6.4 Cognitive Rehabilitation Strategies

Intervention for treatment of cognitive deficits post traumatic brain injury tend to be diverse with variability between the interventions themselves and the outcome measures used to document results.  For the purposes of this section, interventions were included that either targeted multiple cognitive domains such as attention, memory, information processing speed, executive functions and visuoperceptual function or were non-specific with regards to intended outcome.  For example, a general cognitive rehabilitation program would tend to document outcomes across multiple domains.

What is the evidence for cognitive rehabilitation therapy post ABI?
  1. There is conflicting evidence that a cognitive rehabilitation program focusing on memory strategies and selective attention will have a significant benefit relative to controls.
  2. There is Level 4 evidence that general cognitive rehabilitation therapy post acquired brain injury is effective for improving cognition.  Although there are variable strategies and protocols for cognitive rehabilitation, all comprehensive interventions appear to provide benefit.
  3. There is Level 4 evidence that an outpatient day program is effective for assisting brain injury survivors in returning to competitive employment.

Gordon et al. 60conducted an extensive review of the traumatic brain injury rehabilitation literature and identified 13 studies dealing with rehabilitative treatments of cognitive deficits Gordon et al. 60included studies based on several inclusion criteria: more than 20 participants with TBI and 20 controls, the sample was comprised of more than 75% adults, and more than 75% of the participants were individuals with TBI.  Fourteen studies examining the effects of cognitive rehabilitation strategies are discussed here.  

In a randomized controlled trial by Dirette et al. 61, although there were significant improvements on post intervention results for both intervention and control groups, there was no overall difference between groups when the experimental group was taught to use compensation strategies including verbalization, chunking and pacing.  In this study, the authors did note that control participants spontaneously relied upon compensatory strategies, which may have accounted for improvement. 

Rath et al. 62completed an RCT comparing two cognitive rehabilitation therapies: conventional (cognitive remediation and psychosocial components) versus an innovative rehabilitation approach focusing on emotional self regulation and clear thinking. Outcomes were measured across multiple domains of cognition including attention, memory, reasoning, psychosocial functioning, and problem solving measures.  Significant changes comparing baseline to post intervention outcomes were seen for each group, however, the improvements were different for the interventions.  No between-group comparisons were made.

Neistadt 63divided 45 patients into one of two groups: a remedial group who received individual training with parquetry block assembly, and an adaptive group who received functional skills training over a six-week period. Outcomes for the effect of treatment for constructional test performance revealed that the remedial group improved significantly more than the adaptive group on the Parquetry Block test. However, there were no significant differences on the WAIS-R Block Design subtest after treatment.  Outcomes for the effect of treatment on functional test performance revealed a trend as predicted, although non-significant, toward the functional group improving more than the perceptual skills group. Training-specific learning appears to be an effective approach to rehabilitation as demonstrated by the treatment effect.

Cicerone et al. 64compared an intensive cognitive rehabilitation program to a standard rehabilitation program.  This intensive program included individual and group therapy 4 days per week for 5 hours per day for a total of 16 weeks.  The main outcome for this study was community integration post injury.  The treatment group had a significantly better outcome compared to the control group.  With regards to cognitive outcomes, analysis was not performed on the control group due to incomplete data; however, there was a significant improvement on post intervention composite neuropsychological scores for the treatment group who on average were better at two years post injury than at the start of the intervention.

Harrington and Levandowski 65demonstrated overall cognitive improvement in 18 TBI survivors following a two-year structured cognitive retraining program which consisted of 5 sequential instructional modules focusing on 1) orientation, attention/concentration and psycho-motor skills 2) perceptual cognitive processing 3) perceptual-cognitive integration 4) logical reasoning and problem solving and 5) a transitional community module.  Pre- post comparisons demonstrated significant improvement on all elements of the Luria-Nebraska Neuropsychogical battery except for tactile functioning.

Brett and Laatsch 66studied the effects of a cognitive rehabilitation therapy program for TBI survivors in a high school setting.  The intervention included biweekly 40-minute sessions for a total of 20 weeks.  Cognitive therapy focused on alertness, attention, concentration, perception and memory as well as problem solving.  Only memory demonstrated a statistically significant improvement post intervention whereas general intellectual functioning, concentration and problem solving did not demonstrate significant improvement.

Rattok et al. 67compared three cognitive rehabilitation programs which were similar in intensity, but varied in the emphasis of type of retraining format.  This non-randomized controlled trial addressed cognitive retraining in the domains of attention, personal counseling, individual cognitive remediation and interpersonal communication exercises.  All treatment mixes were equally effective with regards to level of vocational attainment.

Ruff et al. 68in an RCT compared an active treatment based group focusing on attention, spatial integration, memory and problem solving to a control group that focused on computer and video games, coping skills, health, discussion forum, independent living and art.  Both groups improved significantly, however, the treatment group experienced relative gains on memory testing and selective attention, suggesting that focusing on these specific elements has the potential to improve them.

Boman et al. 69in a study of 10 individuals with mild or moderate TBI, after completing 1 hour of an individual cognitive training 3 times a week for 3 weeks, significant improvement was noted on the attention processing training test in sustained attention (p<0.05), selective attention (p<0.05), and alternating attention (p<0.01) pre to post training and at 3 month follow-up.  Scores on the RBMT were also seen to have significantly increased at the 3 month follow-up compared to pre test scores (p<0.05). Changes on the Claeson-Dahl Memory test did not increase pre to post to 3 month follow-up.

Ben-Yishay et al. 70reported a single group intervention of 101 patients with traumatic brain injury who entered into a comprehensive out patient day program consisting of two phases.  At the end of the program, 84% were competitively employable, however over the intervening three years, this declined to only 50% remaining employed. Although no controls are available for this study, there is some evidence to support that a day program is effective for returning brain injury survivors to competitive employment.

Prigatano et al. 71in one of the earlier studies examining neuropsychological functioning found that a out-patient neuropsycholgical rehabilitation program provided significant benefit compared to a control group not receiving further rehabilitation.  This comprehensive, intensive program emphasized increased awareness and acceptance of injury and residual deficits, intensive cognitive retraining and compensatory skills development.  There was improvement in neuropsychological performance in the treatment group compared to the control group.  Emotional distress was noted to substantially decrease in the treatment group.

Salazar et al. 72in a RCT of 120 moderate to severe TBI patients studied the efficacy of an intensive, eight-week, in-patient cognitive rehabilitation program compared to a limited home rehabilitation program with weekly telephone contact from a psychiatric nurse.  Overall there were no differences between groups with regards to return to work or fitness for duty at one-year.  There were also no differences in cognitive, behavioral or quality of life outcomes.  

Cicerone et al. 1had concluded that comprehensive-holistic cognitive rehabilitation should be recommended as a practice guideline for patients with either a stroke or acquired brain injury.  Since completion of this review, further quality studies have been published supporting a general cognitive therapy approach following acquired brain injury.  In the studies by Dirette et al. 61, Rath et al. 62and Cicerone et al. 64comparisons of specific strategies using experimental techniques (randomized and non-randomized) are attempted. All groups demonstrated benefit from the interventions and in the studies by Rath et al. 62and Cicerone et al. 64there were overall trends to improvement for the experimental groups.  The study by Salazar et al. 72provides contradictory results to these other studies in that no benefit was demonstrated for an intensive in-patient rehabilitation program versus a limited home based rehabilitation program.  This study was a RCT and challenges the trend of studies demonstrating the benefit of intensive cognitive rehabilitation programs. 

Although there are differences in the delivery techniques of cognitive rehabilitation therapy, most studies when considering within-group comparisons demonstrated an overall improvement in cognitive abilities across multiple cognitive domains.  The majority of the studies included patients greater than one-year post injury, which would assist in controlling for the effects of spontaneous recovery.  There are limitations in most studies in that typically a time series design is used with pre- and post-intervention testing where the subject acts as their own control. The primary limitation with regards to brain injury rehabilitation is time-dependent confounding.  Two factors contribute to this including anticipated spontaneous recovery as well as the consideration of the practice/ learning effect of repeat neuropsychology testing which may lead to higher scores. 

Analysis of findings from the current review as well as those from Cicerone et al. 2and Gordon 60all suggest that future studies need to control for patient characteristics (e.g., level of impairment needs to be clearly defined, not just severity of injury), spontaneous recovery and practice effects on outcome measures used.  Studies should not just rely on psychometric tests but should consider functional outcome measures and long-term effects of treatment interventions should be monitored through follow-up.

6.4.2 Computer-Assisted Training

What is the evidence for computer assisted cognitive retraining post ABI?

  1. There is Level 2 evidence that computer assisted cognitive retraining is not been an effective adjunct to the rehabilitation program, especially regarding attentional retraining following brain injury.

A specific intervention for improving general cognitive functioning is computer- assisted training.  The use of computer-assisted cognitive retraining has multiple potential benefits within the rehabilitation setting following brain injury.  Computer retraining allows for flexibility in retraining procedures, increased individuality of therapy programs and also decreases the amount of direct time a therapist is with the patient.  It also has the potential of continuing cognitive retraining within the community setting.  Furthermore, as presented at the NIH Consensus Development Panel 73, computer-assisted strategies are used to improve neuropsychological processes, including attention, memory and executive skills. Eight studies were identified that used computer-assisted measures for cognitive rehabilitation following brain injury.

Dou et al. 74in an RCT randomized participants to one of three groups: the computer assisted memory training group (CAMG-treatment - group 1) or the therapist administered memory training group (TAMG-treatment - group 2) with each receiving one month memory training or 3) the control group.  Memory training was similar between the groups but they were delivered differently. The treatment groups received 20 training sessions with each running for 6 days per week and lasting approximately 45 minutes. The control group received no training.  Sessions consisted of: training basic component memory skills in (1) the management of typical daily tasks utilizing/integrating the component memory skills, (2) customized programs and (3) skill consolidation as well as in the generalization of those skills in practice.  Scores on the neurobehavioural cognitive status examination (NCSE) showed significant improvement in the TAMG and CAMG groups (p<0.015, p<0.02 respectively) compared to the control group. Results from the Rivermead behavioural memory test (Cantonese version) showed the CAMG improved significantly compared to the control group (p<0.0001).  Those in the TAMG showed no significant improvement.

Ruff et al. 75evaluated the effect of computer assisted rehabilitation using the THINKable computer program which is a multi-media system that focuses on memory and attention retraining.  Although this study was designed as a randomized controlled cross over design, due to the small number recruited (15), the groups were analyzed together in a pre-post intervention fashion. Psychometric testing revealed modest but significant gains made for some memory and attention measures in each of the groups.

Self practice, presentation of attractive stimuli, multi-sensory feedbacks and personalized training contents were the four different forms of computer-assisted cognitive re-training programmes that Tam and Man 76used to evaluate people with post-head injury amnesia. Participants were randomly assigned to one of four treatment groups (matched diagnostically and demographically): (1) self-paced group, which allowed individuals to move at their own pace in a non-threatening environment; (2) feedback group, which involved immediate provision of feedback in a non-judgmental fashion; (3) personalized group, whereby the computer presented training contents showing the participant’s actual living environment and routines; and (4) the visual presentation group, which was a provision of attractive and bright presentation designed to help individuals engage in the activity. Each group went through one of the four computer-assisted memory re-training strategies.  Results revealed that the patients in the experimental group showed positive improvements on all of the four memory training methods as compared to the control group.  However, there were not statistically significant differences among the four training methods.  Nonetheless, this study showed that computer-assisted memory retraining yield positive results for patients with memory post-head injury amnesia.

Chen et al. 77studied the effect of computer assisted cognitive rehabilitation versus traditional therapy methods.  Within-group comparisons of pre- and post-intervention measures demonstrated significant gains on multiple psychometric tests taking into account multiple statistical comparisons.  However, multivariate analysis comparing the experimental and control groups across the domains of attention, visual-spatial, memory and problem solving did not demonstrate significant differences between the groups.

Gray et al. 78investigated the effects of attentional retraining using a microcomputer-based intervention.  Patients were stratified into closed-head-injury (CHI) or other diagnosis (17 patients diagnosed as CHI) and mild/moderate or severe injury (15 diagnosed as severe) and randomly assigned to receive either attentional retraining or recreational computing (control). Time since injury varied widely from 7 weeks to 10 years.  Immediately following training, the treatment group showed marked improvement on two measures of attention in comparison to the control group, however once premorbid intelligence score and time since injury were included as covariates, this treatment effect was no longer significant.  The experimental group showed continued improvement at 6-month follow-up on tests involving working memory.

Electronic mail (email) may prove useful for reducing the experience of social isolation for patients sustaining acquired cognitive-linguistic impairments.79 Sholberg et al.79were interested in the usability and patient preference of a simplified email interface on eight brain injured patients. Patients were asked to read and reply to four prompt conditions: no prompt, idea prompt, fill-in-the-blank prompt and multiple-choice prompt. Difficulties encountered included computer usability and message composition. Results identified three categories of usability problems: lack of knowledge concerning functionality of keys for word-processing operations, poor conceptual understanding for the mouse operation and poor use of interface prompts. Results also found that there was considerable variation among patient preferences and the types of errors observed in composing emails, and that all patients legitimized the use of email interfaces as a means of reducing social isolation.

6.4.3 Amantadine

What is the evidence for amantadine in improving cognitive functioning post ABI?
  1. There is Level 2 evidence from one RCT that amantadine does not help to improve overall cognitive functioning based on the conclusions of a single RCT.

Amantadine is a non-competitive N-methyl-D-aspartate receptor antagonistand is currently used as an antiviral agent used as a prophylaxis for influenza A, for the treatment of neurological diseases such as Parkinson’s Disease and in the treatment of neuroleptic side-effects such as dystonia, akithesia and neuroleptic malignant syndrome 47. It is also thought to work pre- and post-synaptically by increasing the amount of dopamine 5

Schneider et al. (1999)completed a double-blinded, randomized placebo controlled trial evaluating the effects of amantadine on cognition and behavior. Twenty patients were included in the study and each took amantadine for 2 weeks. Statistical comparison of results evaluating the five subsets of attention, executive/flexibility, memory, behavior and orientation did not demonstrate any significant effect for the use of amanatadine.  


Schneider WN, Drew-Cates J, Wong TM and Dombovy ML. Cognitive and behavioural efficacy of amantadine in acute traumatic brain injury: an initial double-blind placebo-controlled study. Brain Injury, 1999:13(11):863-872.

  • 10 subjects were selected for inclusion in the following randomly controlled cross over study.
  • Subjects were given either amantadine or placebo for 2 weeks, followed by a two week withdrawal period, then amantadine or placebo depending on what they were given first.
  • The Neurobehavioural Rating Scale was completed for all participants.
  • Cognitive improvement was noted over time, but no significant differences were found between the administration of amantadine or placebo.

6.4.4 Cerebrolysin

What is the evidence for cerebrolysin in improving cognitive functioning post ABI?
  1. There is Level 4 evidence that cerebrolysin, a neurotrophic and neuroprotective medication appears to have potential benefit to improve outcome and cognitive functioning post-brain injury.

As explained by Alvarez et al. 80, “Cerebrolysin (EBEWE Pharma, Unterach, Austria) is a peptide preparation obtained by standardized enzymatic breakdown of purified brain proteins, and comprises 25% low-molecular weight peptides and free amino acids.”  Cerebrolysin has been demonstrated to have neuroprotective and neurotrophic effects, and has been linked to increased cognitive performance in an elderly population.

In an open label trial of 20 brain-injured patients, Alvarezet al. 80investigated the potential benefits of using Cerebrolysin which was administered intravenously 20 times over a 4-week period. Although the study included patients with mild, moderate or severe traumatic brain injury based on the Glasgow Coma Scale score, all patients had significant disability ranging from moderate disability to persistent vegetative state on the Glasgow Outcome Scale. The time since injury varied from 23 to 1107 days with 9 cases less than 1 year post injury and 11 cases greater than 1 year post injury. A brief neuropsychological battery (SKT) using 9 tests to specifically evaluate memory and attention demonstrated overall significant improvement for the 9 of 20 patients for whom it could be administered. Glasgow Outcome Scores also significantly improved comparing pre to post intervention scores.