Effect of N-methyl-D-aspartate-receptor-enhancing agents on cognition in patients with schizophrenia: A systematic review and meta-analysis of double-blind randomised controlled trials

2019 ◽  
Vol 33 (4) ◽  
pp. 436-448 ◽  
Author(s):  
Chun-Hung Chang ◽  
Hsien-Yuan Lane ◽  
Ping-Tao Tseng ◽  
Shaw-Ji Chen ◽  
Chieh-Yu Liu ◽  
...  
Keyword(s):  
Working Memory ◽  
Cognitive Function ◽  
Nmda Receptor ◽  
Rating Scales ◽  
Meta Analysis ◽  
Random Effect Model ◽  
Double Blind ◽  
Cognitive Domains ◽  
Positive Effects ◽  
Statistical Heterogeneity

Background: Multiple N-methyl-d-aspartate (NMDA)-receptor-enhancing agents have demonstrated promising effects for cognition in schizophrenia. However, the results of studies have been conflicting. This updated meta-analysis explored the effect of NMDA-receptor-enhancing agents on cognitive function. Methods: We searched PubMed, the Cochrane Collaboration Central Register of Controlled Clinical Trials and Cochrane Systematic Reviews for studies on the effect of NMDA-receptor-enhancing agents on cognitive function in patients with schizophrenia up to September 2018. Double-blind randomised placebo trials with cognition rating scales were included. We pooled studies by using a random-effect model for comparisons with add-on NMDA-receptor-enhancing agents. Cognitive function scores were compared between baseline and subsequent levels, and NMDA-receptor-positive modulators were assessed using the standardised mean difference (SMD) with 95% confidence intervals (CIs). We evaluated statistical heterogeneity through visual inspection of funnel plots and by using the I2 statistic. Results: We identified 25 trials with 1951 participants meeting the inclusion criteria. NMDA-receptor-enhancing agents had a small but nonsignificant effect compared with the placebo on overall cognitive function (SMD = 0.068, CI = −0.056 to 0.193, P = 0.283). We identified trials enrolling patients aged between 30 and 39 years old, which reported significant positive effects (SMD: 0.163, 95% CI: 0.016–0.310, P = 0.030). Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function. Moreover, subgroup meta-analysis of cognitive domains revealed that N-acetyl cysteine (NAC) had a significant effect on working memory ( P-value for interaction = 0.038; SMD = 0.679, CI = 0.397–0.961, P < 0.001). Conclusions: Our meta-analysis revealed no significant effect of NMDA-enhancing agents on overall cognition. However, subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia, and NAC may have an effect on working memory. Additional trials with larger samples are suggested to evaluate these cognitive domains and ascertain the possible mechanisms.

scholarly journals Effect of N-methyl-d-aspartate receptor enhancing agents on cognition in dementia: an exploratory systematic review and meta-analysis of randomized controlled trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Chun-Hung Chang ◽  
Chieh-Yu Liu ◽  
Shaw-Ji Chen ◽  
Hsin-Chi Tsai
Keyword(s):  
Cognitive Function ◽  
Nmda Receptor ◽  
Randomized Controlled Trials ◽  
Meta Analysis ◽  
Disease Assessment ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Randomized Controlled ◽  
Statistical Heterogeneity ◽  
Agent Treatment

AbstractMultiple N-methyl-d-aspartate (NMDA) receptor enhancing agents have had promising effects on cognition among patients with dementia. However, the results remain inconsistent. This exploratory meta-analysis investigated the effectiveness of NMDA receptor enhancing agents for cognitive function. PubMed, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews were searched for randomized controlled trials (RCTs). Controlled trials assessing add-on NMDA receptor enhancing agent treatment in patients with dementia and using cognition rating scales were eligible and pooled using a random-effect model for comparisons. The standardized mean difference (SMD) was calculated in each study from the effect size; positive values indicated that NMDA receptor enhancing agent treatment improved cognitive function. Funnel plots and the I2 statistic were evaluated for statistical heterogeneity. Moderators were evaluated using meta-regression. We identified 14 RCTs with 2224 participants meeting the inclusion criteria. Add-on NMDA receptor enhancing agents had small positive significant effects on overall cognitive function among patients with dementia (SMD = 0.1002, 95% CI 0.0105–0.1900, P = 0.02860). Subgroup meta-analysis showed patients with Alzheimer’s Disease and trials using the Alzheimer Disease Assessment Scale-cognitive subscale as the primary outcome had small positive significant effects (SMD = 0.1042, 95% CI 0.0076–0.2007, P = 0.03451; SMD = 0.1267, 95% CI 0.0145–0.2388, P = 0.2686). This exploratory meta-analysis showed a very small, positive, and significant effect on overall cognition function in patients with dementia. Studies with larger samples are needed to evaluate different cognitive domains and phases of dementia.

scholarly journals The Effect of Curcumin Differs on Individual Cognitive Domains across Different Patient Populations: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 14 (12) ◽  
pp. 1235
Author(s):  
I-Chen Tsai ◽  
Chih-Wei Hsu ◽  
Chun-Hung Chang ◽  
Ping-Tao Tseng ◽  
Ke-Vin Chang
Keyword(s):  
Working Memory ◽  
Placebo Group ◽  
Cognitive Function ◽  
Processing Speed ◽  
Verbal Memory ◽  
Meta Analysis ◽  
Visual Learning ◽  
Clinical Effectiveness ◽  
Cognitive Domains ◽  
Significant Difference

Curcumin is a polyphenol with strong antioxidant and anti-inflammatory effects that has been shown to be effective in ameliorating cognitive decline in animal studies. However, its clinical effectiveness is inconclusive, and relevant gastrointestinal adverse events (AEs) have been reported. The aim of this meta-analysis was to summarize the existing evidence from randomized controlled trials (RCTs) of effects of curcumin on overall cognitive function, individual cognitive domains, and gastrointestinal AE. The study includes 8 RCTs and 389 participants. A random-effects model was used for the meta-analysis. Compared with the placebo group, the curcumin group was associated with an improvement in working memory (Hedges’ g = 0.396, 95% confidence interval (CI) = 0.078 to 0.714, p = 0.015) and a borderline benefit in processing speed (Hedges’ g = 0.303, 95% CI = ‒0.013 to 0.619, p = 0.06). In the domains of language, episodic memory/visual learning, verbal memory, cognitive flexibility/problem solving, and overall cognitive function, no significant difference existed for the comparison between the curcumin and placebo groups. The curcumin group had a significantly higher risk of gastrointestinal AEs than the placebo group (odds ratio = 3.019, 95% CI = 1.118 to 8.150, p = 0.029). In the future, the effects of curcumin on working memory, processing speed, and gastrointestinal AE should be further investigated.

Pharmacological Treatment of Osteoporosis in Elderly People: A Systematic Review and Meta-Analysis

Gerontology ◽  
2021 ◽  
pp. 1-11
Author(s):  
Qin-Yi Wang ◽  
Na Ding ◽  
Yi-He Dong ◽  
Zhang-Xin Wen ◽  
Rong Chen ◽  
...  
Keyword(s):  
Adverse Events ◽  
Elderly Patients ◽  
Meta Analysis ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Anabolic Agents ◽  
Double Blind ◽  
Antiresorptive Agents ◽  
Statistical Heterogeneity ◽  
Post Hoc

<b><i>Background:</i></b> The evidence supporting the use of antiresorptive and anabolic agents for fracture prevention in elderly patients is still inconclusive. Whether it is too late to alter the course of the disease in this age-group has remained uncertain. <b><i>Objectives:</i></b> The objective of this study was to determine the efficacy and safety of antiresorptive and anabolic agents in elderly patients. <b><i>Methods:</i></b> PubMed, Web of Science, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and post hoc analyses of RCTs reporting efficacy outcomes or adverse events of antiresorptive and anabolic agents in elderly patients. Statistical heterogeneity was assessed with the Cochran <i>Q</i> χ<sup>2</sup> test and <i>I</i><sup>2</sup> statistic. All results were expressed as relative risk (RR) with 95% confidence intervals (CIs). <b><i>Results:</i></b> The meta-analysis included 1 RCT and 11 post hoc analyses of data from 10 double-blind placebo-controlled RCTs. Antiresorptive therapy significantly reduced the pooled incidence of vertebral fractures (RR = 0.43; 95% CI = 0.35–0.53; and <i>p</i> &#x3c; 0.001). It was also associated with lower risk of nonvertebral and hip fractures (RR = 0.84; 95% CI = 0.74–0.96; and <i>p</i> = 0.009 and RR = 0.75; 95% CI = 0.58–0.97; and <i>p</i> = 0.028, respectively). For any adverse events, no difference was observed between antiresorptive agents and placebo groups (RR = 1.01; 95% CI = 1.00–1.02; and <i>p</i> = 0.23). <b><i>Conclusions:</i></b> Both antiresorptive and anabolic agents represented potentially important osteoporosis treatments, showing significant effects on reducing vertebral, nonvertebral, or hip fracture risk, and were well-tolerated by elderly patients. Even in the elderly, maybe it is not too late to alter the course of the disease.

Mindfulness- and Acceptance-Based Interventions for Stroke Survivors: A Systematic Review and Meta-Analysis

2021 ◽  
pp. 003435522110432
Author(s):  
Areum Han
Keyword(s):  
Systematic Review ◽  
Depressive Symptoms ◽  
Meta Analysis ◽  
Random Effect ◽  
Random Effect Model ◽  
Mental Fatigue ◽  
Stroke Survivors ◽  
Positive Effects ◽  
Meta Analyses

Objective: Mindfulness- and acceptance-based intervention (MABI) is an emerging evidenced-based practice, but no systematic review incorporating meta-analyses for MABIs in stroke survivors has been conducted. The objective of this systematic review was to measure the effectiveness of MABIs on outcomes in people with stroke. Method: Three electronic databases, including PubMed, CINAHL, and PsycINFO, were searched to identify relevant studies published in peer-reviewed journals. The methodological quality of the included studies was assessed. Data were extracted and combined in a meta-analysis with a random-effect model to compute the size of the intervention effect. Results: A total of 11 studies met the eligibility criteria. Meta-analyses found a small-to-moderate effect of MABIs on depressive symptoms (standardized mean difference [SMD] = 0.39, 95% confidence interval [CI] = [0.12, 0.66]) and a large effect on mental fatigue (SMD = 1.22, 95% CI = [0.57, 1.87]). No statistically significant effect of MABIs on anxiety, quality of life, and mindfulness was found, but there was a trend in favor of MABIs overall. Conclusions: This meta-analysis found positive effects of MABIs on depressive symptoms and mental fatigue in stroke survivors, but future high-quality studies are needed to guarantee treatment effects of MABIs on varied outcomes in stroke survivors.

scholarly journals Association of AKAP6 and MIR2113 with cognitive performance in a population based sample of older adults

2016 ◽  
Author(s):  
Shea J. Andrews ◽  
Debjani Das ◽  
Kaarin J. Anstey ◽  
Simon Easteal
Keyword(s):  
Older Adults ◽  
Working Memory ◽  
Cognitive Function ◽  
Episodic Memory ◽  
Cognitive Performance ◽  
Cognitive Change ◽  
European Ancestry ◽  
Substantial Contribution ◽  
Perceptual Speed ◽  
Cognitive Domains

AbstractGenetic factors make a substantial contribution to inter-individual variability in cognitive function. A recent meta-analysis of genome-wide association studies identified two loci, AKAP6 and MIR2113 that are associated with general cognitive function. Here, we extend this previous research by investigating the association of MIR2113 and AKAP6 with baseline and longitudinal nonlinear change across a broad spectrum of cognitive domains in community-based cohort of 1,570 older adults without dementia. Two SNPs, MIR211-rs10457441 and AKAP6-rs17522122 were genotyped in 1,570 non-demented older Australians of European ancestry, who were examined up to 4 times over 12 years. Linear mixed effects models were used to examine the association between AKAP6 and MIR2113 with cognitive performance in episodic memory, working memory, vocabulary, perceptual speed and reaction time at baseline and with linear and quadratic rates of change. AKAP6-rs17522122*T was associated with worse baseline performance in episodic memory, working memory, vocabulary and perceptual speed, but it was not associated with cognitive change in any domain. MIR2113-rs10457441*T was associated with accelerated decline in episodic memory. No other associations with baseline cognitive performance or with linear or quadratic rate or cognitive changes was observed for this SNP. These results confirm the previous finding that, AKAP6 is associated with performance across multiple cognitive domains at baseline but not with cognitive decline, while MIR2113 primarily affects the rate at which memory declines over time.

scholarly journals Meta-Analysis on Cognitive Benefit of Exercise after Stroke

Complexity ◽  
2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Bo Yang ◽  
Shuming Wang
Keyword(s):  
Working Memory ◽  
Executive Function ◽  
Exercise Intervention ◽  
Combined Therapy ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Treatment Protocols ◽  
Cognitive Domains ◽  
Chi Squared ◽  
Cognitive Benefit

ObjectiveThe objective of this paper is to evaluate the cognitive benefit of exercise after stroke, so as to provide more accurate and reliable guidance for targeted exercise intervention. Methods. Randomized controlled trials of the relationship between exercise and cognition after stroke were identified in Cochrane Library and PubMed. Methodological quality was assessed using the Cochrane tool of bias. SMD and 95% confidence intervals were calculated, and Chi-squared test (Q) was adopted to estimate the heterogeneity. Results. (a) Twenty-three studies met inclusion criteria, including 1528 participants. Heterogeneity was from low to high such as attention (I2 = 0.00%), executive function (I2 = 0.00%), cognition (I2 = 64%), and working memory (I2 = 77%). (b) The overall effect on cognition was small (SMD = 0.16 [0.04, 0.28]) but significant and there is a difference between cognitive domains in attention (SMD = −0.35 [−0.57, −0.14]), executive function (SMD = −0.24 [−0.40, −0.08]), and working memory (SMD = 0.36 [0.20, 0.53]). (c) Exercise training was less effective before the 18th month after stroke. Higher benefits on cognition were found after combined therapy compared with other exercise programs, and the older the stroke survivors, the less the cognitive benefit of exercise. Conclusion. Small-to-moderate effect of exercise on cognitive benefit after stroke was found, and the effect was moderated by treatment protocols and sample characteristics.

scholarly journals Efficacy of non-invasive brain stimulation on cognitive functioning in brain disorders: a meta-analysis

2020 ◽  
Vol 50 (15) ◽  
pp. 2465-2486
Author(s):  
Marieke J. Begemann ◽  
Bodyl A. Brand ◽  
Branislava Ćurčić-Blake ◽  
André Aleman ◽  
Iris E. Sommer
Keyword(s):  
Working Memory ◽  
Brain Stimulation ◽  
Meta Analysis ◽  
Verbal Learning ◽  
The Other ◽  
Brain Disorders ◽  
Brain Disorder ◽  
Cognitive Domains ◽  
Domain Specific ◽  
Non Invasive

AbstractBackgroundCognition is commonly affected in brain disorders. Non-invasive brain stimulation (NIBS) may have procognitive effects, with high tolerability. This meta-analysis evaluates the efficacy of transcranial magnetic stimulation (TMS) and transcranial Direct Current Stimulation (tDCS) in improving cognition, in schizophrenia, depression, dementia, Parkinson's disease, stroke, traumatic brain injury, and multiple sclerosis.MethodsA PRISMA systematic search was conducted for randomized controlled trials. Hedges' g was used to quantify effect sizes (ES) for changes in cognition after TMS/tDCS v. sham. As different cognitive functions may have unequal susceptibility to TMS/tDCS, we separately evaluated the effects on: attention/vigilance, working memory, executive functioning, processing speed, verbal fluency, verbal learning, and social cognition.ResultsWe included 82 studies (n = 2784). For working memory, both TMS (ES = 0.17, p = 0.015) and tDCS (ES = 0.17, p = 0.021) showed small but significant effects. Age positively moderated the effect of TMS. TDCS was superior to sham for attention/vigilance (ES = 0.20, p = 0.020). These significant effects did not differ across the type of brain disorder. Results were not significant for the other five cognitive domains.ConclusionsOur results revealed that both TMS and tDCS elicit a small trans-diagnostic effect on working memory, tDCS also improved attention/vigilance across diagnoses. Effects on the other domains were not significant. Observed ES were small, yet even slight cognitive improvements may facilitate daily functioning. While NIBS can be a well-tolerated treatment, its effects appear domain specific and should be applied only for realistic indications (i.e. to induce a small improvement in working memory or attention).

scholarly journals Effects of SuperUlam on Supporting Concentration and Mood: A Randomized, Double-Blind, Placebo-Controlled Crossover Study

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Jay K Udani
Keyword(s):  
Working Memory ◽  
Reaction Time ◽  
Cognitive Function ◽  
Executive Functioning ◽  
Crossover Study ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Study Product ◽  
Total Mood Disturbance ◽  
Significant Difference

Background. SuperUlam is a proprietary blend of natural ingredients aimed at supporting brain health. We aimed to evaluate the effect of SuperUlam on attention and mood in healthy adults.Methods. Twenty healthy individuals aged 35–65 were enrolled in this randomized, double-blind, placebo-controlled, crossover study. Study duration was 3 weeks and consisted of 3 visits. Measurement of cognitive function included computer-based testing of reaction time, complex attention, working memory, sustained attention, and executive functioning. Mood testing was performed via the profile of mood states (POMS) survey and the Chalder fatigue scale.Results. Cognitive function testing demonstrated a significant improvement from baseline in executive functioning, cognitive flexibility, reaction time, and working memory in the product group only (P<0.05). When comparing the study product to placebo, the data demonstrated a significant decrease in tension, depression, and anger (P<0.05). There was no significant difference between the product and placebo in the other measures of mood, including vigor, fatigue, confusion, and total mood disturbance. No adverse events were reported.Conclusions.Supplementation with SuperUlam is safe to consume with potential benefits to cognitive function and mood.

Effects of acute tryptophan depletion on cognitive function in Alzheimer's disease and in the healthy elderly

2002 ◽  
Vol 33 (1) ◽  
pp. 41-49 ◽  
Author(s):  
R. J. PORTER ◽  
B. S. LUNN ◽  
J. T. O'BRIEN
Keyword(s):  
Cognitive Function ◽  
Rating Scales ◽  
Senile Dementia ◽  
Specific Effect ◽  
Acute Tryptophan Depletion ◽  
Elderly Subjects ◽  
Tryptophan Depletion ◽  
Emotional Symptoms ◽  
Double Blind ◽  
Healthy Elderly

Background. The cholinergic system is profoundly impaired in senile dementia of Alzheimer type (SDAT) and replacement therapy produces only modest clinical benefits. The serotonergic system is also impaired and may contribute both to cognitive and non-cognitive symptoms in SDAT. To investigate this further we assessed the effects of lowering brain serotonin using the technique of acute tryptophan depletion on cognitive function in patients with SDAT and in age matched control subjects.Method. Sixteen patients with probable SDAT and 17 healthy elderly subjects received two amino acid drinks in a within subject, double-blind, placebo-controlled, counterbalanced, crossover design. One of the drinks was nutritionally balanced and contained tryptophan (placebo), the other was identical but contained no tryptophan. A battery of detailed neuropsychological tests was performed between 4 and 6 h after the drink. Mood rating scales and other ratings of behavioural and emotional symptoms were also performed on both occasions.Results. Acute tryptophan depletion resulted in impairment on tasks of working memory in both groups. There was no group specific effect. Female SDAT subjects performed better on a task of pattern recognition during acute tryptophan depletion compared with placebo. There were no changes in behavioural symptoms during acute tryptophan depletion in either group.Conclusion. Compromised serotonergic function may be an important contributor to cognitive decline in SDAT and in ageing. Strategies targeting specific 5HT receptors may be helpful in SDAT.

Impact of Androgen-Deprivation Therapy on Cognitive Function in Men With Nonmetastatic Prostate Cancer

2010 ◽  
Vol 28 (34) ◽  
pp. 5030-5037 ◽  
Author(s):  
Shabbir M.H. Alibhai ◽  
Henriette Breunis ◽  
Narhari Timilshina ◽  
Shireen Marzouk ◽  
Diane Stewart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Working Memory ◽  
Cognitive Function ◽  
Androgen Deprivation Therapy ◽  
Verbal Memory ◽  
Visual Memory ◽  
Androgen Deprivation ◽  
Visuospatial Ability ◽  
Cognitive Domains ◽  
Immediate Memory

Purpose To evaluate the effects of androgen-deprivation therapy (ADT) on cognitive function in men with nonmetastatic prostate cancer (PC). Patients and Methods The following three groups of men age 50 years or older and matched on age and education were enrolled: patients with PC starting continuous ADT (n = 77), patients with PC not receiving ADT (PC controls, n = 82), and healthy controls (n = 82). A battery of 14 neuropsychological tests, examining eight cognitive domains, was administered at baseline, 6 months, and 12 months. Changes in cognitive scores over time were analyzed using the following three approaches: multivariable linear regression; the proportion of participants per group with 1 standard deviation (SD) or greater declines, and the proportion of participants who declined by at least 1.5 SD on two or more tests. Results The mean age and education level of participants were 68.9 years (range, 50 to 87 years) and 15.4 years of education (range, 8 to 24 years), respectively. Adjusted for age and education, all three cohorts had similar cognitive scores at baseline other than in one test of working memory. In adjusted regressions, ADT use was not associated with significant changes in the domains of attention/processing speed, verbal fluency, verbal memory, visual memory, or cognitive flexibility at either 6 months (all P > .05) or 12 months (all P > .05). One test each of immediate memory (P = .029), working memory (P = .031), and visuospatial ability (P = .034) were worse among ADT users than controls at 12 months, but these findings were not confirmed using other analytic approaches. Conclusion There is no consistent evidence that 12 months of ADT use has an adverse effect on cognitive function in elderly men with PC.

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