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Journal of Alzheimer's Disease : JAD Aug 2019The clinical benefit of cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) remains inconclusive. (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical benefit of cholinesterase inhibitors (ChEIs) for mild cognitive impairment (MCI) remains inconclusive.
OBJECTIVE
We performed a systematic review and meta-analysis of the efficacy/safety of ChEIs on subjects with MCI.
METHODS
We included randomized controlled trials (RCTs) of ChEIs in subjects with MCI, using cognitive function scores as a primary outcome measure.
RESULTS
Fourteen RCTs (six using donepezil, four using galantamine, and four using rivastigmine) with 5,278 subjects were included. We found no significant difference in cognitive function scores between the ChEIs and placebo groups [standardized mean difference (SMD) = -0.06, p = 0.38, I2 = 76% ]. However, in the secondary outcomes, ChEIs were associated with a lower incidence of progression to dementia compared with placebo (risk ratio = 0.76, the number needed to treat = 20). For safety outcomes, ChEIs were associated with a lower prevalence of fall than placebo. On the other hand, compared with placebo, ChEIs were associated with a higher incidence of discontinuation due to all causes, discontinuation due to adverse events, at least one adverse event, abnormal dreams, diarrhea, dizziness, headache, insomnia, loose stools, muscle cramps, nausea, vomiting, and weight loss.
CONCLUSIONS
Although ChEIs have a slight efficacy in the treatment of MCI, there are many safety issues. Therefore, ChEIs are difficult to recommend for MCI. However, the efficacy and safety of ChEIs on MCI with a biomarker-based diagnosis is unclear. Further RCTs are needed to confirm the efficacy and safety of ChEIs when used for individual neuropathological classifications of MCI.
Topics: Cholinesterase Inhibitors; Cognitive Dysfunction; Humans; Nootropic Agents; Treatment Outcome
PubMed: 31424411
DOI: 10.3233/JAD-190546 -
Journal of Neurology Oct 2019To assess the comparative efficacy and safety of both pharmacological and non-pharmacological therapies for the behavioral and psychological symptoms of dementia, using... (Comparative Study)
Comparative Study
OBJECTIVE
To assess the comparative efficacy and safety of both pharmacological and non-pharmacological therapies for the behavioral and psychological symptoms of dementia, using direct and indirect evidence from randomized data.
METHOD
A systematic review and Bayesian network meta-analysis was conducted on only randomized controlled trials (RCTs) of all the available interventions for BPSD. RCTs were selected from Pubmed, EMBASE, the Cochrane library, and CINAHL. The efficacy outcomes were Neuropsychiatric Inventory (NPI) and Cohen-Mansfield Agitation Inventory (CMAI). The outcomes of safety were total adverse events (AEs), diarrhea, dizziness, headache, falls, nausea, vomiting, and cerebrovascular diseases.
RESULT
146 RCTs comprising 44,873 patients with BPSD were included in this study. On NPI, aripiprazole (MD - 3.65, 95% credible interval (CrI) = - 6.92 to - 0.42), escitalopram (MD - 6.79, 95% CrI - 12.91 to - 0.60), donepezil (MD - 1.45, 95% CrI - 2.70 to - 0.20), galantamine (MD - 1.80, 95% CrI - 3.29 to - 0.32), memantine (MD - 2.14, 95% CrI - 3.46 to - 0.78), and risperidone (MD - 3.20, 95% CrI - 6.08 to - 0.31) were superior to placebo. On CMAI, aripiprazole (MD - 4.00, 95% CrI - 7.39 to - 0.54) and risperidone (MD - 2.58, 95% CrI - 5.20 to - 0.6) showed superiority to placebo. On the risk of total AEs, donepezil (OR 1.27, 95% CrI 1.07-1.50), galantamine (OR 1.91, 95% CrI 1.58-2.36), risperidone (OR 1.47, 95% CrI 1.13-1.97), and rivastigmine (OR 2.02, 95% CrI 1.53-2.70) owned higher risk than placebo.
CONCLUSION
Pharmacological therapies should be the first choice for BPSD. Aripiprazole, haloperidol, quetiapine, and risperidone of antipsychotics showed the significant efficacy, while memantine, galantine, and donepezil may provide the modest effectiveness. The safety of all was thought to be acceptable.
Topics: Antipsychotic Agents; Dementia; Humans; Network Meta-Analysis; Nootropic Agents
PubMed: 30666436
DOI: 10.1007/s00415-019-09200-8 -
Neurological Sciences : Official... Feb 2024Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the... (Review)
Review
OBJECTIVE
Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common type of dementia. The early diagnosis of AD is an important factor for the control of AD progression. Electroencephalography (EEG) can be used for early diagnosis of AD. Acetylcholinesterase inhibitors (AChEIs) are also used for the amelioration of AD symptoms. In this systematic review, we reviewed the effect of different AChEIs including donepezil, rivastigmine, tacrine, physostigmine, and galantamine on EEG patterns in patients with AD.
METHODS
PubMed electronic database was searched and 122 articles were found. After removal of unrelated articles, 24 articles were selected for the present study.
RESULTS
AChEIs can decrease beta, theta, and delta frequency bands in patients with AD. However, conflicting results were found for alpha band. Some studies have shown increased alpha frequency, while others have shown decreased alpha frequency following treatment with AChEIs. The only difference was the type of drug.
CONCLUSIONS
We found that studies reporting the decreased alpha frequency used donepezil and galantamine, while studies reporting the increased alpha frequency used rivastigmine and tacrine. It was suggested that future studies should focus on the effect of different AChEIs on EEG bands, especially alpha frequency in patients with AD, to compare their effects and find the reason for their different influence on EEG patterns. Also, differences between the effects of AChEIs on oligodendrocyte differentiation and myelination may be another important factor. This is the first article investigating the effect of different AChEIs on EEG patterns in patients with AD.
Topics: Humans; Cholinesterase Inhibitors; Alzheimer Disease; Donepezil; Rivastigmine; Galantamine; Acetylcholinesterase; Tacrine; Piperidines; Indans; Phenylcarbamates
PubMed: 37843690
DOI: 10.1007/s10072-023-07114-y -
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 -
Drugs & Aging Jul 2020Deprescribing is of particular importance in older adults with limited life expectancy since this population group is highly susceptible to the potential harms of...
BACKGROUND
Deprescribing is of particular importance in older adults with limited life expectancy since this population group is highly susceptible to the potential harms of inappropriate medications.
OBJECTIVE
This systematic review aimed to explore attitudes towards deprescribing among older adults with limited life expectancy and their relatives.
METHODS
A systematic literature review was conducted in the MEDLINE and EMBASE databases from inception to October 2019. Inclusion criteria were studies specifically describing attitudes towards deprescribing among older adults (≥ 65 years) with limited life expectancy and/or their relatives regardless of study type. Results were analyzed, inspired by the Joanna Briggs Institute's method for synthesis of qualitative data.
RESULTS
A total of 842 studies were identified and screened; 84 were full-text assessed for eligibility and 7 were ultimately included. Two studies investigated the attitudes of older adults with limited life expectancy and their relatives towards deprescribing of statins and donepezil, respectively, while the five remaining studies related to attitudes towards deprescribing in general. Four main themes were identified: (1) the well-being of older adults with limited life expectancy; (2) involvement of older adults and their relatives in deprescribing; (3) the role of health care professionals in deprescribing; and (4) medication-related factors affecting deprescribing. Within each of these themes, several subthemes were identified.
CONCLUSIONS
Attitudes towards deprescribing among older adults with limited life expectancy and their relatives vary and highlight several barriers and enablers to the deprescribing process. Several of these factors must be addressed to successfully implement deprescribing initiatives in this patient group.
Topics: Aged; Deprescriptions; Donepezil; Family; Health Knowledge, Attitudes, Practice; Health Personnel; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Life Expectancy; Professional Role
PubMed: 32537682
DOI: 10.1007/s40266-020-00774-x -
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 -
Molecules (Basel, Switzerland) May 2022Down Syndrome (DS) is considered the most frequent form of Intellectual Disability, with important expressions of cognitive decline and early dementia. Studies on... (Review)
Review
Down Syndrome (DS) is considered the most frequent form of Intellectual Disability, with important expressions of cognitive decline and early dementia. Studies on potential treatments for dementia in this population are still scarce. Thus, the current review aims to synthesize the different pharmacological approaches that already exist in the literature, which focus on improving the set of symptoms related to dementia in people with DS. A total of six studies were included, evaluating the application of supplemental antioxidant therapies, such as alpha-tocopherol; the use of acetylcholinesterase inhibitor drugs, such as donepezil; N-methyl-d-aspartate (NMDA) receptor antagonists, such as memantine; and the use of vitamin E and a fast-acting intranasal insulin. Two studies observed important positive changes related to some general functions in people with DS (referring to donepezil). In the majority of studies, the use of pharmacological therapies did not lead to improvement in the set of symptoms related to dementia, such as memory and general functionality, in the population with DS.
Topics: Acetylcholinesterase; Cholinesterase Inhibitors; Dementia; Donepezil; Down Syndrome; Humans; Memantine; Randomized Controlled Trials as Topic; Receptors, N-Methyl-D-Aspartate
PubMed: 35630721
DOI: 10.3390/molecules27103244 -
JAMA Feb 2020Early identification of cognitive impairment may improve patient and caregiver health outcomes.
IMPORTANCE
Early identification of cognitive impairment may improve patient and caregiver health outcomes.
OBJECTIVE
To systematically review the test accuracy of cognitive screening instruments and benefits and harms of interventions to treat cognitive impairment in older adults (≥65 years) to inform the US Preventive Services Task Force.
DATA SOURCES
MEDLINE, PubMed, PsycINFO, and Cochrane Central Register of Controlled Trials through January 2019, with literature surveillance through November 22, 2019.
STUDY SELECTION
Fair- to good-quality English-language studies of cognitive impairment screening instruments, and pharmacologic and nonpharmacologic treatments aimed at persons with mild cognitive impairment (MCI), mild to moderate dementia, or their caregivers.
DATA EXTRACTION AND SYNTHESIS
Independent critical appraisal and data abstraction; random-effects meta-analyses and qualitative synthesis.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity; patient, caregiver, and clinician decision-making; patient function, quality of life, and neuropsychiatric symptoms; caregiver burden and well-being.
RESULTS
The review included 287 studies with more than 280 000 older adults. One randomized clinical trial (RCT) (n = 4005) examined the direct effect of screening for cognitive impairment on patient outcomes, including potential harms, finding no significant differences in health-related quality of life at 12 months (effect size, 0.009 [95% CI, -0.063 to 0.080]). Fifty-nine studies (n = 38 531) addressed the accuracy of 49 screening instruments to detect cognitive impairment. The Mini-Mental State Examination was the most-studied instrument, with a pooled sensitivity of 0.89 (95% CI, 0.85 to 0.92) and specificity of 0.89 (95% CI, 0.85 to 0.93) to detect dementia using a cutoff of 23 or less or 24 or less (15 studies, n = 12 796). Two hundred twenty-four RCTs and 3 observational studies including more than 240 000 patients or caregivers addressed the treatment of MCI or mild to moderate dementia. None of the treatment trials were linked with a screening program; in all cases, participants were persons with known cognitive impairment. Medications approved to treat Alzheimer disease (donepezil, galantamine, rivastigmine, and memantine) improved scores on the ADAS-Cog 11 by 1 to 2.5 points over 3 months to 3 years. Psychoeducation interventions for caregivers resulted in a small benefit for caregiver burden (standardized mean difference, -0.24 [95% CI, -0.36 to -0.13) over 3 to 12 months. Intervention benefits were small and of uncertain clinical importance.
CONCLUSIONS AND RELEVANCE
Screening instruments can adequately detect cognitive impairment. There is no empirical evidence, however, that screening for cognitive impairment improves patient or caregiver outcomes or causes harm. It remains unclear whether interventions for patients or caregivers provide clinically important benefits for older adults with earlier detected cognitive impairment or their caregivers.
Topics: Aged; Caregivers; Cognitive Dysfunction; Dementia; Early Diagnosis; Humans; Independent Living; Mass Screening; Neuropsychological Tests; Practice Guidelines as Topic; Sensitivity and Specificity
PubMed: 32096857
DOI: 10.1001/jama.2019.22258 -
Journal of Ethnopharmacology Jun 2023Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound... (Meta-Analysis)
Meta-Analysis
Clinical efficacy and safety of compound Congrong Yizhi Capsules on Alzheimer's disease in mainland China: A systematic review with trial sequential analysis and GRADE assessment.
ETHNOPHARMACOLOGICAL RELEVANCE
Alzheimer's disease (AD) is a degenerative disease of the central nervous system (CNS) with insidious onset. AD is also the most common cause of dementia. Compound Congrong Yizhi Capsules (CCYC), a traditional Chinese medicine compound developed by the team of Beijing University of Chinese Medicine, has been widely used to treat AD.
AIM OF THIS STUDY
To systematically evaluate the clinical efficacy and safety of CCYC for AD by meta-analysis, Trial Sequential Analysis (TSA) and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.
METHODS
This study was registered at PROSPERO (CRD42022295496). Randomized controlled trials (RCTs) of CCYC as the treatment for AD published before December 1, 2021 were retrieved from 4 Chinses databases, 4 English databases and 2 clinical trials registration systems. RevMan 5.4 and STATA 17.0 was used to conduct the meta-analysis of the included studies, the quality of outcomes was rated by the GRADE system, the TSA was conducted by TSA 0.9.5.10 software.
RESULTS
Seven studies were included, and the total sample size was 746. Meta-analysis showed that 6 months of treatment with CCYC plus conventional western medicine treatments (CTs) improved MMSE scores compared with CTs alone (WMD: 4.32, 95% CI: 3.23, 5.42), and TSA confirmed that more trials in the future will not reverse the result. Among which, CCYC combined with donepezil can significantly improve MMSE scores (WMD: 3.54, 95% CI: 2.86, 4.22). CCYC combined with olanzapine also showed good effect on both MMSE (WMD: 6.49, 95% CI: 5.54, 7.44) and ADL scores (WMD: 5.23, 95% CI: 4.63, 5.83). No serious adverse events were reported. The strengths of the evidences above are MODERATE.
CONCLUSION
CCYC combined with cognition-modifying western medicine can improve cognitive function, mental behavioural symptoms, and activities of daily living in AD patients with good safety.
Topics: Humans; Alzheimer Disease; GRADE Approach; Plant Extracts; Treatment Outcome
PubMed: 36731808
DOI: 10.1016/j.jep.2023.116208 -
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