A randomized clinical trial of plasticity-based cognitive training in mild traumatic brain injury.

Clinical practice guidelines support cognitive rehabilitation for people with a history of mild traumatic brain injury (mTBI) and cognitive impairment, but no class I randomized clinical trials have evaluated the efficacy of self-administered computerized cognitive training. The goal of this study was to evaluate the efficacy of a self-administered computerized plasticity-based cognitive training programmes in primarily military/veteran participants with a history of mTBI and cognitive impairment. A multisite randomized double-blind clinical trial of a behavioural intervention with an active control was conducted from September 2013 to February 2017 including assessments at baseline, post-training, and after a 3-month follow-up period. Participants self-administered cognitive training (experimental and active control) programmes at home, remotely supervised by a healthcare coach, with an intended training schedule of 5 days per week, 1 h per day, for 13 weeks. Participants (149 contacted, 83 intent-to-treat) were confirmed to have a history of mTBI (mean of 7.2 years post-injury) through medical history/clinician interview and persistent cognitive impairment through neuropsychological testing and/or quantitative participant reported measure. The experimental intervention was a brain plasticity-based computerized cognitive training programme targeting speed/accuracy of information processing, and the active control was composed of computer games. The primary cognitive function measure was a composite of nine standardized neuropsychological assessments, and the primary directly observed functional measure a timed instrumental activities of daily living assessment. Secondary outcome measures included participant-reported assessments of cognitive and mental health. The treatment group showed an improvement in the composite cognitive measure significantly larger than that of the active control group at both the post-training [+6.9 points, confidence interval (CI) +1.0 to +12.7, P = 0.025, d = 0.555] and the follow-up visit (+7.4 points, CI +0.6 to +14.3, P = 0.039, d = 0.591). Both large and small cognitive function improvements were seen twice as frequently in the treatment group than in the active control group. No significant between-group effects were seen on other measures, including the directly-observed functional and symptom measures. Statistically equivalent improvements in both groups were seen in depressive and cognitive symptoms.

Evaluation of a plasticity-based cognitive training program in schizophrenia: Results from the eCaesar trial.

OBJECTIVE: Cognitive impairment in schizophrenia is a core feature of the disorder. Computerized cognitive training has shown promise in pilot studies. A 26-week randomized blinded placebo-controlled trial was conducted to investigate the effect of a novel computerized cognitive training program on cognitive and functional capacity outcomes. METHOD: The study followed MATRICS guidelines for the evaluation of interventions designed to improve cognitive function in schizophrenia. Participants (N = 150) were randomized to experimental (computerized cognitive training in a game-like format) or active control (computer games) groups. Training was conducted in-clinic, with an intended training schedule of 5 days per week, 1 h per day, for 26 weeks. Co-primary outcome measures were the MATRICS Consensus Cognitive Battery (MCCB) composite score and the UCSD Performance-Based Skills Assessment (UPSA-2) total score, secondary outcome measures included the Cognitive Assessment Interview (CAI) and the Short-Form-12 Mental Composite Score (SF-12 MCS). Target engagement was assessed with task-learning based assessment. RESULTS: At baseline, the groups were well matched. No significant effect of the experimental treatment was seen on the primary or secondary outcome measures compared to the active control. Review of the task learning/target engagement data suggested inadequate target engagement. CONCLUSIONS: Results do not support a cognitive or functional capacity benefit from this implementation of a computerized cognitive training program in people with schizophrenia. In future trials, careful consideration is merited of the assessment of task learning/target engagement, the effects of making the cognitive training game-like on motivation, and the implicit effects of trial requirements on participant selection.

Improvement in memory with plasticity-based adaptive cognitive training: results of the 3-month follow-up.

OBJECTIVES: To investigate maintenance of training effects of a novel brain plasticity-based computerized cognitive training program in older adults after a 3-month no-contact period. DESIGN: Multisite, randomized, controlled, double-blind trial with two treatment groups. SETTING: Communities in northern and southern California and Minnesota. PARTICIPANTS: Four hundred eighty-seven community-dwelling adults aged 65 and older without diagnosis of clinically significant cognitive impairment. INTERVENTION: Random assignment into a broadly available brain plasticity-based computerized cognitive training program experimental group or a novelty- and intensity-matched cognitive stimulation active control. Assessments at baseline, after training, and at 3 months. MEASUREMENTS: The primary outcome was a composite of auditory subtests of the Repeatable Battery for the Assessment of Neuropsychological Status. Secondary measures included trained task performance, standardized neuropsychological assessments of overall memory and attention, and participant-reported outcomes (PROs). RESULTS: A significant difference in improvement from baseline to 3-month follow-up was seen between the experimental training and control groups on the secondary composite of overall memory and attention, (P=.01, d=0.25), the trained processing-speed measure (P<.001, d=0.80), word list total recall (P=.004, d=0.28), letter-number sequencing (P=.003, d=0.29), and the cognitive subscale of PRO (P=.006, d=0.27). Previously significant improvements became nonsignificant at the 3-month follow-up for the primary outcome, two secondary measures of attention and memory, and several PROs. Narrative memory continued to show no advantage for the experimental group. Effect sizes from baseline to follow-up were generally smaller than effect sizes from baseline to posttraining. CONCLUSION: Training effects were maintained but waned over the 3-month no-contact period.

The influence of perceptual training on working memory in older adults.

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.

Cognitive speed of processing training delays driving cessation.

BACKGROUND: As our population ages, interventions that can prolong safe driving for older adults will be increasingly important. METHODS: Data from two studies were combined in order to investigate the effectiveness of cognitive training in delaying driving cessation. Stratified Cox hazard regressions were used to examine risk of driving cessation as a function of training participation, baseline driving, and visual acuity. RESULTS: Older drivers with cognitive speed of processing difficulties who completed speed of processing training were 40% less likely to cease driving over the subsequent 3 years (hazard ratio = 0.596, 95% confidence interval 0.356-0.995, p = .048). Whereas 14% of older drivers who did not receive speed of processing training ceased driving, only 9% of those who completed eight or more sessions of speed of processing training ceased driving. CONCLUSION: Speed of processing training may delay driving cessation among older drivers with speed of processing difficulty.

The ACTIVE cognitive training interventions and the onset of and recovery from suspected clinical depression.

We evaluated the effects of the 3 cognitive interventions fielded in the Advanced Cognitive Training for Independent and Vital Elderly study on 2 subsets of participants-1,606 without and 424 with suspected clinical depression at baseline. In the former group, only the speed of processing (vs. no-contact control) intervention had a significant effect, with its participants being 38% less likely to develop suspected clinical depression at 1 year (adjusted odds ratio = 0.62; p < .01). None of the interventions had a significant effect on recovery from suspected clinical depression in the latter group. Although the etiological mechanism of the speed of processing's protective effect was not isolated, it may result from successful adaptation to age-related changes through selective optimization with compensation.

The ACTIVE cognitive training trial and predicted medical expenditures.

BACKGROUND: Health care expenditures for older adults are disproportionately high and increasing at both the individual and population levels. We evaluated the effects of the three cognitive training interventions (memory, reasoning, or speed of processing) in the ACTIVE study on changes in predicted medical care expenditures. METHODS: ACTIVE was a multisite randomized controlled trial of older adults (>or= 65). Five-year follow-up data were available for 1,804 of the 2,802 participants. Propensity score weighting was used to adjust for potential attrition bias. Changes in predicted annualmedical expenditures were calculated at the first and fifth annual follow-up assessments using a new method for translating functional status scores. Multiple linear regression methods were used in this cost-offset analysis. RESULTS: At one and five years post-training, annual predicted expenditures declinedby $223 (p = .024) and $128 (p = .309), respectively, in the speed of processing treatment group, but there were no statistically significant changes in the memory or reasoning treatment groups compared to the no-contact control group at either period. Statistical adjustment for age, race, education, MMSE scores, ADL and IADL performance scores, EPT scores, chronic condition counts, and the SF-36 PCS and MCS scores at baseline did not alter the one-year ($244; p = .012) or five-year ($143; p = .250) expenditure declines in the speed of processing treatment group. CONCLUSION: The speed of processing intervention significantly reduced subsequent annual predicted medical care expenditures at the one-year post-baseline comparison, but annual savings were no longer statistically significant at the five-year post-baseline comparison.

A cognitive training program based on principles of brain plasticity: results from the Improvement in Memory with Plasticity-based Adaptive Cognitive Training (IMPACT) study.

OBJECTIVES: To investigate the efficacy of a novel brain plasticity-based computerized cognitive training program in older adults and to evaluate the effect on untrained measures of memory and attention and participant-reported outcomes. DESIGN: Multisite randomized controlled double-blind trial with two treatment groups. SETTING: Communities in northern and southern California and Minnesota. PARTICIPANTS: Community-dwelling adults aged 65 and older (N=487) without a diagnosis of clinically significant cognitive impairment. INTERVENTION: Participants were randomized to receive a broadly-available brain plasticity-based computerized cognitive training program (intervention) or a novelty- and intensity-matched general cognitive stimulation program modeling treatment as usual (active control). Duration of training was 1 hour per day, 5 days per week, for 8 weeks, for a total of 40 hours. MEASUREMENTS: The primary outcome was a composite score calculated from six subtests of the Repeatable Battery for the Assessment of Neuropsychological Status that use the auditory modality (RBANS Auditory Memory/Attention). Secondary measures were derived from performance on the experimental program, standardized neuropsychological assessments of memory and attention, and participant-reported outcomes. RESULTS: RBANS Auditory Memory/Attention improvement was significantly greater (P=.02) in the experimental group (3.9 points, 95% confidence interval (CI)=2.7-5.1) than in the control group (1.8 points, 95% CI=0.6-3.0). Multiple secondary measures of memory and attention showed significantly greater improvements in the experimental group (word list total score, word list delayed recall, digits backwards, letter-number sequencing; P<.05), as did the participant-reported outcome measure (P=.001). No advantage for the experimental group was seen in narrative memory. CONCLUSION: The experimental program improved generalized measures of memory and attention more than an active control program.

Brain plasticity and functional losses in the aged: scientific bases for a novel intervention.

Aging is associated with progressive losses in function across multiple systems, including sensation, cognition, memory, motor control, and affect. The traditional view has been that functional decline in aging is unavoidable because it is a direct consequence of brain machinery wearing down over time. In recent years, an alternative perspective has emerged, which elaborates on this traditional view of age-related functional decline. This new viewpoint--based upon decades of research in neuroscience, experimental psychology, and other related fields--argues that as people age, brain plasticity processes with negative consequences begin to dominate brain functioning. Four core factors--reduced schedules of brain activity, noisy processing, weakened neuromodulatory control, and negative learning--interact to create a self-reinforcing downward spiral of degraded brain function in older adults. This downward spiral might begin from reduced brain activity due to behavioral change, from a loss in brain function driven by aging brain machinery, or more likely from both. In aggregate, these interrelated factors promote plastic changes in the brain that result in age-related functional decline. This new viewpoint on the root causes of functional decline immediately suggests a remedial approach. Studies of adult brain plasticity have shown that substantial improvement in function and/or recovery from losses in sensation, cognition, memory, motor control, and affect should be possible, using appropriately designed behavioral training paradigms. Driving brain plasticity with positive outcomes requires engaging older adults in demanding sensory, cognitive, and motor activities on an intensive basis, in a behavioral context designed to re-engage and strengthen the neuromodulatory systems that control learning in adults, with the goal of increasing the fidelity, reliability, and power of cortical representations. Such a training program would serve a substantial unmet need in aging adults. Current treatments directed at age-related functional losses are limited in important ways. Pharmacological therapies can target only a limited number of the many changes believed to underlie functional decline. Behavioral approaches focus on teaching specific strategies to aid higher order cognitive functions, and do not usually aspire to fundamentally change brain function. A brain-plasticity-based training program would potentially be applicable to all aging adults with the promise of improving their operational capabilities. We have constructed such a brain-plasticity-based training program and conducted an initial randomized controlled pilot study to evaluate the feasibility of its use by older adults. A main objective of this initial study was to estimate the effect size on standardized neuropsychological measures of memory. We found that older adults could learn the training program quickly, and could use it entirely unsupervised for the majority of the time required. Pre- and posttesting documented a significant improvement in memory within the training group (effect size 0.41, p<0.0005), with no significant within-group changes in a time-matched computer using active control group, or in a no-contact control group. Thus, a brain-plasticity-based intervention targeting normal age-related cognitive decline may potentially offer benefit to a broad population of older adults.

Memory enhancement in healthy older adults using a brain plasticity-based training program: a randomized, controlled study.

Normal aging is associated with progressive functional losses in perception, cognition, and memory. Although the root causes of age-related cognitive decline are incompletely understood, psychophysical and neuropsychological evidence suggests that a significant contribution stems from poorer signal-to-noise conditions and down-regulated neuromodulatory system function in older brains. Because the brain retains a lifelong capacity for plasticity and adaptive reorganization, dimensions of negative reorganization should be at least partially reversible through the use of an appropriately designed training program. We report here results from such a training program targeting age-related cognitive decline. Data from a randomized, controlled trial using standardized measures of neuropsychological function as outcomes are presented. Significant improvements in assessments directly related to the training tasks and significant generalization of improvements to nonrelated standardized neuropsychological measures of memory (effect size of 0.25) were documented in the group using the training program. Memory enhancement appeared to be sustained after a 3-month no-contact follow-up period. Matched active control and no-contact control groups showed no significant change in memory function after training or at the 3-month follow-up. This study demonstrates that intensive, plasticity-engaging training can result in an enhancement of cognitive function in normal mature adults.