Computerised cognitive training to improve cognition including delirium following coronary artery bypass grafting surgery: protocol for a blinded randomised controlled trial

INTRODUCTION:Coronary artery bypass grafting (CABG) surgery is known to improve vascular function and cardiac-related mortality rates; however, it is associated with high rates of postoperative cognitive decline and delirium. Previous attempts to prevent post-CABG cognitive decline using pharmacological and surgical approaches have been largely unsuccessful. Cognitive prehabilitation and rehabilitation are a viable yet untested option for CABG patients. We aim to investigate the effects of preoperative cognitive training on delirium incidence, and preoperative and postoperative cognitive training on cognitive decline at 4 months post-CABG. METHODS AND ANALYSIS:This study is a randomised, single-blinded, controlled trial investigating the use of computerised cognitive training (CCT) both pre-CABG and post-CABG (intervention group) compared with usual care (control group) in older adults undergoing CABG in Adelaide, South Australia. Those in the intervention group will complete 1-2 weeks of CCT preoperatively (45-60 min sessions, 3.5 sessions/week) and 12 weeks of CCT postoperatively (commencing 1 month following surgery, 45-60 min sessions, 3 sessions/week). All participants will undergo cognitive testing preoperatively, over their hospital stay including delirium, and postoperatively for up to 1 year. The primary delirium outcome variable will be delirium incidence (presence vs absence); the primary cognitive decline variable will be at 4 months (significant decline vs no significant decline/improvement from baseline). Logistic regression modelling will be used, with age and gender as covariates. Secondary outcomes include cognitive decline from baseline to discharge, and at 6 months and 1 year post-CABG. ETHICS AND DISSEMINATION:Ethics approval was obtained from the Central Adelaide Local Health Network Human Research Ethics Committee (South Australia, Australia) and the University of South Australia Human Ethics Committee, with original approval obtained on 13 December 2017. It is anticipated that approximately two to four publications and multiple conference presentations (national and international) will result from this research. TRIAL REGISTRATION NUMBER:This clinical trial is registered with the Australian New Zealand Clinical Trials Registry and relates to the pre-results stage. Registration number: ACTRN12618000799257.Danielle Greaves, Peter J Psaltis, Amit Lampit, Daniel H J Davis, Ashleigh E Smith ... Hannah A D Keage ... et al

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

Toward a theory‐based specification of non‐pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations

INTRODUCTION: Non-pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. METHODS: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. RESULTS: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. DISCUSSION: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area

Toward a theory‐based specification of non‐pharmacological treatments in aging and dementia: Focused reviews and methodological recommendations

Introduction: Non‐pharmacological treatments (NPTs) have the potential to improve meaningful outcomes for older people at risk of, or living with dementia, but research often lacks methodological rigor and continues to produce mixed results. Methods: In the current position paper, experts in NPT research have specified treatment targets, aims, and ingredients using an umbrella framework, the Rehabilitation Treatment Specification System. Results: Experts provided a snapshot and an authoritative summary of the evidence for different NPTs based on the best synthesis efforts, identified main gaps in knowledge and relevant barriers, and provided directions for future research. Experts in trial methodology provide best practice principles and recommendations for those working in this area, underscoring the importance of prespecified protocols. Discussion: We conclude that the evidence strongly supports various NPTs in relation to their primary targets, and discuss opportunities and challenges associated with a unifying theoretical framework to guide future efforts in this area

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

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

Does working memory training have to be adaptive?

This study tested the common assumption that, to be most effective, working memory (WM) training should be adaptive (i.e., task difficulty is adjusted to individual performance). Indirect evidence for this assumption stems from studies comparing adaptive training to a condition in which tasks are practiced on the easiest level of difficulty only [cf. Klingberg (Trends Cogn Sci 14:317-324, 2010)], thereby, however, confounding adaptivity and exposure to varying task difficulty. For a more direct test of this hypothesis, we randomly assigned 130 young adults to one of the three WM training procedures (adaptive, randomized, or self-selected change in training task difficulty) or to an active control group. Despite large performance increases in the trained WM tasks, we observed neither transfer to untrained structurally dissimilar WM tasks nor far transfer to reasoning. Surprisingly, neither training nor transfer effects were modulated by training procedure, indicating that exposure to varying levels of task difficulty is sufficient for inducing training gains

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

Novelty, challenge, and practice:The impact of intensive language learning on attentional functions

We investigated the impact of a short intensive language course on attentional functions. We examined 33 participants of a one-week Scottish Gaelic course and compared them to 34 controls: 16 active controls who participated in courses of comparable duration and intensity but not involving foreign language learning and 18 passive controls who followed their usual routines. Participants completed auditory tests of attentional inhibition and switching. There was no difference between the groups in any measures at the beginning of the course. At the end of the course, a significant improvement in attention switching was observed in the language group (p < .001) but not the control group (p = .127), independent of the age of participants (18-78 years). Half of the language participants (n = 17) were retested nine months after their course. All those who practiced Gaelic 5 hours or more per week improved from their baseline performance. In contrast, those who practiced 4 hours or fewer showed an inconsistent pattern: some improved while others stayed the same or deteriorated. Our results suggest that even a short period of intensive language learning can modulate attentional functions and that all age groups can benefit from this effect. Moreover, these short-term effects can be maintained through continuous practice

Recent Advances in Preventing and Managing Postoperative Delirium [version 1; peer review: 2 approved]

Postoperative delirium is a common and harrowing complication in older surgical patients. Those with cognitive impairment or dementia are at especially high risk for developing postoperative delirium; ominously, it is hypothesized that delirium can accelerate cognitive decline and the onset of dementia, or worsen the severity of dementia. Awareness of delirium has grown in recent years as various medical societies have launched initiatives to prevent postoperative delirium and alleviate its impact. Unfortunately, delirium pathophysiology is not well understood and this likely contributes to the current state of low-quality evidence that informs perioperative guidelines. Along these lines, recent prevention trials involving ketamine and dexmedetomidine have demonstrated inconsistent findings. Non-pharmacologic multicomponent initiatives, such as the Hospital Elder Life Program, have consistently reduced delirium incidence and burden across various hospital settings. However, a substantial portion of delirium occurrences are still not prevented, and effective prevention and management strategies are needed to complement such multicomponent non-pharmacologic therapies. In this narrative review, we examine the current understanding of delirium neurobiology and summarize the present state of prevention and management efforts