Donepezil was thus found to effectively address cognitive impairment in patients with AD regardless of the degrees of cognitive decline.
CONCLUSIONS
Evaluation of the clinically common anti-dementia drugs using NMA affirmed the utility of cholinesterase inhibitors, especially donepezil, in alleviating cognitive dysfunction of patients with AD. This study may therefore help to inform the clinical selection of pharmacotherapeutic interventions addressing cognitive dysfunction in patients with AD.
Topics: Alzheimer Disease; Bayes Theorem; Cognition; Cognitive Dysfunction; Humans; Mental Status and Dementia Tests; Network Meta-Analysis; Nootropic Agents; Randomized Controlled Trials as Topic
PubMed: 31277107
DOI: 10.1097/MD.0000000000016091 -
Frontiers in Aging Neuroscience 2019Vascular dementia (VD) is a common type of disease in the elderly. Numerous clinical trials have suggested that hyperbaric oxygen is an effective and safe complementary...
Vascular dementia (VD) is a common type of disease in the elderly. Numerous clinical trials have suggested that hyperbaric oxygen is an effective and safe complementary therapy for aging-related disorders. However, there is no reliable systematic evidence regarding hyperbaric oxygen therapy (HBOT) for the treatment of VD. Therefore, we performed a meta-analysis to evaluate the clinical efficacy and safety of HBOT in treating VD. We methodically retrieved the clinical studies from eight databases (PubMed, Cochrane Library, Embase, Web of Science, Sino-Med, China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and WanFang) from their inception to November 2018. RevMan 5.3.5 was used for quality assessment and data analysis. Stata 15.1 was employed for publication bias detection and sensitivity analysis. Twenty-five randomized clinical trials (RCTs) involving 1,954 patients met our inclusion criteria. These articles researched the HBOT + oxiracetam + conventional therapy (CT) vs. oxiracetam + CT ( = 13), HBOT + butylphthalide +CT vs. butylphthalide + CT ( = 5), HBOT + donepezil + CT vs. donepezil + CT ( = 4), HBOT + nicergoline + CT vs. nicergoline + CT ( = 2) and HBOT + CT vs. CT ( = 1). The results indicated that additional HBOT strikingly improved the Mini-Mental State Examination (MMSE) ( = 4.00; 95% = 3.28-4.73; < 0.00001), activities of daily living (ADL) ( = -5.91; 95% = -6.45, -5.36; < 0.00001) and ADL by Barthel index (BADL) ( = 13.86; 95% = 5.63-22.10; = 0.001) and increased the total efficacy rate (TEF) ( = 4.84, 95% = 3.19-7.33, < 0.00001). The adverse events rates were not statistically significant between the HBOT and CT groups ( = 0.85, 95% = 0.26-2.78, = 0.79). In view of the effectiveness and safety of HBOT, the present meta-analysis suggested that HBOT can be recommended as an effective and safe complementary therapy for the treatment of VD. PROSPERO (ID: CRD42019117178). Available online at: http://www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42019117178.
PubMed: 31057392
DOI: 10.3389/fnagi.2019.00086 -
Evidence-based Complementary and... 2019The high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of... (Review)
Review
BACKGROUND
The high prevalence of delirium among postoperative patients has increased morbidity and mortality. The kind of drug that can effectively reduce the incidence of delirium has become the focus of discussion in recent years. However, a consensus in this respect has yet to be reached.
METHODS
Randomized controlled trials (RCTs) were retrieved from the PubMed, Cochrane Library, ClinicalTrials.gov, and Embase databases from their inception through October 12, 2018. We included RCTs of pharmacological prevention for postoperative delirium in adults (at least 18 years), and the Cochrane risk of bias tool was used to evaluate the methodological quality of trials. The primary outcomes were the risk ratios (RRs) of incidence of postoperative delirium, and the secondary outcomes were the RRs of mortality and adverse events in the intervention and control groups.
RESULTS
Thirty-eight trials, which comprised 20302 patients and 18 different drugs, were included in the analysis. Of the 38 studies, 17 were rated as low risk with respect to methodological quality. Dexmedetomidine administration (RR 0.58, 95%CI 0.44-0.76, P<0.01) was associated with a significantly lower incidence of postoperative delirium than the control conditions. However, the findings from the studies with a low risk of bias did not show a significant difference in this beneficial effect (RR 0.64, 95%CI 0.39-1.04, P=0.07). The antipsychotic drugs olanzapine (RR 0.44, 95%CI 0.30- 0.65, P<0.01) and risperidone (RR 0.42, 95%CI 0.19-0.92, P=0.03) had promising effects, but there was a lack of sufficient evidence to obtain a definitive conclusion. The beneficial effect of other drugs, including haloperidol, methylprednisolone, dexamethasone, gabapentin, ketamine, cyproheptadine, donepezil, hypertonic saline, melatonin, nimodipine, ondansetron, pregabalin, rivastigmine, TJ-54, and tryptophan, was not proven on the basis of present evidence.
CONCLUSION
Among the pharmacological prophylactic measures for postoperative delirium, dexmedetomidine, olanzapine, and risperidone showed higher efficacy than other drugs. However, more high-quality evidence is needed to confirm these results.
PubMed: 31001357
DOI: 10.1155/2019/9607129 -
Neural Regeneration Research May 2019To assess and compare the clinical efficacy and safety of cognitive enhancers (donepezil, galantamine, rivastigmine, and memantine) on cognition, behavior, function, and...
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.
PubMed: 30688266
DOI: 10.4103/1673-5374.249228 -
Clinical Interventions in Aging 2018The increasing prevalence of Alzheimer's disease (AD) demands more effective drugs, which are still unclear. The aim of this study is to compare the effectiveness of six...
PURPOSE
The increasing prevalence of Alzheimer's disease (AD) demands more effective drugs, which are still unclear. The aim of this study is to compare the effectiveness of six drugs, such as donepezil, rivastigmine, galantamine, memantine, huperzine-A, and tacrine, in senior AD patients and identify the most effective one to improve patients' cognitive function.
METHODS
A system of search strategies was used to identify relevant studies including randomized controlled trials and clinical controlled trials evaluating the efficacy of six drugs in patients with AD. We updated relevant studies that were published before March 2018 as full-text articles. Using Bayesian network meta-analysis (NMA), we ranked cognitive ability objectively based on Mini-Mental State Examination (MMSE). Pairwise and NMAs were sequentially performed for the efficacy of drugs compared to each drug or control group through the trials included.
RESULTS
Among the 35 trials included, no obvious heterogeneity ( =0.0%, =0.583) was revealed according to the pooled data for cognition in NMA and the mean difference (MD) of memantine (MD=1.7, 95% CI: 0.73, 2.8) showed that the memantine was significantly efficacious in the treatment group in terms of MMSE. Followed by galantamine, huperzine-A, rivastigmine, tacrine, and donepezil.
CONCLUSION
As the first NMA comparing the major drugs in market for AD, our study suggests that memantine might have a more significant benefit on cognition than other five drugs available.
Topics: Alzheimer Disease; Antiparkinson Agents; Bayes Theorem; Cholinesterase Inhibitors; Cognition; Donepezil; Galantamine; Humans; Memantine; Neuroprotective Agents; Nootropic Agents; Rivastigmine
PubMed: 30425461
DOI: 10.2147/CIA.S184968 -
CNS Neuroscience & Therapeutics Feb 2019Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy...
AIMS
Success in treating patients with atypical parkinsonian syndromes, namely progressive supranuclear palsy (PSP), cortico-basal degeneration (CBD), multiple system atrophy (MSA), Parkinson's disease with dementia (PDD), and Lewy body dementia with (LBD), remains exceedingly low. The present work overviews the most influential research literature collected on MEDLINE, ISI Web of Science, Cochrane Library, and Scopus for available treatment in atypical parkinsonisms without time restriction.
DISCUSSION
Transdermal rotigotine, autologous mesenchymal stem cells, tideglusib, and coenzyme Q10 along with donepezil, rivastigmine, memantine, and the deep brain stimulation have shown some benefits in alleviating symptoms in APS. Moreover, many new clinical trials are ongoing testing microtubule stabilizer, antitau monoclonal antibody, tau acetylation inhibition, cell replacement, selective serotonin reuptake inhibitor, active immunization, inhibition of toxic α-synuclein oligomers formation, and inhibition of microglia.
CONCLUSION
A detailed knowledge of the pathological mechanism underlying the disorders is needed, and disease-modifying therapies are required to offer better therapeutic options to physician and caregivers of APS patients.
Topics: Adult; Aged; Antiparkinson Agents; Child; Humans; Parkinsonian Disorders
PubMed: 30294976
DOI: 10.1111/cns.13068