Timecourse of Cognitive and Brain Adaptation to Cognitive Training in At-risk Elderly

Maintaining cognitive ability in the elderly is a global priority. Computerised cognitive training (CCT) is among the few effective interventions but the boundaries and mechanisms underlying its effectiveness are largely unknown. Chapter 2 is the first systematic review and meta-analysis of 37 randomised controlled trials (RCTs) of CCT in healthy elderly, encompassing a total of 4,310 participants. CCT was effective on all the cognitive domains except for executive functions. Type of training program, mode of delivery, session length and training frequency were found to moderate CCT efficacy. The Timecourse Trial (Chapter 3) was a randomized, double-blind, active controlled longitudinal trial of CCT in 80 healthy elderly. Significant effects were found on global cognition, memory and processing speed, and dose-response curves differed across domains. These domain-specific gains also followed different decay curves after training cessation throughout the 12 months follow-up period. Chapter 4 investigates the neural underpinnings of gains in global cognition. Modification of resting-state functional connectivity was found to predict subsequent cognitive gains, gains that were also correlated to structural cortical plasticity. CCT is an effective intervention in the elderly. The field may do well to now focus on improving standards, large-scale trials and a further understanding of biological mechanisms

Impact of Physical Exercise on Growth and Progression of Cancer in Rodents—A Systematic Review and Meta-Analysis

Background: Physical exercise is suspected to reduce cancer risk and mortality. So far, little is known about the underlying mechanisms. Although limited, murine models represent a promising attempt in order to gain knowledge in this field.Objective: A systematic review and meta-analysis examining various treatment protocols was conducted in order to determine the impact of exercise on tumor growth in rodents.Methods: PubMed, Google scholar and System for information on Gray literature in Europe were screened from inception to October 2017. Risk of bias within individual studies was assessed using the Office of Health Assessment and Translation risk of bias rating tool for human and animal trials. The effect of exercise on tumor growth over and above non-exercise control was pooled using random-effects model. Subgroup analyses were conducted to identify potential moderators.Results: The quality of the included 17 articles ranged between “probably low” and “high risk of bias.” A significant reduction in tumor growth in exercising animals compared to controls was detected (Hedges' g = −0.40; 95% CI −0.66 to −0.14, p < 0.01) with between-study heterogeneity (τ2 = 0.217, I2 = 70.28%, p < 0.001). The heterogeneity was partially explained by three moderators representing the in-between group differences of “maximum daily exercise” R2 = 33% (p < 0.01), “type of cancer administration” R2 = 28% (p < 0.05), and “training initiation” R2 = 27% (p < 0.05).Conclusion: This meta-analysis suggests that physical exercise leads to reduction of tumor size in rodents. Since “maximum daily exercise” was found to have at least modest impact on tumor growth, more clinical trials investigating dose-response relationships are needed

The effects of computerised cognitive training on post-CABG delirium and cognitive change: A prospective randomised controlled trial

Background: Cognitive impairments, including delirium, are common after coronary artery bypass grafting (CABG). Improving cognition pre- and post-operatively using computerised cognitive training (CCT) may be an effective approach to improve cognitive outcomes in CABG patients. Objectives: Investigate the effect of remotely supervised CCT on cognitive outcomes, including delirium, in older adults undergoing CABG surgery. Methods: Thirty-six participants, were analysed in a single-blinded randomised controlled trial (CCT Intervention: n = 18, Control: n = 18). CCT was completed by the intervention group pre-operatively (every other day, 45–60-minute sessions until surgery) and post-operatively, beginning 1-month post-CABG (3 x 45–60-minute sessions/week for 12-weeks), while the control group maintained usual care plus weekly phone calls. Cognitive assessments were conducted pre- and post-operatively at multiple follow-ups (discharge, 4-months and 6-months). Post-operative delirium incidence was assessed daily until discharge. Cognitive change data were calculated at each follow-up for each cognitive test (Addenbrooke’s Cognitive Examination III and CANTAB; z-scored). Results: Adherence to the CCT intervention (completion of three pre-operative or 66% of post-operative sessions) was achieved in 68% of pre-CABG and 59% of post-CABG participants. There were no statistically significant effects of CCT on any cognitive outcome, including delirium incidence. Conclusion: Adherence to the CCT program was comparatively higher than previous feasibility studies, possibly due to the level of supervision and support provided (blend of face-to-face and home-based training, with support phone calls). Implementing CCT interventions both pre- and post-operatively is feasible in those undergoing CABG. No statistically significant benefits from the CCT interventions were identified for delirium or cognitive function post-CABG, likely due to the sample size available (study recruitment greatly impacted by COVID-19). It also may be the case that multimodal intervention would be more effective

Multidisciplinary rehabilitation reduces hypothalamic grey matter volume loss in individuals with preclinical Huntington's disease: A nine-month pilot study

Background: Hypothalamic pathology is a well-documented feature of Huntington's disease (HD) and is believed to contribute to circadian rhythm and habitual sleep disturbances. Currently, no therapies exist to combat hypothalamic changes, nor circadian rhythm and habitual sleep disturbances in HD. Objective: To evaluate the effects of multidisciplinary rehabilitation on hypothalamic volume, brain-derived neurotrophic factor (BDNF), circadian rhythm and habitual sleep in individuals with preclinical HD. Methods: Eighteen individuals with HD (ten premanifest and eight prodromal) undertook a nine-month multidisciplinary rehabilitation intervention (intervention group), which included exercise, cognitive and dual task training and social events, and were compared to a community sample of eleven individuals with premanifest HD receiving no intervention (control group). Hypothalamic volume, serum BDNF, salivary cortisol and melatonin concentrations, subjective sleep quality, daytime somnolence, habitual sleep-wake patterns, stress and anxiety and depression symptomatology were evaluated. Results: Hypothalamus grey matter volume loss was significantly attenuated in the intervention group compared to the control group after controlling for age, gender, Unified Huntington's Disease Rating Scale-Total Motor Score and number of cytosine-adenine-guanine repeats. Serum BDNF levels were maintained in the intervention group, but decreased in the control group following the study period. Both groups exhibited decreases in cortisol and melatonin concentrations. No changes were observed in sleep or mood outcomes. Conclusions: This exploratory study provides evidence that multidisciplinary rehabilitation can reduce hypothalamic volume loss and maintain peripheral BDNF levels in individuals with preclinical HD but may not impact on circadian rhythm. Larger, randomised controlled trials are required to confirm these findings

Effect of multidisciplinary rehabilitation on sleep outcomes in individuals with preclinical Huntington disease: An exploratory study

Dear Editor Sleep disturbances are an early feature of Huntington disease (HD), which worsen as the disease progresses. Studies have documented increased sleep fragmentation, decreased rapid eye-movement (REM) sleep, reduced sleep efficiency, insomnia and an increase in periodic leg movements (PLMs) in individuals with HD [1], [2]. Disturbances in sleep are thought to exacerbate cognitive impairments and may hasten subcortical neurodegeneration [3], [4]. Hence, management of sleep disturbances in individuals with HD is imperative

Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers

<div><p>Background</p><p>New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.</p><p>Methods and Findings</p><p>We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (<i>I</i>² = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' <i>g</i>, random effects model) for CCT versus control was small and statistically significant, <i>g</i> = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, <i>g</i> = 0.24 (95% CI 0.09 to 0.38); verbal memory, <i>g</i> = 0.08 (95% CI 0.01 to 0.15); working memory (WM), <i>g</i> = 0.22 (95% CI 0.09 to 0.35); processing speed, <i>g</i> = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, <i>g</i> = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.</p><p>Conclusions</p><p>CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention.</p><p><i>Please see later in the article for the Editors' Summary</i></p></div

Efficacy of CCT on measures of executive functions.

<p>Effect estimates are based on a random-effects model, and studies are rank-ordered by year of publication.</p

Efficacy of CCT on measures of verbal memory.

<p>Effect estimates are based on fixed-effects (top) and random-effects (bottom) models, and studies are rank-ordered by year of publication.</p

Efficacy of CCT on measures of working memory.

<p>Effect estimates are based on a random-effects model, and studies are rank-ordered by year of publication.</p

Overview of efficacy and moderators of efficacy for CCT in older adults.

<p>Numbers refer to SMDs from an individual meta-analysis (see <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s002" target="_blank">Figures S2</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s003" target="_blank">S3</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s004" target="_blank">S4</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s005" target="_blank">S5</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s006" target="_blank">S6</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s007" target="_blank">S7</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s008" target="_blank">S8</a> for details). Colored cells indicate significant outcomes, with effect sizes color coded: yellow, <i>g</i><0.3; pink, <i>g</i> = 0.3–0.6; red, <i>g</i>≥0.6. White depicts non-significant results, and grey shows where no studies were available for analysis. *<i>p</i><0.05, **<i>p</i><0.01 for within-subgroup results (between-subgroup results are reported in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed-1001756-g011" target="_blank">Figures 11</a> and <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s002" target="_blank">S2</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s003" target="_blank">S3</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s004" target="_blank">S4</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s005" target="_blank">S5</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s006" target="_blank">S6</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s007" target="_blank">S7</a>, <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001756#pmed.1001756.s008" target="_blank">S8</a>). ^aBased on a fixed-effects model because of evidence of potential publication bias in these outcomes. ^bSMD based on a single trial.</p