Amit Lampit

Cognitive training in Parkinson disease A systematic review and meta-analysis

Objective: To quantify the effects of cognitive training (CT) on cognitive and behavioral outcome measures in patients with Parkinson disease (PD). Methods: We systematically searched 5 databases for randomized controlled trials (RCTs) of CT in patients with PD reporting cognitive or behavioral outcomes. Efficacy was measured as standardized mean difference (Hedges g) of post-training change. Results: Seven studies encompassing 272 patients with Hoehn & Yahr Stages 1–3 were included. The overall effect of CT over and above control conditions was small but statistically significant (7 studies: g = 0.23, 95% confidence interval [CI] 0.014–0.44, p = 0.037). True heterogeneity across studies was low (I2 = 0%) and there was no evidence of publication bias. Larger effect sizes were noted on working memory (4 studies: g = 0.74, CI 0.32–1.17, p = 0.001), processing speed (4 studies: g = 0.31, CI 0.01–0.61, p = 0.04), and executive function (5 studies: g = 0.30, CI 0.01–0.58, p = 0.042), while effects on measures of global cognition (4 studies), memory (5 studies), visuospatial skills (4 studies), and depression (5 studies), as well as attention, quality of life, and instrumental activities of daily living (3 studies each), were not statistically significant. No adverse events were reported. Conclusions: Though still small, the current body of RCT evidence indicates that CT is safe and modestly effective on cognition in patients with mild to moderate PD. Larger RCTs are necessary to examine the utility of CT for secondary prevention of cognitive decline in this population.

Cognitive training-induced short-term functional and long-term structural plastic change is related to gains in global cognition in healthy older adults: a pilot study.

Computerized cognitive training (CCT) is a safe and inexpensive intervention to enhance cognitive performance in the elderly. However, the neural underpinning of CCT-induced effects and the timecourse by which such neural changes occur are unknown. Here, we report on results from a pilot study of healthy older adults who underwent three 1-h weekly sessions of either multidomain CCT program (n = 7) or an active control intervention (n = 5) over 12 weeks. Multimodal magnetic resonance imaging (MRI) scans and cognitive assessments were performed at baseline and after 9 and 36 h of training. Voxel-based structural analysis revealed a significant Group × Time interaction in the right post-central gyrus indicating increased gray matter density in the CCT group compared to active control at both follow-ups. Across the entire sample, there were significant positive correlations between changes in the post-central gyrus and change in global cognition after 36 h of training. A post-hoc vertex-based analysis found a significant between-group difference in rate of thickness change between baseline and post-training in the left fusiform gyrus, as well as a large cluster in the right parietal lobe covering the supramarginal and post-central gyri. Resting-state functional connectivity between the posterior cingulate and the superior frontal gyrus, and between the right hippocampus and the superior temporal gyrus significantly differed between the two groups after 9 h of training and correlated with cognitive change post-training. No significant interactions were found for any of the spectroscopy and diffusion tensor imaging data. Though preliminary, our results suggest that functional change may precede structural and cognitive change, and that about one-half of the structural change occurs within the first 9 h of training. Future studies are required to determine the role of these brain changes in the mechanisms underlying CCT-induced cognitive effects.

Predictors of placebo response in pharmacological and dietary supplement treatment trials in pediatric autism spectrum disorder: a meta-analysis

Large placebo responses in many clinical trials limit our capacity to identify effective therapeutics. Although it is often assumed that core behaviors in children with autism spectrum disorders (ASDs) rarely remit spontaneously, there has been limited investigation of the size of the placebo response in relevant clinical trials. These trials also rely on caregiver and clinical observer reports as outcome measures. The objectives of this meta-analysis are to identify the pooled placebo response and the predictors of placebo response in pharmacological and dietary supplement treatment trials for participants with a diagnosis of ASD. Randomized controlled trials (RCTs) in pediatric ASD, conducted between 1980 and August 2014, were identified through a search of Medline, EMBASE, Web of Science, Cochrane Database of Systematic Reviews and clinicaltrials.gov. RCTs of at least 14 days duration, comparing the treatment response for an oral active agent and placebo using at least one of the common outcome measures, were included. Analysis of 25 data sets (1315 participants) revealed a moderate effect size for overall placebo response (Hedges’ g=0.45, 95% confidence interval (0.34–0.56), P<0.001). Five factors were associated with an increase in response to placebo, namely: an increased response to the active intervention; outcome ratings by clinicians (as compared with caregivers); trials of pharmacological and adjunctive interventions; and trials located in Iran. There is a clear need for the identification of objective measures of change in clinical trials for ASD, such as evaluation of biological activity or markers, and for consideration of how best to deal with placebo response effects in trial design and analyses.

Autism spectrum disorders: a meta-analysis of executive function

Evidence of executive dysfunction in autism spectrum disorders (ASD) across development remains mixed and establishing its role is critical for guiding diagnosis and intervention. The primary objectives of this meta-analysis is to analyse executive function (EF) performance in ASD, the fractionation across EF subdomains, the clinical utility of EF measures and the influence of multiple moderators (for example, age, gender, diagnosis, measure characteristics). The Embase, Medline and PsychINFO databases were searched to identify peer-reviewed studies published since the inclusion of Autism in DSM-III (1980) up to end of June 2016 that compared EF in ASD with neurotypical controls. A random-effects model was used and moderators were tested using subgroup analysis. The primary outcome measure was Hedges’ g effect size for EF and moderator factors. Clinical sensitivity was determined by the overlap percentage statistic (OL%). Results were reported according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 235 studies comprising 14 081 participants were included (N, ASD=6816, Control=7265). A moderate overall effect size for reduced EF (Hedges’ g=0.48, 95% confidence interval (CI) 0.43–0.53) was found with similar effect sizes across each domain. The majority of moderator comparisons were not significant although the overall effect of executive dysfunction has gradually reduced since the introduction of ASD. Only a small number of EF measures achieved clinical sensitivity. This study confirms a broad executive dysfunction in ASD that is relatively stable across development. The fractionation of executive dysfunction into individual subdomains was not supported, nor was diagnostic sensitivity. Development of feasible EF measures focussing on clinical sensitivity for diagnosis and treatment studies should be a priority.

Computerized Cognitive Training Is Beneficial for Older Adults

Research efforts to determine whether computerized cognitive training (CCT) benefits cognition in older adults have spanned more than two decades and dozens of randomized controlled trials (RCTs) encompassing thousands of participants. The wealth of evidence from such trials allows us to determine not only whether CCT is an efficacious intervention to improve cognition, but also what cognitive domains are likely to respond and what training regimens are likely to yield the greatest effects. Despite this empirical database, the efficacy of CCT remains controversial in the scientific community, and both sides of the debate encourage further research. In our opinion, the “brain training debate” has become a vehicle for point scoring rather than productive evaluation of a cognitive intervention. Ideally, research should focus on establishing a coherent research agenda for clinical implementation and developing guidelines for regulation of commercial products as medical devices under federal law.

Cognitive Training for Post-Acute Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Objective: To quantitatively aggregate effects of cognitive training (CT) on cognitive and functional outcome measures in patients with traumatic brain injury (TBI) more than 12-months post-injury. Design: We systematically searched six databases for non-randomized and randomized controlled trials of CT in TBI patients at least 12-months post-injury reporting cognitive and/or functional outcomes. Main Measures: Efficacy was measured as standardized mean difference (Hedges’ g) of post-training change. We investigated heterogeneity across studies using subgroup analyses and meta-regressions. Results: Fourteen studies encompassing 575 patients were included. The effect of CT on overall cognition was small and statistically significant (g = 0.22, 95%CI 0.05 to 0.38; p = 0.01), with low heterogeneity (I2 = 11.71%) and no evidence of publication bias. A moderate effect size was found for overall functional outcomes (g = 0.32, 95%CI 0.08 to 0.57, p = 0.01) with low heterogeneity (I2 = 14.27%) and possible publication bias. Statistically significant effects were also found only for executive function (g = 0.20, 95%CI 0.02 to 0.39, p = 0.03) and verbal memory (g = 0.32, 95%CI 0.14 to 0.50, p < 0.01). Conclusion: Despite limited studies in this field, this meta-analysis indicates that CT is modestly effective in improving cognitive and functional outcomes in patients with post-acute TBI and should therefore play a more significant role in TBI rehabilitation.

Is Obstructive Sleep Apnoea Related to Neuropsychological Function in Healthy Older Adults? A Systematic Review and Meta-Analysis

Previous systematic reviews and meta-analyses have identified cognitive deficits in adults with obstructive sleep apnoea (OSA). However, quantitative analysis of the association between OSA and neuropsychological performance has not been conducted specifically in older adults, for whom there is a greater risk of cognitive decline. We searched Medline, Embase and PsycINFO through August 2016 for studies describing associations between OSA and neuropsychological outcomes in people aged>50 years. Meta-analyses were performed on these studies for overall cognition and within cognitive domains. Subgroup analyses were performed taking into account risk of bias and moderating differences in study design. 13 studies met eligibility criteria for analysis. A small negative association was found between OSA and all neuropsychological outcomes combined, g=0.18(95% CI 0.04–0.32), and in memory and processing speed domains. Small case-control studies from sleep clinic populations observed the greatest associations, while larger cohort studies from community samples illustrated no association. Analysis accounting for publication bias resulted in a null overall association, g=0.02 (95%CI -0.12 to 0.16). Associations between OSA and cognition in later life are highly variable and the findings differ based on the type and setting of study. It appears some older adults may be at risk of cognitive impairments attributable to OSA; however, the risk of bias renders the evidence inconclusive. High quality research is warranted in clinically diagnosed OSA patients as well as those already experiencing neuropsychological impairment and who may be regarded at higher risk of further cognitive decline.

Effectiveness of eHealth interventions for reducing mental health conditions in employees: A systematic review and meta-analysis

Background Many organisations promote eHealth applications as a feasible, low-cost method of addressing mental ill-health and stress amongst their employees. However, there are good reasons why the efficacy identified in clinical or other samples may not generalize to employees, and many Apps are being developed specifically for this group. The aim of this paper is to conduct the first comprehensive systematic review and meta-analysis evaluating the evidence for the effectiveness and examine the relative efficacy of different types of eHealth interventions for employees. Methods Systematic searches were conducted for relevant articles published from 1975 until November 17, 2016, of trials of eHealth mental health interventions (App or web-based) focused on the mental health of employees. The quality and bias of all identified studies was assessed. We extracted means and standard deviations from published reports, comparing the difference in effect sizes (Hedge’s g) in standardized mental health outcomes. We meta-analysed these using a random effects model, stratified by length of follow up, intervention type, and whether the intervention was universal (unselected) or targeted to selected groups e.g. “stressed”. Results 23 controlled trials of eHealth interventions were identified which overall suggested a small positive effect at both post intervention (g = 0.24, 95% CI 0.13 to 0.35) and follow up (g = 0.23, 95% CI 0.03 to 0.42). There were differential short term effects seen between the intervention types whereby Mindfulness based interventions (g = 0.60, 95% CI 0.34 to 0.85, n = 6) showed larger effects than the Cognitive Behaviour Therapy (CBT) based (g = 0.15, 95% CI 0.02 to 0.29, n = 11) and Stress Management based (g = 0.17, 95%CI -0.01 to 0.34, n = 6) interventions. The Stress Management interventions however differed by whether delivered to universal or targeted groups with a moderately large effect size at both post-intervention (g = 0.64, 95% CI 0.54 to 0.85) and follow-up (g = 0.69, 95% CI 0.06 to 1.33) in targeted groups, but no effect in unselected groups. Interpretation There is reasonable evidence that eHealth interventions delivered to employees may reduce mental health and stress symptoms post intervention and still have a benefit, although reduced at follow-up. Despite the enthusiasm in the corporate world for such approaches, employers and other organisations should be aware not all such interventions are equal, many lack evidence, and achieving the best outcomes depends upon providing the right type of intervention to the correct population.

Meta-Analysis of the Effects of Computerized Cognitive Training on Executive Functions: a Cross-Disciplinary Taxonomy for Classifying Outcome Cognitive Factors

The growing prevalence of neurodegenerative disorders associated with aging and cognitive decline has generated increasing cross-disciplinary interest in non-pharmacological interventions, such as computerized cognitive training (CCT), which may prevent or slow cognitive decline. However, inconsistent findings across meta-analytic reviews in the field suggest a lack of cross-disciplinary consensus and on-going debate regarding the benefits of CCT. We posit that a contributing factor is the lack of a theoretically-based taxonomy of constructs and representative tasks typically used. An integration of the Cattell-Horn-Carroll (CHC) taxonomy of broad and narrow cognitive factors and the Miyake unity-diversity theory of executive functions (EF) is proposed (CHC-M) as an attempt to clarify this issue through representing and integrating the disciplines contributing to CCT research. The present study assessed the utility of this taxonomy by reanalyzing the Lampit et al. (2014) meta-analysis of CCT in healthy older adults using the CHC-M framework. Results suggest that: 1) substantively different statistical effects are observed when CHC-M is applied to the Lampit et al. meta-analytic review, leading to importantly different interpretations of the data; 2) typically-used classification practices conflate Executive Function (EF) tasks with fluid reasoning (Gf) and retrieval fluency (Gr), and Attention with sensory perception; and 3) there is theoretical and practical advantage in differentiating attention and working-memory tasks into the narrow shifting, inhibition, and updating EF domains. Implications for clinical practice, particularly for our understanding of EF are discussed.

Computerised Training Improves Cognitive Performance in Chronic Pain: A Participant-Blinded Randomised Active-Controlled Trial with Remote Supervision

Abstract Chronic pain is associated with reduced efficiency of cognitive performance, and few studies have investigated methods of remediation. We trialled a computerised cognitive training protocol to determine whether it could attenuate cognitive difficulties in a chronic pain sample. Thirty-nine adults with chronic pain (mean age = 43.3, 61.5% females) were randomised to an 8-week online course (3 sessions/week from home) of game-like cognitive training exercises, or an active control involving watching documentary videos. Participants received weekly supervision by video call. Primary outcomes were a global neurocognitive composite (tests of attention, speed, and executive function) and self-reported cognition. Secondary outcomes were pain (intensity; interference), mood symptoms (depression; anxiety), and coping with pain (catastrophising; self-efficacy). Thirty participants (15 training and 15 control) completed the trial. Mixed model intention-to-treat analyses revealed significant effects of training on the global neurocognitive composite (net effect size [ES] = 0.43, P = 0.017), driven by improved executive function performance (attention switching and working memory). The control group reported improvement in pain intensity (net ES = 0.65, P = 0.022). Both groups reported subjective improvements in cognition (ES = 0.28, P = 0.033) and catastrophising (ES = 0.55, P = 0.006). Depression, anxiety, self-efficacy, and pain interference showed no change in either group. This study provides preliminary evidence that supervised cognitive training may be a viable method for enhancing cognitive skills in persons with chronic pain, but transfer to functional and clinical outcomes remains to be demonstrated. Active control results suggest that activities perceived as relaxing or enjoyable contribute to improved perception of well-being. Weekly contact was pivotal to successful program completion.