Improving Recovery and Outcomes Every Day after the ICU (IMPROVE): study protocol for a randomized controlled trial.
ABSTRACT: BACKGROUND:Delirium affects nearly 70% of older adults hospitalized in the intensive care unit (ICU), and many of those will be left with persistent cognitive impairment or dementia. There are no effective and scalable recovery models to remediate ICU-acquired cognitive impairment and its attendant elevated risk for dementia or Alzheimer disease (AD). The Improving Recovery and Outcomes Every Day after the ICU (IMPROVE) trial is an ongoing clinical trial which evaluates the efficacy of a combined physical exercise and cognitive training on cognitive function among ICU survivors 50 years and older who experienced delirium during an ICU stay. This article describes the study protocol for IMPROVE. METHODS:IMPROVE is a four-arm, randomized controlled trial. Subjects will be randomized to one of four arms: cognitive training and physical exercise; cognitive control and physical exercise; cognitive training and physical exercise control; and cognitive control and physical exercise control. Facilitators administer the physical exercise and exercise control interventions in individual and small group formats by using Internet-enabled videoconference. Cognitive training and control interventions are also facilitator led using Posit Science, Inc. online modules delivered in individual and small group format directly into the participants' homes. Subjects complete cognitive assessment, mood questionnaires, physical performance batteries, and quality of life scales at baseline, 3, and 6 months. Blood samples will also be taken at baseline and 3 months to measure pro-inflammatory cytokines and acute-phase reactants; neurotrophic factors; and markers of glial dysfunction and astrocyte activation. DISCUSSION:This study is the first clinical trial to examine the efficacy of combined physical and cognitive exercise on cognitive function in older ICU survivors with delirium. The results will provide information about potential synergistic effects of a combined intervention on a range of outcomes and mechanisms of action. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03095417 . Registered on 23 March 2017. Last updated on 15 May 2017.
Project description:BACKGROUND:Previous research suggests that both cognitive training and physical exercise help to maintain brain health and cognitive functions that decline with age. Some studies indicate that combined interventions may produce larger effects than each intervention alone. The aim of this study is to investigate the effects of combined cognitive and physical training compared to cognitive training and physical training alone on executive control and memory functions in healthy older adults. OBJECTIVES:The main objectives of this four-arm randomized controlled trial (RCT) are: to investigate the synergetic effects of a simultaneous, group-based multidomain training program that combines cognitive video-game training with physical exercise, in comparison to those produced by cognitive training combined with physical control activity, physical training combined with cognitive control activity, or a combination of both control activities; to investigate whether event-related potential latencies of the P2 component are shorter and N2 and P3b components assessed in a memory-based task switching task are enhanced after training; and to find out whether possible enhancements persist after a 3-month period without training. METHODS:In this randomized, single-blind, controlled trial, 144 participants will be randomly assigned to one of the four combinations of cognitive training and physical exercise. The cognitive component will be either video-game training (cognitive intervention, CI) or video games not specifically designed to train cognition (cognitive control, CC). The physical exercise component will either emphasize endurance, strength, and music-movement coordination (exercise intervention, EI) or stretching, toning, and relaxation (exercise control, EC). DISCUSSION:This RCT will investigate the short and long-term effects of multidomain training, compared to cognitive training and physical training alone, on executive control and memory functions in healthy older adults, in comparison with the performance of an active control group. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03823183. Registered on 21 January 2019.
Project description:OBJECTIVE:Delirium is common in intensive care patients and is associated with short- and long-term adverse outcomes. We investigated the long-term risk of cognitive impairment and post-traumatic stress disorder (PTSD) in intensive care patients with and without delirium. METHODS:This is a prospective cohort study in ICUs in two Australian university-affiliated hospitals. Patients were eligible if they were older than 18 years, mechanically ventilated for more than 24 h and did not meet exclusion criteria. Delirium was assessed using the Confusion Assessment Method for Intensive Care Unit. Variables assessing cognitive function and PTSD symptoms were collected at ICU discharge, after 6 and 12 months: Mini-Mental State Examination, Telephone Interview for Cognitive Status, Impact of Events Scale-Revised and Informant Questionnaire for Cognitive Decline (caregiver). RESULTS:103 participants were included of which 36% developed delirium in ICU. Patients with delirium were sicker and had longer duration of mechanical ventilation and ICU length of stay. After 12 months, 41/60 (68.3%) evaluable patients were cognitively impaired, with 11.6% representing the presence of symptoms consistent with dementia. When evaluated by the patient's caregiver, the patient's cognitive function was found to be severely impaired in a larger proportion of patients (14/60, 23.3%). Delirium was associated with worse cognitive function at ICU discharge, but not with long-term cognitive function. IES-R scores, measuring PTSD symptoms, were significantly higher in patients who had delirium compared to patients without delirium. In regression analysis, delirium was independently associated with cognitive function at ICU discharge and PTSD symptoms at 12 months. CONCLUSIONS:Intensive care survivors have significant rates of long-term cognitive decline and PTSD symptoms. Delirium in ICU was independently associated with short-term but not long-term cognitive function, and with long-term PTSD symptoms. Trial registration Australian New Zealand Clinical Trials Registry, ACTRN12616001116415, 15/8/2016 retrospectively registered, https://www.anzctr.org.au.
Project description:ICUs are experiencing an epidemic of patients with acute brain dysfunction (delirium) and weakness, both associated with increased mortality and long-term disability. These conditions are commonly acquired in the ICU and are often initiated or exacerbated by sedation and ventilation decisions and management. Despite > 10 years of evidence revealing the hazards of delirium, the quality chasm between current and ideal processes of care continues to exist. Monitoring of delirium and sedation levels remains inconsistent. In addition, sedation, ventilation, and physical therapy practices proven successful at reducing the frequency and severity of adverse outcomes are not routinely practiced. In this article, we advocate for the adoption and implementation of a standard bundle of ICU measures with great potential to reduce the burden of ICU-acquired delirium and weakness. Individual components of this bundle are evidence based and can help standardize communication, improve interdisciplinary care, reduce mortality, and improve cognitive and functional outcomes. We refer to this as the "ABCDE bundle," for awakening and breathing coordination, delirium monitoring, and exercise/early mobility. This evidence-based bundle of practices will build a bridge across the current quality chasm from the "front end" to the "back end" of critical care and toward improved cognitive and functional outcomes for ICU survivors.
Project description:AbstractPrevious research suggests that both cognitive training and physical exercise help to maintain brain health and cognitive functions that decline with age. The main objectives of this four-arms RCT are (1) to investigate the synergetic effects of a group-based multidomain training program that combines cognitive video-game training with physical exercise, in comparison to those produced by cognitive training combined with physical control activity, physical training combined with cognitive control activity, or a combination of both control activities; (2) to investigate in a memory-based task switching task whether event Related Potential (ERP) latencies of the P2 component are shorter, and N2 and P3b components are enhanced after training; and (3) to find out whether possible enhancements persist after a 3-month period without training. One hundred and twenty participants will be randomly assigned to one of the four combinations of cognitive training and physical exercise. The cognitive component will be either video-game training (cognitive intervention, CI) or video games not specifically designed to train cognition (cognitive control, CC). The physical exercise component will either emphasize endurance, strength, and music-movement coordination (exercise intervention, EI) or stretching, toning and relaxation (exercise control, EC). This RCT will investigate the short and long-term effects of combined multi-domain training compared to cognitive training and physical training alone, on executive control and memory functions of healthy older adults, in comparison with the performance of an active control group. This trial is an ongoing project started in 2018. Trial registration: Clinicaltrials.gov ID: NCT03823183; https://register.clinicaltrials.gov/
Project description:Background:Long-term combination of physical exercises has reported benefits for cognitive functions and mood states. However, it remains unclear whether a single bout of combination exercise training has acute positive effects on cognitive functions and mood states in middle-aged and older women. It is important to investigate acute effect of physical exercise because it would help to understand a mechanism of benefits of physical exercise. The purpose of this study was to investigate 30 min of a single bout of combination exercise training on cognition and mood states in middle-aged and older females. Methods:In this single-blinded randomized control trial (RCT), middle-aged and older females were assigned randomly to two groups: a combination exercise group and a no-exercise control group. The former group did the combination exercise training (aerobic, strength, and stretching exercises) for 30 min. Meanwhile, the latter group did not do any exercise and waited for 30 min. We measured cognitive functions and mood performance states before and after the exercise or control interventions. Results:Our main results demonstrated that, compared to the control group, the combination exercise improved inhibition (reverse Stroop and Stroop) and increased vigor-activity mood scores in both middle-aged and older groups. We also found that the only combination exercise group showed the significant positive correlations between improved inhibition performance and improved vigor-activity mood. Discussion:This randomized controlled trial revealed the acute benefits of combination exercise on inhibition in executive functions and vigor-activity in the healthy middle-aged and older females. Our results provided the scientific evidence related to acute effects of the single bout of the combination exercise training. It suggests that we would be better to do the 30 min physical exercise for our health. Clinical Trial Registration:This trial was registered in the University Hospital Medical Information Network Clinical Trials Registry (UMIN000029681). Registered 24 October 2017, https://upload.umin.ac.jp/cgi-bin/ctr/ctr_view_reg.cgi?recptno=R000033922.
Project description:Multidomain lifestyle interventions represents a promising strategy to counteract cognitive decline in older age. Brain-derived neurotrophic factor (BDNF) is essential for experience-dependent plasticity and increases following physical exercise, suggesting that physical exercise may facilitate subsequent learning. In a randomized-controlled trial, healthy older adults (65-75 years) completed a 12-week behavioral intervention that involved either physical exercise immediately before cognitive training (n?=?25; 13 females), physical exercise immediately after cognitive training (n?=?24; 11 females), physical exercise only (n?=?27; 15 females), or cognitive training only (n?=?21; 12 females). We hypothesized that cognition would benefit more from cognitive training when preceded as opposed to followed by physical exercise and that the relationship between exercise-induced increases in peripheral BDNF and cognitive training outcome would be greater when cognitive training is preceded by physical exercise. Greater increases of plasma BDNF were associated with greater cognitive training gains on trained task paradigms, but only when such increases preceded cognitive training (ß?=?0.14, 95% CI [0.04, 0.25]). Average cognitive training outcome did not differ depending on intervention order (ß?=?0.05, 95% CI [-0.10, 0.20]). The study provides the first empirical support for a time-critical but advantageous role for post-exercise increases in peripheral BDNF for learning at an interindividual level in older adults, with implications for future multidomain lifestyle interventions.
Project description:Nonpharmacologic interventions, such as cognitive training or physical exercise, are effective in improving cognitive functions for older adults with mild cognitive impairment (MCI). Some researchers have proposed that combining physical exercise with cognitive training may augment the benefits of cognition. However, strong evidence is lacking regarding whether a combined therapy is superior to a single type of training for older adults with MCI. Moreover, which combination approach - combining physical exercise with cognitive training sequentially or simultaneously - is more advantageous for cognitive improvement is not yet clear. This proposed study is designed to clarify these questions.This study is a single-blinded, multicenter, randomized controlled trial. Eighty individuals with MCI will be recruited and randomly assigned to cognitive training (COG), physical exercise training (PE), sequential training (SEQ), and dual-task training (DUAL) groups. The intervention programs will be 90 min/day, 2-3 days/week, for a total of 36 training sessions. The participants in the SEQ group will first perform 45 min of physical exercise followed by 45 min of cognitive training, whereas those in the DUAL group will perform physical exercise and cognitive training simultaneously. Participants will be assessed at baseline, after the intervention, and at 6-month follow-up. The primary cognitive outcome tests will include the Montreal Cognitive Assessment and the color-naming Stroop test. Other outcomes will include assessments that evaluate the cognitive, physical, and daily functions of older adults with MCI.The results of this proposed study will provide important information regarding the feasibility and intervention effects of combining physical exercise and cognitive training for older individuals with MCI.ClinicalTrials.gov Identifier: NCT02512627 , registered on 20 July 2015.
Project description:Cognitive decline after stroke is highly associated with functional disability. Empirical evidence shows that exercise combined cognitive training may induce neuroplastic changes that modulate cognitive function. However, it is unclear whether hybridized exercise-cognitive training can facilitate cortical activity and physiological outcome measures and further influence on the cognitive function after stroke. This study will investigate the effects of two hybridized exercise-cognitive trainings on brain plasticity, physiological biomarkers and behavioral outcomes in stroke survivors with cognitive decline.This study is a single-blind randomized controlled trial. A target sample size of 75 participants is needed to obtain a statistical power of 95% with a significance level of 5%. Stroke survivors with mild cognitive decline will be stratified by Mini-Mental State Examination scores and then randomized 1:1:1 to sequential exercise-cognitive training, dual-task exercise-cognitive training or control groups. All groups will undergo training 60 min/day, 3 days/week, for a total of 12 weeks. The primary outcome is the resting-state functional connectivity and neural activation in the frontal, parietal and occipital lobes in functional magnetic resonance imaging. Secondary outcomes include physiological biomarkers, cognitive functions, physical function, daily functions and quality of life. This study may differentiate the effects of two hybridized trainings on cognitive function and health-related conditions and detect appropriate neurological and physiological indices to predict training effects. This study capitalizes on the groundwork for a non-pharmacological intervention of cognitive decline after stroke.
Project description:Aerobic exercise and cognitive training have been effective in improving cognitive functions; however, whether the combination of these two can further enhance cognition and clinical outcomes in stroke survivors with cognitive decline remains unknown. This study aimed to determine the treatment effects of a sequential combination of aerobic exercise and cognitive training on cognitive function and clinical outcomes.Stroke survivors (n?=?75) with cognitive decline will be recruited and randomly assigned to cognitive training, aerobic exercise, and sequential combination of aerobic exercise and cognitive training groups. All participants will receive training for 60 minutes per day, 3 days per week for 12 weeks. The aerobic exercise group will receive stationary bicycle training, the cognitive training group will receive cognitive-based training, and the sequential group will first receive 30 minutes of aerobic exercise, followed by 30 minutes of cognitive training. The outcome measures involve cognitive functions, physiological biomarkers, daily function and quality of life, physical functions, and social participation. Participants will be assessed before and immediately after the interventions, and 6 months after the interventions. Repeated measures of analysis of variance will be used to evaluate the changes in outcome measures at the three assessments.This trial aims to explore the benefits of innovative intervention approaches to improve the cognitive function, physiological markers, daily function, and quality of life in stroke survivors with cognitive decline. The findings will provide evidence to advance post-stroke cognitive rehabilitation.ClinicalTrials.gov, NCT02550990 . Registered on 6 September 2015.
Project description:BACKGROUND:Physical exercise, cognitive training, and vitamin D are low cost interventions that have the potential to enhance cognitive function and mobility in older adults, especially in pre-dementia states such as Mild Cognitive Impairment (MCI). Aerobic and progressive resistance exercises have benefits to cognitive performance, though evidence is somewhat inconsistent. We postulate that combined aerobic exercise (AE) and progressive resistance training (RT) (combined exercise) will have a better effect on cognition than a balance and toning control (BAT) intervention in older adults with MCI. We also expect that adding cognitive training and vitamin D supplementation to the combined exercise, as a multimodal intervention, will have synergistic efficacy. METHODS:The SYNERGIC trial (SYNchronizing Exercises, Remedies in GaIt and Cognition) is a multi-site, double-blinded, five-arm, controlled trial that assesses the potential synergic effect of combined AE and RT on cognition and mobility, with and without cognitive training and vitamin D supplementation in older adults with MCI. Two-hundred participants with MCI aged 60 to 85 years old will be randomized to one of five arms, four of which include combined exercise plus combinations of dual-task cognitive training (real vs. sham) and vitamin D supplementation (3?×?10,000 IU/wk. vs. placebo) in a quasi-factorial design, and one arm which receives all control interventions. The primary outcome measure is the ADAS-Cog (13 and plus modalities) measured at baseline and at 6 months of follow-up. Secondary outcomes include neuroimaging, neuro-cognitive performance, gait and mobility performance, and serum biomarkers of inflammation (C reactive protein and interleukin 6), neuroplasticity (brain-derived neurotropic factor), endothelial markers (vascular endothelial growth factor 1), and vitamin D serum levels. DISCUSSION:The SYNERGIC Trial will establish the efficacy and feasibility of a multimodal intervention to improve cognitive performance and mobility outcomes in MCI. These interventions may contribute to new approaches to stabilize and reverse cognitive-mobility decline in older individuals with MCI. TRIAL REGISTRATION:Identifier: NCT02808676. https://www.clinicaltrials.gov/ct2/show/NCT02808676 .