-
Journal of Sleep Research Aug 2021Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD... (Review)
Review
Suboptimal sleep causes cognitive decline and probably accelerates Alzheimer's Disease (AD) progression. Several sleep interventions have been tested in established AD dementia cases. However early intervention is needed in the course of AD at Mild Cognitive Impairment (MCI) or mild dementia stages to help prevent decline and maintain good quality of life. This systematic review aims to summarize evidence on sleep interventions in MCI and mild AD dementia. Seven databases were systematically searched for interventional studies where ≥ 75% of participants met diagnostic criteria for MCI/mild AD dementia, with a control group and validated sleep outcome measures. Studies with a majority of participants diagnosed with Moderate to Severe AD were excluded. After removal of duplicates, 22,133 references were returned in two separate searches (August 2019 and September 2020). 325 full papers were reviewed with 18 retained. Included papers reported 16 separate studies, total sample (n = 1,056), mean age 73.5 years. 13 interventions were represented: Cognitive Behavioural Therapy - Insomnia (CBT-I), A Multi-Component Group Based Therapy, A Structured Limbs Exercise Programme, Aromatherapy, Phase Locked Loop Acoustic Stimulation, Transcranial Stimulation, Suvorexant, Melatonin, Donepezil, Galantamine, Rivastigmine, Tetrahydroaminoacridine and Continuous Positive Airway Pressure (CPAP). Psychotherapeutic approaches utilising adapted CBT-I and a Structured Limbs Exercise Programme each achieved statistically significant improvements in the Pittsburgh Sleep Quality Index with one study reporting co-existent improved actigraphy variables. Suvorexant significantly increased Total Sleep Time and Sleep Efficiency whilst reducing Wake After Sleep Onset time. Transcranial Stimulation enhanced cortical slow oscillations and spindle power during daytime naps. Melatonin significantly reduced sleep latency in two small studies and sleep to wakefulness transitions in a small sample. CPAP demonstrated efficacy in participants with Obstructive Sleep Apnoea. Evidence to support other interventions was limited. Whilst new evidence is emerging, there remains a paucity of evidence for sleep interventions in MCI and mild AD highlighting a pressing need for high quality experimental studies exploring alternative sleep interventions.
Topics: Alzheimer Disease; Cognitive Dysfunction; Humans; Quality of Life; Sleep
PubMed: 33289311
DOI: 10.1111/jsr.13229 -
Journal of Alzheimer's Disease : JAD 2022Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Evidence summaries for efficacy and safety of frequently employed treatments of Alzheimer's disease (AD) are sparse.
OBJECTIVE
We aimed to perform an updated umbrella review to identify an efficacious and safe treatment for AD patients.
METHODS
We conducted a search for meta-analyses and systematic reviews on the Embase, PubMed, The Cochrane Library, and Web of Science to address this knowledge gap. We examined the cognitive functions, behavioral symptoms, global clinical assessment, and Activities of Daily Living as efficacy endpoints, and the incidence of adverse events as safety profiles.
RESULTS
Sixteen eligible papers including 149 studies were included in the umbrella review. The results showed that AChE inhibitors (donepezil, galantamine, rivastigmine, Huperzine A), Ginkgo biloba, and cerebrolysin appear to be beneficial for cognitive, global performances, and activities of daily living in patients with AD. Furthermore, anti-Aβ agents are unlikely to have an important effect on slowing cognitive or functional impairment in mild to moderate AD.
CONCLUSION
Our study demonstrated that AChE inhibitors, Ginkgo biloba, and cerebrolysin are the optimum cognitive and activities of daily living medication for patients with AD.
Topics: Activities of Daily Living; Alzheimer Disease; Amino Acids; Cholinesterase Inhibitors; Cognition; Donepezil; Galantamine; Ginkgo biloba; Humans; Nootropic Agents; Patient Safety; Plant Extracts; Rivastigmine
PubMed: 34924395
DOI: 10.3233/JAD-215423 -
Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
BMJ Open Apr 2022To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD). (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To examine the comparative efficacy and safety of cognitive enhancers by patient characteristics for managing Alzheimer's dementia (AD).
DESIGN
Systematic review and individual patient data (IPD) network meta-analysis (NMA) based on our previously published systematic review and aggregate data NMA.
DATA SOURCES
MEDLINE, Embase, Cochrane Methodology Register, CINAHL, AgeLine and Cochrane Central Register of Controlled Trials up to March 2016.
PARTICIPANTS
80 randomised controlled trials (RCTs) including 21 138 adults with AD, and 12 RCTs with IPD including 6906 patients.
INTERVENTIONS
Cognitive enhancers (donepezil, rivastigmine, galantamine and memantine) alone or in any combination against other cognitive enhancers or placebo.
DATA EXTRACTION AND SYNTHESIS
We requested IPD from authors, sponsors and data sharing platforms. When IPD were not available, we used aggregate data. We appraised study quality with the Cochrane risk-of-bias. We conducted a two-stage random-effects IPD-NMA, and assessed their findings using CINeMA (Confidence in Network Meta-Analysis).
PRIMARY AND SECONDARY OUTCOMES
We included trials assessing cognition with the Mini-Mental State Examination (MMSE), and adverse events.
RESULTS
Our IPD-NMA compared nine treatments (including placebo). Donepezil (mean difference (MD)=1.41, 95% CI: 0.51 to 2.32) and donepezil +memantine (MD=2.57, 95% CI: 0.07 to 5.07) improved MMSE score (56 RCTs, 11 619 participants; CINeMA score: moderate) compared with placebo. According to P-score, oral rivastigmine (OR=1.26, 95% CI: 0.82 to 1.94, P-score=16%) and donepezil (OR=1.08, 95% CI: 0.87 to 1.35, P-score=30%) had the least favourable safety profile, but none of the estimated treatment effects were sufficiently precise when compared with placebo (45 RCTs, 15 649 patients; CINeMA score: moderate to high). For moderate-to-severe impairment, donepezil, memantine and their combination performed best, but for mild-to-moderate impairment donepezil and transdermal rivastigmine ranked best. Adjusting for MMSE baseline differences, oral rivastigmine and galantamine improved MMSE score, whereas when adjusting for comorbidities only oral rivastigmine was effective.
CONCLUSIONS
The choice among the different cognitive enhancers may depend on patient's characteristics. The MDs of all cognitive enhancer regimens except for single-agent oral rivastigmine, galantamine and memantine, against placebo were clinically important for cognition (MD larger than 1.40 MMSE points), but results were quite imprecise. However, two-thirds of the published RCTs were associated with high risk of bias for incomplete outcome data, and IPD were only available for 15% of the included RCTs.
PROSPERO REGISTRATION NUMBER
CRD42015023507.
Topics: Adult; Alzheimer Disease; Donepezil; Galantamine; Humans; Memantine; Network Meta-Analysis; Nootropic Agents; Rivastigmine
PubMed: 35473731
DOI: 10.1136/bmjopen-2021-053012 -
The Cochrane Database of Systematic... Jun 2022Most people with Parkinson's disease (PD) experience at least one fall during the course of their disease. Several interventions designed to reduce falls have been... (Review)
Review
BACKGROUND
Most people with Parkinson's disease (PD) experience at least one fall during the course of their disease. Several interventions designed to reduce falls have been studied. An up-to-date synthesis of evidence for interventions to reduce falls in people with PD will assist with informed decisions regarding fall-prevention interventions for people with PD.
OBJECTIVES
To assess the effects of interventions designed to reduce falls in people with PD.
SEARCH METHODS
CENTRAL, MEDLINE, Embase, four other databases and two trials registers were searched on 16 July 2020, together with reference checking, citation searching and contact with study authors to identify additional studies. We also conducted a top-up search on 13 October 2021.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of interventions that aimed to reduce falls in people with PD and reported the effect on falls. We excluded interventions that aimed to reduce falls due to syncope.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Review procedures. Primary outcomes were rate of falls and number of people who fell at least once. Secondary outcomes were the number of people sustaining one or more fall-related fractures, quality of life, adverse events and economic outcomes. The certainty of the evidence was assessed using GRADE.
MAIN RESULTS
This review includes 32 studies with 3370 participants randomised. We included 25 studies of exercise interventions (2700 participants), three studies of medication interventions (242 participants), one study of fall-prevention education (53 participants) and three studies of exercise plus education (375 participants). Overall, participants in the exercise trials and the exercise plus education trials had mild to moderate PD, while participants in the medication trials included those with more advanced disease. All studies had a high or unclear risk of bias in one or more items. Illustrative risks demonstrating the absolute impact of each intervention are presented in the summary of findings tables. Twelve studies compared exercise (all types) with a control intervention (an intervention not thought to reduce falls, such as usual care or sham exercise) in people with mild to moderate PD. Exercise probably reduces the rate of falls by 26% (rate ratio (RaR) 0.74, 95% confidence interval (CI) 0.63 to 0.87; 1456 participants, 12 studies; moderate-certainty evidence). Exercise probably slightly reduces the number of people experiencing one or more falls by 10% (risk ratio (RR) 0.90, 95% CI 0.80 to 1.00; 932 participants, 9 studies; moderate-certainty evidence). We are uncertain whether exercise makes little or no difference to the number of people experiencing one or more fall-related fractures (RR 0.57, 95% CI 0.28 to 1.17; 989 participants, 5 studies; very low-certainty evidence). Exercise may slightly improve health-related quality of life immediately following the intervention (standardised mean difference (SMD) -0.17, 95% CI -0.36 to 0.01; 951 participants, 5 studies; low-certainty evidence). We are uncertain whether exercise has an effect on adverse events or whether exercise is a cost-effective intervention for fall prevention. Three studies trialled a cholinesterase inhibitor (rivastigmine or donepezil). Cholinesterase inhibitors may reduce the rate of falls by 50% (RaR 0.50, 95% CI 0.44 to 0.58; 229 participants, 3 studies; low-certainty evidence). However, we are uncertain if this medication makes little or no difference to the number of people experiencing one or more falls (RR 1.01, 95% CI 0.90 to 1.14230 participants, 3 studies) and to health-related quality of life (EQ5D Thermometer mean difference (MD) 3.00, 95% CI -3.06 to 9.06; very low-certainty evidence). Cholinesterase inhibitors may increase the rate of non fall-related adverse events by 60% (RaR 1.60, 95% CI 1.28 to 2.01; 175 participants, 2 studies; low-certainty evidence). Most adverse events were mild and transient in nature. No data was available regarding the cost-effectiveness of medication for fall prevention. We are uncertain of the effect of education compared to a control intervention on the number of people who fell at least once (RR 10.89, 95% CI 1.26 to 94.03; 53 participants, 1 study; very low-certainty evidence), and no data were available for the other outcomes of interest for this comparisonWe are also uncertain (very low-certainty evidence) whether exercise combined with education makes little or no difference to the number of falls (RaR 0.46, 95% CI 0.12 to 1.85; 320 participants, 2 studies), the number of people sustaining fall-related fractures (RR 1.45, 95% CI 0.40 to 5.32,320 participants, 2 studies), or health-related quality of life (PDQ39 MD 0.05, 95% CI -3.12 to 3.23, 305 participants, 2 studies). Exercise plus education may make little or no difference to the number of people experiencing one or more falls (RR 0.89, 95% CI 0.75 to 1.07; 352 participants, 3 studies; low-certainty evidence). We are uncertain whether exercise combined with education has an effect on adverse events or is a cost-effective intervention for fall prevention. AUTHORS' CONCLUSIONS: Exercise interventions probably reduce the rate of falls, and probably slightly reduce the number of people falling in people with mild to moderate PD. Cholinesterase inhibitors may reduce the rate of falls, but we are uncertain if they have an effect on the number of people falling. The decision to use these medications needs to be balanced against the risk of non fall-related adverse events, though these adverse events were predominantly mild or transient in nature. Further research in the form of large, high-quality RCTs are required to determine the relative impact of different types of exercise and different levels of supervision on falls, and how this could be influenced by disease severity. Further work is also needed to increase the certainty of the effects of medication and further explore falls prevention education interventions both delivered alone and in combination with exercise.
Topics: Cholinesterase Inhibitors; Exercise; Fractures, Bone; Humans; Parkinson Disease; Quality of Life
PubMed: 35665915
DOI: 10.1002/14651858.CD011574.pub2 -
The Cochrane Database of Systematic... Feb 2021Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Vascular cognitive impairment (VCI) describes a broad spectrum of cognitive impairments caused by cerebrovascular disease, ranging from mild cognitive impairment to dementia. There are currently no pharmacological treatments recommended for improving either cognition or function in people with VCI. Three cholinesterase inhibitors (donepezil, galantamine, and rivastigmine) are licenced for the treatment of dementia due to Alzheimer's disease. They are thought to work by compensating for reduced cholinergic neurotransmission, which is also a feature of VCI. Through pairwise comparisons with placebo and a network meta-analysis, we sought to determine whether these medications are effective in VCI and whether there are differences between them with regard to efficacy or adverse events.
OBJECTIVES
(1) To assess the efficacy and safety of cholinesterase inhibitors in the treatment of adults with vascular dementia and other VCI. (2) To compare the effects of different cholinesterase inhibitors on cognition and adverse events, using network meta-analysis.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group's register, MEDLINE (OvidSP), Embase (OvidSP), PsycINFO (OvidSP), CINAHL (EBSCOhost), Web of Science Core Collection (ISI Web of Science), LILACS (BIREME), ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform on 19 August 2020.
SELECTION CRITERIA
We included randomised controlled trials in which donepezil, galantamine, or rivastigmine was compared with placebo or in which the drugs were compared with each other in adults with vascular dementia or other VCI (excluding cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)). We included all drug doses and routes of administration.
DATA COLLECTION AND ANALYSIS
Two review authors independently identified eligible trials, extracted data, assessed risk of bias, and applied the GRADE approach to assess the certainty of the evidence. The primary outcomes were cognition, clinical global impression, function (performance of activities of daily living), and adverse events. Secondary outcomes were serious adverse events, incidence of development of new dementia, behavioural disturbance, carer burden, institutionalisation, quality of life and death. For the pairwise analyses, we pooled outcome data at similar time points using random-effects methods. We also performed a network meta-analysis using Bayesian methods.
MAIN RESULTS
We included eight trials (4373 participants) in the review. Three trials studied donepezil 5 mg or 10 mg daily (n= 2193); three trials studied rivastigmine at a maximum daily dose of 3 to 12 mg (n= 800); and two trials studied galantamine at a maximum daily dose of 16 to 24 mg (n= 1380). The trials included participants with possible or probable vascular dementia or cognitive impairment following stroke. Mean ages were between 72.2 and 73.9 years. All of the trials were at low or unclear risk of bias in all domains, and the evidence ranged from very low to high level of certainty. For cognition, the results showed that donepezil 5 mg improves cognition slightly, although the size of the effect is unlikely to be clinically important (mean difference (MD) -0.92 Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) points (range 0 to 70), 95% confidence interval (CI) -1.44 to -0.40; high-certainty evidence). Donepezil 10 mg (MD -2.21 ADAS-Cog points, 95% CI -3.07 to -1.35; moderate-certainty evidence) and galantamine 16 to 24 mg (MD -2.01 ADAS-Cog point, 95%CI -3.18 to -0.85; moderate-certainty evidence) probably also improve cognition, although the larger effect estimates still may not be clinically important. With low certainty, there may be little to no effect of rivastigmine 3 to 12 mg daily on cognition (MD 0.03 ADAS-Cog points, 95% CI -3.04 to 3.10; low-certainty evidence). Adverse events reported in the studies included nausea and/or vomiting, diarrhoea, dizziness, headache, and hypertension. The results showed that there was probably little to no difference between donepezil 5 mg and placebo in the number of adverse events (odds ratio (OR) 1.22, 95% CI 0.94 to 1.58; moderate-certainty evidence), but there were slightly more adverse events with donepezil 10 mg than with placebo (OR 1.95, 95% CI 1.20 to 3.15; high-certainty evidence). The effect of rivastigmine 3 to 12 mg on adverse events was very uncertain (OR 3.21, 95% CI 0.36 to 28.88; very low-certainty evidence). Galantamine 16 to 24 mg is probably associated with a slight excess of adverse events over placebo (OR 1.57, 95% CI 1.02 to 2.43; moderate-certainty evidence). In the network meta-analysis (NMA), we included cognition to represent benefit, and adverse events to represent harm. All drugs ranked above placebo for cognition and below placebo for adverse events. We found donepezil 10 mg to rank first in terms of benefit, but third in terms of harms, when considering the network estimates and quality of evidence. Galantamine was ranked second in terms of both benefit and harm. Rivastigmine had the lowest ranking of the cholinesterase inhibitors in both benefit and harm NMA estimates, but this may reflect possibly inadequate doses received by some trial participants and small trial sample sizes.
AUTHORS' CONCLUSIONS
We found moderate- to high-certainty evidence that donepezil 5 mg, donepezil 10 mg, and galantamine have a slight beneficial effect on cognition in people with VCI, although the size of the change is unlikely to be clinically important. Donepezil 10 mg and galantamine 16 to 24 mg are probably associated with more adverse events than placebo. The evidence for rivastigmine was less certain. The data suggest that donepezil 10 mg has the greatest effect on cognition, but at the cost of adverse effects. The effect is modest, but in the absence of any other treatments, people living with VCI may still wish to consider the use of these agents. Further research into rivastigmine is needed, including the use of transdermal patches.
Topics: Activities of Daily Living; Bias; Cholinesterase Inhibitors; Cognition; Dementia, Vascular; Donepezil; Galantamine; Humans; Network Meta-Analysis; Nootropic Agents; Physical Functional Performance; Placebos; Randomized Controlled Trials as Topic; Rivastigmine
PubMed: 33704781
DOI: 10.1002/14651858.CD013306.pub2 -
Brain Sciences Jul 2023Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely... (Review)
Review
OBJECTIVE
Apathy, a frequent neuropsychiatric symptom in aging neurocognitive disorders, has been associated with cognitive decline and functional disability. Therefore, timely provision of pharmacological interventions for apathy is greatly needed.
DESIGN
A systematical literature review of existing studies was conducted up to 30 May 2023 in several databases (PubMed, PsychInfo, Cochrane, Google Scholar, etc.) that included randomized controlled trials (RCTs) and meta-analyses assessing pharmacological treatments for apathy in aging neurocognitive disorders. The quality of the studies was appraised.
RESULTS
In patients with Alzheimer's Disease (AD), donepezil, galantamine, rivastigmine, methylphenidate, and gingko biloba were proven efficacious for apathy, while rivastigmine, cognitive enhancer IRL752 and piribedil were found to be beneficial in patients with Parkinson's Disease (PD) and agomelatine in patients with Frontotemporal Dementia (FD). The extensive proportion of RCTs in which apathy was used as a secondary outcome measure, along with the considerable methodological heterogeneity, did not allow the evaluation of group effects.
CONCLUSIONS
Pharmacological interventions for apathy in aging neurocognitive disorders are complex and under-investigated. The continuation of systematic research efforts and the provision of individualized treatment for patients suffering from these disorders is vital.
PubMed: 37508993
DOI: 10.3390/brainsci13071061 -
Frontiers in Pharmacology 2023Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social...
Stroke survivors are at significantly increased risk of cognitive impairment, which affects patients' independence of activities of daily living (ADLs), social engagement, and neurological function deficit. Many studies have been done to evaluate the efficacy and safety of post-stroke cognitive impairment (PSCI) treatment, and due to the largely inconsistent clinical data, there is a need to summarize and analyze the published clinical research data in this area. An umbrella review was performed to evaluate the efficacy and safety of PSCI therapies. Three independent authors searched for meta-analyses and systematic reviews on PubMed, the Cochrane Library, and the Web of Science to address this issue. We examined ADL and Barthel index (BI), Montreal Cognitive Assessment (MoCA), neurological function deficit as efficacy endpoints, and the incidence of adverse events as safety profiles. In all, 312 studies from 19 eligible publications were included in the umbrella review. The results showed that angiotensin-converting enzyme inhibitors (ACEI) and N-methyl-D-aspartate (NMDA) antagonists, cell therapies, acupuncture, and EGB76 can improve the MoCA and ADL, and the adverse effects were mild for the treatment of PSCI. Moreover, Vinpocetine, Oxiracetam, Citicoline, thrombolytic therapy, Actovegin, DL-3-n-Butylphthalide, and Nimodipine showed adverse events or low article quality in patients with PSCI. However, the research evidence is not exact and further research is needed. Our study demonstrated that ACEI inhibitors (Donepezil) and NMDA antagonists (Memantine), EGB761, and acupuncture are the ADL and BI, MoCA, and neurological function deficit medication/therapy, respectively, for patients with PSCI. https://inplasy.com/inplasy-2022-11-0139/; Identifier: INPLASY2022110139.
PubMed: 37693907
DOI: 10.3389/fphar.2023.1207075 -
The Cochrane Database of Systematic... Jun 2023Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (autism) is a neurodevelopmental condition characterised by impairments in social communication and interaction, plus restricted, repetitive patterns of behaviour and interests. Whilst some people embrace autism as part of their identity, others struggle with their difficulties, and some seek treatment. There are no current interventions that result in complete reduction of autism features. Acetylcholine is a neurotransmitter for the cholinergic system and has a role in attention, novelty seeking, and memory. Low levels of acetylcholine have been investigated as a potential contributor to autism symptomatology. Donepezil, galantamine, and rivastigmine (commonly referred to as acetylcholinesterase inhibitors) all inhibit acetylcholinesterase, and have slightly different modes of action and biological availability, so their effectiveness and side-effect profiles may vary. The effect of various acetylcholinesterase inhibitor on core autism features across the lifespan, and possible adverse effects, have not been thoroughly investigated.
OBJECTIVES
To evaluate the efficacy and harms of acetylcholinesterase inhibitors for people with the core features (social interaction, communication, and restrictive and repetitive behaviours) of autism. To assess the effects of acetylcholinesterase inhibitors on non-core features of autism.
SEARCH METHODS
In November 2022, we searched CENTRAL, MEDLINE, Embase, eight other databases, and two trials registers. We also searched the reference lists of included studies and relevant reviews, and contacted authors of relevant studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs), comparing acetylcholinesterase inhibitors (e.g. galantamine, donepezil, or rivastigmine) of varying doses, delivered orally or via transdermal patch, either as monotherapy or adjunct therapy, with placebo. People of any age, with a clinical diagnosis of autism were eligible for inclusion.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by Cochrane. Our primary outcomes were core features of autism and adverse effects. Secondary outcomes were language, irritability, hyperactivity, and general health and function. We used GRADE to assess certainty of evidence.
MAIN RESULTS
We included two RCTs (74 participants). One study was conducted in Iran, the second in the USA, although exact location in the USA is unclear. Galantamine plus risperidone versus placebo plus risperidone One study compared the effects of galantamine plus risperidone to placebo plus risperidone (40 participants, aged 4 years to 12 years). Primary and secondary outcomes of interest were measured postintervention, using subscales of the Aberrant Behavior Checklist (score 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed there was little to no difference between the two groups postintervention for social communication (mean difference (MD) -2.75, 95% confidence interval (CI) -5.88 to 0.38), and restricted and repetitive behaviour (MD -0.55, 95% CI -3.47 to 2.37). Overall autism features were not assessed. Adverse events may be higher in the galantamine plus risperidone group (75%) compared with the placebo plus risperidone group (35%): odds ratio 5.57, 95% CI 1.42 to 21.86, low-certainty evidence. No serious adverse events were reported. Low-certainty evidence showed a small difference in irritability (MD -3.50, 95% CI -6.39 to -0.61), with the galantamine plus risperidone group showing a greater decline on the irritability subscale than the placebo group postintervention. There was no evidence of a difference between the groups in hyperactivity postintervention (MD -5.20, 95% CI -10.51 to 0.11). General health and function were not assessed. Donepezil versus placebo One study compared donepezil to placebo (34 participants aged 8 years to 17 years). Primary outcomes of interest were measured postintervention, using subscales of the Modified Version of The Real Life Rating Scale (scored 0 to 3; higher scores = greater impairment). Very low-certainty evidence showed no evidence of group differences immediately postintervention in overall autism features (MD 0.07, 95% CI -0.19 to 0.33), or in the autism symptom domains of social communication (MD -0.02, 95% CI -0.34 to 0.30), and restricted and repetitive behaviours (MD 0.04, 95% CI -0.27 to 0.35). Significant adverse events leading to study withdrawal in at least one participant was implied in the data analysis section, but not explicitly reported. The evidence is very uncertain about the effect of donepezil, compared to placebo, on the secondary outcomes of interest, including irritability (MD 1.08, 95% CI -0.41 to 2.57), hyperactivity (MD 2.60, 95% CI 0.50 to 4.70), and general health and function (MD 0.03, 95% CI -0.48 to 0.54) postintervention. Across all analyses within this comparison, we judged the evidence to be very low-certainty due to high risk of bias, and very serious imprecision (results based on one small study with wide confidence intervals). The study narratively reported adverse events for the study as a whole, rather than by treatment group.
AUTHORS' CONCLUSIONS
Evidence about the effectiveness of acetylcholinesterase inhibitors as a medication to improve outcomes for autistic adults is lacking, and for autistic children is very uncertain. There is a need for more evidence of improvement in outcomes of relevance to clinical care, autistic people, and their families. There are a number of ongoing studies involving acetylcholinesterase inhibitors, and future updates of this review may add to the current evidence.
Topics: Child; Humans; Acetylcholine; Autism Spectrum Disorder; Cholinesterase Inhibitors; Donepezil; Galantamine; Risperidone; Rivastigmine; Child, Preschool; Adolescent
PubMed: 37267443
DOI: 10.1002/14651858.CD013851.pub2 -
Clinical Neurology and Neurosurgery Feb 2022This study intends to systematically evaluate the efficacy and safety of donepezil for improving cognitive function in patients with mild cognitive impairment (MCI), and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study intends to systematically evaluate the efficacy and safety of donepezil for improving cognitive function in patients with mild cognitive impairment (MCI), and to provide evidence-based foundation for donepezil in MCI treatment.
METHODS
We searched in PubMed, Embase, Cochrane Library, Clinical trials.gov, Web of Science, CQVIP, and CNKI databases, and then we summarized the interventional and observational studies on the use of donepezil for improving the cognitive function of MCI patients. The literature was collected according to the inclusion criteria for data extraction. We evaluated the quality of the selected literature and used Stata 15.0 for meta-analysis.
RESULTS
A total of 12 randomized controlled trials (RCTs) and 5 non-randomized concurrent controlled trials (CCTs) were included, and a total of 2847 patients were included. In terms of efficacy, meta-analysis showed that donepezil could significantly improve the MMSE (SMD: 0.85, 95%CI: 0.40-1.31) and MoCA (SMD: 1.88, 95%CI: 0.32-3.45) scores of MCI patients. Donepezil could not significantly reduce ADAS-cog score, nor could it significantly delay disease progression. The quality of the evidence was low overall. In terms of safety, donepezil could significantly increase the risk of adverse reactions such as nausea, vomiting, diarrhea in patients with MCI.
CONCLUSION
Donepezil can improve the cognitive function of MCI patients to a certain extent. However, there is no trend of significantly delaying the progression of the disease, and it is easy to lead to the occurrence of adverse reactions.
Topics: Cognition; Cognitive Dysfunction; Databases, Factual; Donepezil; Humans; Nootropic Agents; Randomized Controlled Trials as Topic
PubMed: 35078087
DOI: 10.1016/j.clineuro.2022.107134