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

"Cerebellar Challenge" for Older Adults: Evaluation of a Home-Based Internet Intervention

There is converging evidence that maintenance of function in the multiple connectivity networks involving the cerebellum is a key requirement for healthy aging. The present study evaluated the effectiveness of a home-based, internet-administered “cerebellar challenge” intervention designed to create progressive challenges to vestibular function, multi-tasking, and dynamic coordination. Participants (n = 98, mean age 68.2, SD 6.6) were randomly allocated to either intervention (the cerebellar challenge training for 10 weeks) or no intervention. All participants undertook an initial series of pre-tests, and then an identical set of post-tests following the intervention period. The test battery comprised five suites of tests designed to evaluate cognitive-sensori-motor-affective functions, including Physical Coordination, Memory, Language Dexterity, Fluid Thinking and Affect. The intervention group showed significant pre- to post improvements in 9 of the 18 tests, whereas the controls improved significantly on one only. Furthermore, the intervention group showed significantly greater improvement than the controls on the “Physical Coordination” suite of tests, with evidence also of differential improvement on the Delayed Picture Recall test. Frequency of intervention use correlated significantly with the improvement in balance and in peg-moving speed. It is concluded that an internet-based cerebellar challenge programme for older adults can lead to benefits in balance, coordination and declarative memory. Limitations and directions for further research are outlined

Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise

Corrected by: Erratum: Molecular Psychiatry (2016) 21, 1645–1645; doi:10.1038/mp.2016.57; published online 19 April 2016. Following publication of the above article, the authors noticed that the second author’s name was presented incorrectly. The author’s name should have appeared as M Fiatarone Singh. The publisher regrets the error.Physical and cognitive exercise may prevent or delay dementia in later life but the neural mechanisms underlying these therapeutic benefits are largely unknown. We examined structural and functional magnetic resonance imaging (MRI) brain changes after 6 months of progressive resistance training (PRT), computerized cognitive training (CCT) or combined intervention. A total of 100 older individuals (68 females, average age=70.1, s.d.±6.7, 55-87 years) with dementia prodrome mild cognitive impairment were recruited in the SMART (Study of Mental Activity and Resistance Training) Trial. Participants were randomly assigned into four intervention groups: PRT+CCT, PRT+SHAM CCT, CCT+SHAM PRT and double SHAM. Multimodal MRI was conducted at baseline and at 6 months of follow-up (immediately after training) to measure structural and spontaneous functional changes in the brain, with a focus on the hippocampus and posterior cingulate regions. Participants' cognitive changes were also assessed before and after training. We found that PRT but not CCT significantly improved global cognition (F(90)=4.1, P<0.05) as well as expanded gray matter in the posterior cingulate (Pcorrected <0.05), and these changes were related to each other (r=0.25, P=0.03). PRT also reversed progression of white matter hyperintensities, a biomarker of cerebrovascular disease, in several brain areas. In contrast, CCT but not PRT attenuated decline in overall memory performance (F(90)=5.7, P<0.02), mediated by enhanced functional connectivity between the hippocampus and superior frontal cortex. Our findings indicate that physical and cognitive training depend on discrete neuronal mechanisms for their therapeutic efficacy, information that may help develop targeted lifestyle-based preventative strategies.Molecular Psychiatry advance online publication, 22 March 2016; doi:10.1038/mp.2016.19.C Suo, M Fiatarone Singh, N Gates, W Wen, P Sachdev, H Brodaty, N Saigal, GC Wilson, J Meiklejohn, N Singh, BT Baune, M Baker, N Foroughi, Y Wang, Y Mavros, A Lampit, I Leung, and MJ Valenzuel

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 &lt; 0.01) with between-study heterogeneity (τ2 = 0.217, I2 = 70.28%, p &lt; 0.001). The heterogeneity was partially explained by three moderators representing the in-between group differences of “maximum daily exercise” R2 = 33% (p &lt; 0.01), “type of cancer administration” R2 = 28% (p &lt; 0.05), and “training initiation” R2 = 27% (p &lt; 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

Let’s get physical (and cognitive): Fidelity and acceptability across a 12-week combined physical and cognitive training intervention

Background: Completing cognitive training alongside physical activity may be an effective and efficient way to improve cognitive performance. To inform ongoing randomized controlled trials (RCTs) investigating the efficacy of physical and cognitive training, intervention fidelity and participant experience should be considered. This study aimed to provide a comprehensive account of the interventions and participant experiences within a concurrent physical and cognitive training RCT. Methods: In total, 107 healthy active young adults were recruited for a 12-week investigator-blinded RCT. Participants were assigned to one of three intervention groups: 1) concurrent physical and cognitive training (twice-weekly steady-state stationary cycling plus simultaneous computerized cognitive training), 2) separate physical and cognitive training (twice-weekly steady-state stationary cycling plus twice-weekly computerized cognitive training performed at rest), or 3) physical-only training (twice-weekly steady-state stationary cycling). Measures of physical and perceived load were collected in weeks 3, 7, and 10, including power output, cadence, rating of perceived exertion (Borg’s 6-20 scale), the Physical Activity Enjoyment Scale, and NASA Task Load Index, were collected in weeks 3, 7, and 10 of the intervention. Cognitive training volume and intensity were collected for the concurrent and separate groups over the duration of the intervention. Measures of intervention acceptability included withdrawal rates and end-of-intervention participant feedback. Results: Participant attendance at training sessions was high (concurrent: 92±7%; separate: 96±6%; physical-only: 93±7%); with no difference between groups (p=0.220). There were no differences in physical load between groups; however, compared to the concurrent group, the separate group had a higher cognitive training volume (p=0.001) and intensity (p=0.002). Overall, participants from all groups reported that they enjoyed the physical training and experienced improvements in memory and focus from cognitive training. Conclusion: Concurrent physical and cognitive training appears to be a well-tolerated and time-efficient approach for investigating methods of improving cognitive performance in younger adults. Observations and recommendations from this study are provided to inform future research and interventions in this area

Auditory and cognitive training for cognition in adults with hearing loss: a systematic review and meta-analysis

This systematic review and meta-analysis examined the efficacy of auditory training and cognitive training to improve cognitive function in adults with hearing loss. A literature search of academic databases (e.g., MEDLINE, Scopus) and gray literature (e.g., OpenGrey) identified relevant articles published up to January 25, 2018. Randomized controlled trials (RCTs) or repeated measures designs were included. Outcome effects were computed as Hedge’s g and pooled using random-effects meta-analysis (PROSPERO: CRD42017076680). Nine studies, five auditory training, and four cognitive training met the inclusion criteria. Following auditory training, the pooled effect was small and statistically significant for both working memory (g = 0.21; 95% CI [0.05, 0.36]) and overall cognition (g = 0.19; 95% CI [0.07, 0.31]). Following cognitive training, the pooled effect for working memory was small and statistically significant (g = 0.34; 95% CI [0.16, 0.53]), and the pooled effect for overall cognition was large and significant (g = 1.03; 95% CI [0.41, 1.66]). However, this was dependent on the classification of training approach. Sensitivity analyses revealed no statistical difference between the effectiveness of auditory and cognitive training for improving cognition upon removal of a study that used a combined auditory–cognitive approach, which showed a very large effect. Overall certainty in the estimation of effect was “low” for auditory training and “very low” for cognitive training. High-quality RCTs are needed to determine which training stimuli will provide optimal conditions to improve cognition in adults with hearing loss

Cognitive Reserve and the Prevention of Dementia: the Role of Physical and Cognitive Activities

Purpose of Review: The article discusses the two most significant modifiable risk factors for dementia, namely, physical inactivity and lack of stimulating cognitive activity, and their effects on developing cognitive reserve. Recent Findings: Both of these leisure-time activities were associated with significant reductions in the risk of dementia in longitudinal studies. In addition, physical activity, particularly aerobic exercise, is associated with less age-related gray and white matter loss and with less neurotoxic factors. On the other hand, cognitive training studies suggest that training for executive functions (e.g., working memory) improves prefrontal network efficiency, which provides support to brain functioning in the face of cognitive decline. Summary: While physical activity preserves neuronal structural integrity and brain volume (hardware), cognitive activity strengthens the functioning and plasticity of neural circuits (software), thus supporting cognitive reserve in different ways. Future research should examine whether lifestyle interventions incorporating these two domains can reduce incident dementia

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

Risk factors for delirium and cognitive decline following coronary artery bypass grafting surgery: a systematic review and meta-analysis

Background: Coronary artery bypass grafting (CABG) is known to improve heart function and quality of life, while rates of surgery-related mortality are low. However, delirium and cognitive decline are common complications. We sought to identify preoperative, intraoperative, and postoperative risk or protective factors associated with delirium and cognitive decline (across time) in patients undergoing CABG. Methods and Results: We conducted a systematic search of Medline, PsycINFO, EMBASE, and Cochrane (March 26, 2019) for peer-reviewed, English publications reporting post-CABG delirium or cognitive decline data, for at least one risk factor. Random-effects meta-analyses estimated pooled odds ratio for categorical data and mean difference or standardized mean difference for continuous data. Ninety-seven studies, comprising data from 60 479 patients who underwent CABG, were included. Moderate to large and statistically significant risk factors for delirium were as follows: (1) preoperative cognitive impairment, depression, stroke history, and higher European System for Cardiac Operative Risk Evaluation (EuroSCORE) score, (2) intraoperative increase in intubation time, and (3) postoperative presence of arrythmia and increased days in the intensive care unit; higher preoperative cognitive performance was protective for delirium. Moderate to large and statistically significant risk factors for acute cognitive decline were as follows: (1) preoperative depression and older age, (2) intraoperative increase in intubation time, and (3) postoperative presence of delirium and increased days in the intensive care unit. Presence of depression preoperatively was a moderate risk factor for midterm (1–6 months) post-CABG cognitive decline. Conclusions: This meta-analysis identified several key risk factors for delirium and cognitive decline following CABG, most of which are nonmodifiable. Future research should target preoperative risk factors, such as depression or cognitive impairment, which are potentially modifiable.Danielle Greaves, Peter J. Psaltis, Daniel H.J. Davis, Tyler J. Ross, Erica S. Ghezzi, Amit Lampit, Ashleigh E. Smith, Hannah A.D. Keag