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The Cochrane Database of Systematic... Oct 2015Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Factors contributing to subjective fatigue in people with idiopathic Parkinson's disease (PD) are not well known. This makes it difficult to manage fatigue effectively in PD.
OBJECTIVES
To evaluate the effects of pharmacological and non-pharmacological interventions, compared to an inactive control intervention, on subjective fatigue in people with PD.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library); MEDLINE (via PubMed); Ovid EMBASE; EBSCO CINAHL; Ovid PsycINFO; PEDro; and the WHO International Clinical Trials Registry Platform Search Portal up to April 2015. References of included studies and identified review articles were screened for additional studies. There were no restrictions based on language, date of publication or study setting.
SELECTION CRITERIA
Randomised controlled trials (RCTs) that report on subjective fatigue in people with PD.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed study selection, data collection and risk of bias assessments.
MAIN RESULTS
Eleven studies were eligible for this systematic review, with a total of 1817 people. Three studies included only people who experienced clinically relevant fatigue (Fatigue Severity Scale score ≥ 4 out of 7 or Multidimensional Fatigue Inventory total score > 48 out of 100), whereas all other studies did not select participants on the basis of experienced fatigue. Nine studies investigated the effects of medication (i.e. levodopa-carbidopa, memantine, rasagiline, caffeine, methylphenidate, modafinil or doxepin) on subjective fatigue. All studies were placebo controlled. There was insufficient evidence to determine the effect of doxepin on the impact of fatigue on activities in daily life (ADL) or fatigue severity (one study, N = 12, standardised mean difference (SMD) = -1.50, 95% confidence interval (CI) -2.84 to -0.15; low quality evidence). We found high quality evidence that rasagiline reduced or slowed down the progression of physical aspects of fatigue (one study, N = 1176, SMD = -0.27, 95% CI -0.39 to -0.16, I(2) = 0%). None of the other pharmacological interventions affected subjective fatigue in PD. With regard to adverse effects, only levodopa-carbidopa showed an increase for the risk of nausea (one study, N = 361, risk ratio (RR) = 1.85, 95% CI 1.05 to 3.27; high quality evidence). Two studies investigated the effect of exercise on fatigue compared with usual care. We found low quality evidence for the effect of exercise on reducing the impact of fatigue on ADL or fatigue severity (two studies, N = 57, SMD = -0.45, 95% CI -1.21 to 0.32, I(2) = 44%).
AUTHORS' CONCLUSIONS
Based on the current evidence, no clear recommendations for the treatment of subjective fatigue in PD can be provided. Doxepin may reduce the impact of fatigue on ADL and fatigue severity; however, this finding has to be confirmed in high quality studies. Rasagiline may be effective in reducing levels of physical fatigue in PD. No evidence was found for the effectiveness of levodopa-carbidopa, memantine, caffeine, methylphenidate, modafinil or exercise. Studies are needed to investigate the effect of exercise intensity on exercise capacity and subjective fatigue. Future studies should focus on interventions that address the maladaptive behavioural or cognitive aspects of fatigue in people with PD. Characteristics, such as severity and nature of perceived fatigue and underlying mood disorders should be considered to identify responders and non-responders when studying interventions for fatigue. The development of a core-set of self-report fatigue questionnaires with established responsiveness and known minimal important difference values will facilitate the interpretation of change in fatigue scores.
Topics: Central Nervous System Stimulants; Dopamine Agents; Exercise; Fatigue; Humans; Parkinson Disease; Randomized Controlled Trials as Topic
PubMed: 26447539
DOI: 10.1002/14651858.CD010925.pub2 -
The International Journal of... Aug 2018We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics for schizophrenia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
We conducted a systematic review and meta-analysis of double-blind, randomized, placebo-controlled trials of anti-dementia drugs plus antipsychotics for schizophrenia.
METHODS
Primary outcomes of efficacy and safety included improving overall symptoms (Positive and Negative Syndrome Scale and Brief Psychiatric Rating Scale scores) and all-cause discontinuation, respectively. Other outcomes included psychopathology subscales (positive, negative, general, and anxiety/depressive symptoms), cognitive function (attention/vigilance, reasoning/problem solving, social cognition, speed of processing, verbal learning, visual learning, working memory, and cognitive control/executive function), Mini-Mental State Examination scores, treatment discontinuation due to adverse events and inefficacy, and individual adverse events. We evaluated the effect size using a random effects model.
RESULTS
We identified 37 studies (n=1574): 14 donepezil-based (n=568), 10 galantamine-based (n=371), 4 rivastigmine-based (n=146), and 9 memantine-based (n=489) studies. Pooled anti-dementia drugs plus antipsychotics treatments were superior to placebo plus antipsychotics in improving the overall symptoms (24 studies, 1069 patients: standardized mean difference=-0.34, 95% CI=-0.61 to -0.08, P=.01), negative symptoms (24 studies, 1077 patients: standardized mean difference =-0.62, 95% CI=-0.92 to -0.32, Pcorrected=.00018), and Mini-Mental State Examination scores (7 studies, 225 patients: standardized mean difference=-0.79, 95% CI=-1.23 to -0.34, P=.0006). No significant differences were found between anti-dementia drugs plus antipsychotics and placebo plus antipsychotics regarding other outcomes.
CONCLUSIONS
Although the results suggest that anti-dementia drugs plus antipsychotics treatment improves negative symptoms and Mini-Mental State Examination scores in schizophrenia patients, they possibly were influenced by a small-study effect and some bias. However, it was not superior to placebo plus antipsychotics in improving composite cognitive test score, which more systematically evaluates cognitive impairment than the Mini-Mental State Examination score. Overall, the anti-dementia drugs plus antipsychotics treatment was well tolerated.
Topics: Cognition; Cognitive Dysfunction; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Schizophrenia; Schizophrenic Psychology; Treatment Outcome
PubMed: 29762677
DOI: 10.1093/ijnp/pyy045 -
The Cochrane Database of Systematic... Oct 2015People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer's disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear.
OBJECTIVES
To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome.
SEARCH METHODS
In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies.
SELECTION CRITERIA
Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary.
MAIN RESULTS
Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures.
AUTHORS' CONCLUSIONS
Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.
Topics: Acetylcarnitine; Adult; Antioxidants; Cognition; Cognition Disorders; Donepezil; Down Syndrome; Humans; Indans; Memantine; Middle Aged; Nootropic Agents; Piperidines; Randomized Controlled Trials as Topic; Simvastatin
PubMed: 26513128
DOI: 10.1002/14651858.CD011546.pub2 -
Frontiers in Neurology 2021Mild cognitive impairment (MCI) is an important stage between the normal cognitive decline of aging and dementia. The aim of this study was to compare and harmonize the...
Mild cognitive impairment (MCI) is an important stage between the normal cognitive decline of aging and dementia. The aim of this study was to compare and harmonize the recommendations for the diagnosis and treatment of MCI based on current clinical practice guidelines. We searched the PubMed, EMBASE, China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biological Medicine Database from their inception date to April 24, 2021 to identify all published guidelines on MCI. The qualities of the eligible guidelines were appraised by two reviewers using the Appraisal of Guidelines for Research and Evaluation II instrument. Thirteen guidance documents (four guidelines and nine consensus statements) with specific recommendations were included. Nine guidelines and consensus statements covered the screening and diagnosis of MCI. The evaluation of the documents showed that neuropsychological testing and biomarker assessments were the most common recommendations for the diagnosis of MCI. Nine of the 13 guidance documents covered the treatment and management of MCI. The recommendations for the treatment and management were classified into four categories, namely: intervention for risk reduction, pharmacologic interventions, non-pharmacologic interventions, and counseling. Regarding pharmacological interventions, three guidelines recommend no pharmacologic intervention. The use of cholinesterase inhibitors for MCI is contraindicated in three guidance documents, whereas one proposes that cholinesterase inhibitors and memantine should be deprescribed. EHb761, Chinese herbal decoctions, and Chinese traditional patent medicine are recommended in two documents. A total of seven guidance documents recommend non-pharmacological interventions, including physical activity interventions, cognitive interventions, dietary and nutritional interventions, and acupuncture. An updated search for possible evidence on the diagnosis and treatment of MCI is needed. Potentially effective diagnoses and treatments, either conventional or complementary, and alternative therapies should be highly valued and addressed in correlation with the supporting evidence.
PubMed: 34712197
DOI: 10.3389/fneur.2021.719849 -
Cureus Nov 2022To evaluate the role of vitamin D supplementation in preventing cognitive decline in patients with Alzheimer's disease (AD), five databases such as PubMed, PubMed... (Review)
Review
To evaluate the role of vitamin D supplementation in preventing cognitive decline in patients with Alzheimer's disease (AD), five databases such as PubMed, PubMed Central (PMC), Medical Literature Analysis and Retrieval System Online (MEDLINE), ScienceDirect, and Google Scholar were searched for articles relevant to the research question with filters such as English and human studies from 2011 to 2022. Two investigators extracted the data and assessed the quality of the study using the predefined criteria. We identified 24 relevant articles after the critical screening. There were five randomized controlled trials (RCTs), two observational studies, two systematic reviews and meta-analyses, one pilot study, and 14 review articles. Most RCTs showed no significant improvement in vitamin D supplementation except for one study, which reported significant improvement in cognition on taking vitamin D in Alzheimer's disease but was not taken much into consideration as it had a small sample size (n=210) and was for a shorter duration. Another study evidenced significant improvement in Mini-Mental State Examination (MMSE) score when memantine and vitamin D were taken together compared to when memantine and vitamin D were taken independently. Studies have shown that vitamin D deficiency is associated with an increased risk of developing cognitive impairment. But there is no sufficient evidence indicating vitamin D supplementation can improve cognitive function in Alzheimer's disease.
PubMed: 36569670
DOI: 10.7759/cureus.31710 -
Journal of Alzheimer's Disease : JAD 2023Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD)...
BACKGROUND
Alzheimer's disease (AD) is the most common type of dementia, causing progressive decline of memory, thinking, and behavior, impairing daily functioning. Early AD (eAD) includes mild cognitive impairment (MCI) due to AD and mild AD dementia.
OBJECTIVE
The aim of this study was to investigate symptomatic treatment prevalence and treatment patterns in eAD.
METHODS
Embase, MEDLINE, and EBM Reviews were searched in November 2021 for observational studies reporting symptomatic treatment patterns in eAD. The range of patients receiving treatment was collated. Risk of bias was assessed using the Joanna Briggs Institute (JBI) prevalence tool. Two independent reviewers screened the records, one performed data extraction and quality assessment while a second checked.
RESULTS
Twenty-one studies (prospective and retrospective cohorts, cross-sectional studies, and a survey) were included. Population size ranged from 23 to 2,028. Worldwide, 18 to 35% of patients diagnosed with MCI due to AD received any AChE inhibitor (three studies; n = 631), 7 to 8% memantine (two studies; n = 229), and 9% combination therapy (one study; n = 402). Patients receiving no treatment ranged from 41 to 54% (two studies; n = 733). Worldwide, in mild AD dementia patients, 13 to 89% received any AChE inhibitor (six studies; n = 3,715), 1 to 21% memantine (five studies, n = 3,527), and 0.4 to 39% combination therapy (four studies, n = 3,018). Patients receiving no treatment ranged from 9 to 26% (five studies, n = 4,073).
CONCLUSION
Limitations in reporting led to unclear risk of bias. The results reveal a pattern of use of symptomatic treatment in eAD beyond approved labels and highlights the opportunity for new consensus guidelines to inform clinical practice.
Topics: Humans; Alzheimer Disease; Memantine; Prospective Studies; Cross-Sectional Studies; Retrospective Studies; Dementia; Cognitive Dysfunction; Disease Progression
PubMed: 36404542
DOI: 10.3233/JAD-220471 -
The Cochrane Database of Systematic... 2003Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear.
OBJECTIVES
To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias.
SEARCH STRATEGY
The Cochrane Dementia & Cognitive Improvement Group's Specialized Register was searched using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian).
SELECTION CRITERIA
All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded.
DATA COLLECTION AND ANALYSIS
Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1).
MAIN RESULTS
All identified studies were performed before the 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30mg/day and 60 mg/day compared with placebo, but the number of patients treated for 6 months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials.
REVIEWER'S CONCLUSIONS
Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.
Topics: Alzheimer Disease; Cognition Disorders; Dementia; Dementia, Vascular; Humans; Nootropic Agents; Randomized Controlled Trials as Topic; Vinca Alkaloids
PubMed: 12535455
DOI: 10.1002/14651858.CD003119 -
The Cochrane Database of Systematic... Oct 2021Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate... (Review)
Review
BACKGROUND
Glutamergic system dysfunction has been implicated in the pathophysiology of bipolar depression. This is an update of the 2015 Cochrane Review for the use of glutamate receptor modulators for depression in bipolar disorder.
OBJECTIVES
1. To assess the effects of ketamine and other glutamate receptor modulators in alleviating the acute symptoms of depression in people with bipolar disorder. 2. To review the acceptability of ketamine and other glutamate receptor modulators in people with bipolar disorder who are experiencing depressive symptoms.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase and PsycINFO all years to July 2020. We did not apply any restrictions to date, language or publication status.
SELECTION CRITERIA
RCTs comparing ketamine or other glutamate receptor modulators with other active psychotropic drugs or saline placebo in adults with bipolar depression.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, assessed trial quality and extracted data. Primary outcomes were response rate and adverse events. Secondary outcomes included remission rate, depression severity change scores, suicidality, cognition, quality of life, and dropout rate. The GRADE framework was used to assess the certainty of the evidence.
MAIN RESULTS
Ten studies (647 participants) were included in this review (an additional five studies compared to the 2015 review). There were no additional studies added to the comparisons identified in the 2015 Cochrane review on ketamine, memantine and cytidine versus placebo. However, three new comparisons were found: ketamine versus midazolam, N-acetylcysteine versus placebo, and riluzole versus placebo. The glutamate receptor modulators studied were ketamine (three trials), memantine (two), cytidine (one), N-acetylcysteine (three), and riluzole (one). Eight of these studies were placebo-controlled and two-armed. In seven trials the glutamate receptor modulators had been used as add-on drugs to mood stabilisers. Only one trial compared ketamine with an active comparator, midazolam. The treatment period ranged from a single intravenous administration (all ketamine studies), to repeated administration for riluzole, memantine, cytidine, and N-acetylcysteine (with a follow-up of eight weeks, 8 to 12 weeks, 12 weeks, and 16 to 20 weeks, respectively). Six of the studies included sites in the USA, one in Taiwan, one in Denmark, one in Australia, and in one study the location was unclear. All participants had a primary diagnosis of bipolar disorder and were experiencing an acute bipolar depressive episode, diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders fourth edition (IV) or fourth edition text revision (IV-TR). Among all glutamate receptor modulators included in this review, only ketamine appeared to be more efficacious than placebo 24 hours after infusion for response rate (odds ratio (OR) 11.61, 95% confidence interval (CI) 1.25 to 107.74; P = 0.03; participants = 33; studies = 2; I² = 0%, low-certainty evidence). Ketamine seemed to be more effective in reducing depression rating scale scores (MD -11.81, 95% CI -20.01 to -3.61; P = 0.005; participants = 32; studies = 2; I = 0%, very low-certainty evidence). There was no evidence of ketamine's efficacy in producing remission over placebo at 24 hours (OR 5.16, 95% CI 0.51 to 52.30; P = 0.72; participants = 33; studies = 2; I = 0%, very low-certainty evidence). Evidence on response, remission or depression rating scale scores between ketamine and midazolam was uncertain at 24 hours due to very low-certainty evidence (OR 3.20, 95% CI 0.23 to 45.19). In the one trial assessing ketamine and midazolam, there were no dropouts due to adverse effects or for any reason (very low-certainty evidence). Placebo may have been more effective than N-acetylcysteine in reducing depression rating scale scores at three months, although this was based on very low-certainty evidence (MD 1.28, 95% CI 0.24 to 2.31; participants = 58; studies = 2). Very uncertain evidence found no difference in response at three months (OR 0.82, 95% CI 0.32 to 2.14; participants = 69; studies = 2; very low-certainty evidence). No data were available for remission or acceptability. Extremely limited data were available for riluzole vs placebo, finding only very-low certainty evidence of no difference in dropout rates (OR 2.00, 95% CI 0.31 to 12.84; P = 0.46; participants = 19; studies = 1; I = 0%).
AUTHORS' CONCLUSIONS
It is difficult to draw reliable conclusions from this review due to the certainty of the evidence being low to very low, and the relatively small amount of data usable for analysis in bipolar disorder, which is considerably less than the information available for unipolar depression. Nevertheless, we found uncertain evidence in favour of a single intravenous dose of ketamine (as add-on therapy to mood stabilisers) over placebo in terms of response rate up to 24 hours, however ketamine did not show any better efficacy for remission in bipolar depression. Even though ketamine has the potential to have a rapid and transient antidepressant effect, the efficacy of a single intravenous dose may be limited. We did not find conclusive evidence on adverse events with ketamine, and there was insufficient evidence to draw meaningful conclusions for the remaining glutamate receptor modulators. However, ketamine's psychotomimetic effects (such as delusions or delirium) may have compromised study blinding in some studies, and so we cannot rule out the potential bias introduced by inadequate blinding procedures. To draw more robust conclusions, further methodologically sound RCTs (with adequate blinding) are needed to explore different modes of administration of ketamine, and to study different methods of sustaining antidepressant response, such as repeated administrations.
Topics: Adult; Bipolar Disorder; Depression; Humans; Ketamine; Quality of Life; Receptors, Glutamate
PubMed: 34623633
DOI: 10.1002/14651858.CD011611.pub3 -
Swiss Medical Weekly Jun 2019The clinical efficacy and safety of combination therapy with acetylcholinesterase inhibitor (AChEI) and memantine compared to AChEI or memantine alone in patients with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The clinical efficacy and safety of combination therapy with acetylcholinesterase inhibitor (AChEI) and memantine compared to AChEI or memantine alone in patients with Alzheimer’s disease is inconclusive.
AIMS OF THE STUDY
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) comparing the clinical efficacy and safety of combination therapy of AChEI and memantine to monotherapy with either substance in patients with moderate to severe Alzheimer's disease (Mini-Mental State Examination score is <20).
METHODS
We systematically searched EMBASE, Medline and CENTRAL until February 2018 for eligible RCTs. We pooled the outcome data using inverse variance weighting models assuming random effects, and assessed the quality of evidence (QoE) according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE).
RESULTS
We included nine RCTs (2604 patients). At short-term follow-up (closest to 6 months), combination therapy compared to AChEI monotherapy had a significantly greater effect on cognition than AChEI monotherapy (standardised mean difference [SMD] 0.20, 95% confidence interval [CI] 0.05 to 0.35, 7 RCTs, low QoE) and clinical global impression (SMD −0.15, 95% CI −0.28 to −0.01, 4 RCTs, moderate QoE), but not on activities of daily living (SMD 0.09, 95% CI −0.01 to 0.18, 5 RCTs, moderate QoE) or behavioural and psychological symptoms of dementia (mean difference −3.07, 95% CI −6.53 to 0.38, 6 RCT, low QoE). There was no significant difference in adverse events (relative risk ratio 1.05, 95% CI 0.98 to 1.12, 4 RCTs, low QoE). Evidence for long-term follow-up (≥ 9 months) or nursing home placement was sparse. Only two studies compared combination therapy with memantine monotherapy.
CONCLUSIONS
Combination therapy had statistically significant effects on cognition and clinical global impression. The clinical relevance of these effects is uncertain. The overall QoE was very low. With the current evidence, it remains unclear whether combination therapy adds any benefit. Large pragmatic RCTs with long-term follow-up and focus on functional outcomes, delay in nursing home placement and adverse events are needed.  .
Topics: Activities of Daily Living; Alzheimer Disease; Antiparkinson Agents; Cholinesterase Inhibitors; Cognition; Drug Therapy, Combination; Humans; Memantine; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 31269225
DOI: 10.4414/smw.2019.20093 -
Annals of Internal Medicine Nov 2013Earlier identification of cognitive impairment may reduce patient and caregiver morbidity. (Review)
Review
BACKGROUND
Earlier identification of cognitive impairment may reduce patient and caregiver morbidity.
PURPOSE
To systematically review the diagnostic accuracy of brief cognitive screening instruments and the benefits and harms of pharmacologic and nonpharmacologic interventions for early cognitive impairment.
DATA SOURCES
MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials through December 2012; systematic reviews; clinical trial registries; and experts.
STUDY SELECTION
English-language studies of fair to good quality, primary care–feasible screening instruments, and treatments aimed at persons with mild cognitive impairment or mild to moderate dementia.
DATA EXTRACTION
Dual quality assessment and abstraction of relevant study details.
DATA SYNTHESIS
The Mini-Mental State Examination (k = 25) is the most thoroughly studied instrument but is not available for use without cost. Publicly available instruments with adequate test performance to detect dementia include the Clock Drawing Test (k = 7), Mini-Cog (k = 4), Memory Impairment Screen (k = 5), Abbreviated Mental Test (k = 4), Short Portable Mental Status Questionnaire (k = 4), Free and Cued Selective Reminding Test (k = 2), 7-Minute Screen (k = 2), and Informant Questionnaire on Cognitive Decline in the Elderly (k = 5). Medications approved by the U.S. Food and Drug Administration for Alzheimer disease (k = 58) and caregiver interventions (k = 59) show a small benefit of uncertain clinical importance for patients and their caregivers. Small benefits are also limited by common adverse effects of acetylcholinesterase inhibitors and limited availability of complex caregiver interventions. Although promising, cognitive stimulation (k = 6) and exercise (k = 10) have limited evidence to support their use in persons with mild to moderate dementia or mild cognitive impairment.
LIMITATION
Limited studies in persons with dementia other than Alzheimer disease and sparse reporting of important health outcomes.
CONCLUSION
Brief instruments to screen for cognitive impairment can adequately detect dementia, but there is no empirical evidence that screening improves decision making. Whether interventions for patients or their caregivers have a clinically significant effect in persons with earlier detected cognitive impairment is still unclear.
PRIMARY FUNDING SOURCE
Agency for Healthcare Research and Quality.
Topics: Aged; Caregivers; Cholinesterase Inhibitors; Decision Making; Dementia; Dopamine Agents; Early Diagnosis; Humans; Mass Screening; Memantine; Psychological Tests; Risk Assessment
PubMed: 24145578
DOI: 10.7326/0003-4819-159-9-201311050-00730