Archives of Physical Medicine and Rehabilitation

journal homepage: www.archives-pmr.org Archives of Physical Medicine and Rehabilitation 2013;94:271-86

REVIEW ARTICLE (META-ANALYSIS)

An Evidence-Based Review of Cognitive Rehabilitation in Medical Conditions Affecting Cognitive Function

Donna M. Langenbahn, PhD,a Teresa Ashman, PhD,a Joshua Cantor, PhD,b Charlotte Trott, PhDc
From aRusk Institute of Rehabilitation Medicine, NYU Langone Medical Center, New York, NY; bMount Sinai School of Medicine, New York, NY; and cJFK-Johnson Rehabilitation Institute, JFK Medical Center, Edison, NJ.

Abstract Objectives: To perform a methodical review of the evidence available for the efcacy of cognitive rehabilitation in individuals with diagnosed medical conditions known to affect cognitive function, and to establish evidence-based recommendations for clinical practice, as appropriate. Data Sources: Ovid Medline and PubMed literature searches were conducted using the terms cognition, cognitive, crossed with the terms rehabilitation, remediation, retraining, training, crossed with 11 medical diagnostic categories. Articles through December 2008 were accessed, with a resulting 2284 abstracts. Study Selection: A total of 211 articles were selected from initial abstract review. These articles were then assessed by committee members, with agreement of at least 2 members, using 9 exclusion and 3 inclusion criteria. A total of 34 remaining articles were submitted to full review. Data Extraction: Articles were reviewed under diagnostic categories using specic criteria recorded on structured data sheets. Classication was performed according to guidelines of the American Academy of Neurology, with agreement between 2 committee members necessary for nal decisions. Data Synthesis: Of the 34 studies fully evaluated, 1 was rated as class I, 6 as class II, 2 as class III, and 25 as class IV. Evidence within each diagnostic area was synthesized for the formulation of Practice Standards, Practice Guidelines, and Practice Options, as possible. Conclusions: Two clinical practice recommendations were advanced, 1 each in the diagnostic areas of brain neoplasms and epilepsy/seizure disorders. Discussion included comments on the research status of the effectiveness of cognitive rehabilitation for cognitive decits related to these medical conditions, as well as suggestions for future directions in research. Archives of Physical Medicine and Rehabilitation 2013;94:271-86 2013 by the American Congress of Rehabilitation Medicine

The efcacy of cognitive rehabilitation (CR) has become a focus of scrutiny in evidence-based reviews (EBRs). In 3 EBRs,1-3 the Cognitive Rehabilitation Task Force (CRTF) of the Brain Injury Interdisciplinary Special Interest Group (BI-ISIG), under the auspices of the American Congress of Rehabilitation Medicine, has developed clinical recommendations for CR interventions for individuals with traumatic brain injury (TBI) or stroke. Several other EBRs on CR effectiveness for individuals with TBI or stroke have been published, all supporting, to a lesser or greater extent, CR efcacy with these populations,4-6 with 3 EBRs7-9 published that support specic CR interventions for children and adolescents

No commercial party having a direct nancial interest in the results of the research supporting this article has or will confer a benet on the authors or on any organization with which the authors are associated.

with acquired brain injury (ABI). Although drawing comparisons to rationales and interventions from studies with adult populations, these last reviewers also consistently cited unique needs and issues in the younger ABI populationdfor example, needs of emphasis on language development, cognitive/academic strategy training, psychosocial/behavioral interventions, and involvement of family/teachers, and issues of possible age-differential effectiveness of CR interventions and growing into decit. In the current EBR, a subgroup of the CRTF examines CR efcacy in individuals with other medical conditions that have primary or secondary effects on brain function (eg, anoxia, encephalitis, brain neoplasm, Parkinsons disease [PD]), who are typically referred for CR. As with TBI and stroke, these cerebral conditions result in reductions in cognitive, perceptual, and behavioral skills that are persistent and prominent in the face of potentially moderate or good medical/neurologic recovery. This

0003-9993/13/$36 - see front matter 2013 by the American Congress of Rehabilitation Medicine http://dx.doi.org/10.1016/j.apmr.2012.09.011

272 review seeks to examine evidence for CR efcacy in individuals with cognitive decits associated with selected medical diagnoses, and to formulate treatment recommendations, as possible, from synthesis of that evidence.

D.M. Langenbahn et al (3) intervention studies involving patients with diagnoses of TBI or stroke; (4) intervention studies involving patients with diagnoses of psychosis, substance use, or dementia; (5) case reports without empirical data; (6) published pilot data later incorporated into larger studies; (7) nonepeer-reviewed articles and book chapters; (8) pharmacologic-only interventions; and (9) noneEnglish-language articles. Additional criteria for inclusion in the review were that authors (1) stated some form of cognitive improvement as a treatment goal, and (2) assessed cognitive processes as primary or secondary outcome measures. At this stage, 2 articles were also excluded because of participants not tting medical diagnostic criteria (table 1 shows totals at each stage). The remaining 34 articles, in 8 diagnostic categories, were rated using American Academy of Neurology classications for therapeutic studies (table 2).14 This classication system results in relatively rigorous standards for treatment recommendations, as class IV evidence is not considered in examining the strength of evidence. Of the 4 committee members, all practitioners and researchers of CR except 1 had participated in previous EBRs. To train the new reviewer adequately, as well as ensure reliability and an understanding of the methodology and form used for article rating, each committee member rated the same 4 initial articles and participated in a group discussion of these ratings before starting the nal review. The remaining 30 articles were randomly assigned to 2 of the 4 committee members. Final classication required agreement by 2 committee members, with disagreements rst addressed by discussion, and, if necessary, by then obtaining a third review. After classication was completed, overall evidence was examined, and recommendations were derived from consideration of relative evidence strength. We used terminology and denitions adopted from Cicerone et al1 in advancing practice parameters, with Practice Standards, Practice Guidelines, and Practice Options representing descending levels of strength (table 3).

Methods
The following diagnostic groups were considered for review based on consensus by subcommittee members that the condition could have direct or indirect impact on cognitive functioning: anoxia/hypoxia, encephalitis, epilepsy, human immunodeciency viruseacquired immunodeciency syndrome encephalopathy, Huntington disease (HD), systemic lupus erythematosus (SLE), Lyme disease and other tick-borne encephalopathy, neoplasms, PD, and metabolic encephalopathy. Multiple sclerosis was omitted as a diagnostic group because of recent publication of 2 comprehensive reviews10,11 of CR effectiveness, 1 in a Cochrane review. Similarly, the effectiveness of CR in treating mild cognitive impairment and early-stage Alzheimer disease has been examined in recent reviews12,13 and was not considered. Ovid Medline and PubMed literature searches were conducted for articles published through the end of 2008 using the following search word combinations: cognition, cognitive, crossed with the terms rehabilitation, remediation, retraining, training, in turn, crossed with the above diagnostic categories. The broad category of neoplasms yielded cognitive intervention studies involving tumors of the brain, but none on possible effects of chemotherapy treatments for other cancers. The diagnostic category was thereafter limited to brain neoplasms. An article on toxic encephalopathy was found in searching encephalitis, but a subsequent search using toxic encephalopathy yielded no additional results. Reference lists of chosen articles were also checked for relevant articles, and Cochrane databases were reviewed. The initial search yielded 2284 abstracts across 11 diagnostic groups. Abstracts were reviewed by at least 2 committee members and selected if 1 member believed that the abstract might represent a CR article in a targeted diagnostic group. This step yielded 211 articles to be scanned, with the following publication types excluded: (1) review articles and nonintervention theoretic articles; (2) treatment reports without adequate intervention specication;

Results
Of 34 studies fully evaluated, 1 was rated as class I, 6 as class II, 2 as class III, and 25 as class IV (table 4). Results and recommendations are presented by diagnostic area. An overview of salient medical issues, typical impacted brain areas, and known cognitive effects are also presented for each diagnosis. Class I, II, or III studies are given priority, with class IV studies being summarized only briey, except where clinical issues are deemed important to highlight. Each section ends with a summary and recommendations statement.

List of abbreviations:
ABA design 3-phase single-subject research design consisting of no-intervention baseline (A), intervention (B), and intervention withdrawal (A) ABI acquired brain injury APT Attention Process Training BI-ISIG Brain Injury Interdisciplinary Special Interest Group CM compensation method CNS central nervous system COPD chronic obstructive pulmonary disease CR cognitive rehabilitation CRP cognitive remediation program CRTF Cognitive Rehabilitation Task Force EBR evidence-based review HD Huntington disease PD Parkinsons disease PT physical therapy QOL quality of life RCT randomized controlled trial RM retraining method SLE systemic lupus erythematosus TBI traumatic brain injury

Brain neoplasms
Neoplasms are tissue masses resulting from abnormal growth and proliferation of cells. These tissue masses, often forming tumors, may be either benign or malignant, and may recur after attempts at removal or eradication. Specic attribution of causality for cognitive decits from brain neoplasms is difcult since treatment may include excision, radiation, and/or chemotherapy, any of which may also affect cognition. Overall, associated cognitive difculties tend to be in areas of attention, memory, and executive functioning.15 We classied 11 articles on CR for treating the cognitive effects of brain neoplasms, 3 as class II studies and 8 as class IV. Butler et al16,17 conducted 2 class II studies, an initial pilot study www.archives-pmr.org

Cognitive rehabilitation in medical conditions

Table 1 Total items evaluated in each phase of review

273 statistically signicant between-group improvement in measures of academic achievement and parental ratings of attention. The treatment group showed signicant increases in the use of metacognitive strategies. There were trends in improved neuropsychological functioning, but no signicant between-group differences. Poppelreuter et al19 conducted an RCT examining specic rehabilitation strategy training in 157 adult inpatients with hematopoietic stem cell transplantation in the third class II study. Participants were randomly assigned to treatment groups consisting of neuropsychological training and individualized computer-supported training. A no-training control group was recruited separately over a 3-month period. Neuropsychological training focused on improving attention and everyday memory, as well as practice using compensation strategies and techniques to improve attention and memory skills. In the second training group, participants engaged in computerized tasks addressing attention and memory, with individual coaching for specic impairments. All 3 groups showed signicantly improved performance on neuropsychological outcome measures, with no signicant between-group differences. There were no signicant differences in correlations between neuropsychological performance and selfreport questionnaires measuring perceived everyday cognitive performance. Eight class IV studies all reported positive results from CR in individuals with brain tumors; 4 were case series, and 4 were case studies. In 1 case series, Barakat et al20 treated 13 children with brain tumors, ages 8 to 14 years, and their parents. Treatment involved group social skills training, emphasizing guided roleplay and corrective feedback. The authors found positive changes on measures of social skills and social competence, with both parents and children reporting high satisfaction with the intervention. Sherer et al21 conducted a retrospective study of CR in 13 adults with surgical resection of primary malignant brain tumors, an average of 6 years postsurgery. Patients received 3 weeks to 41/2 months of CR training, comprising 5 hours of daily individual and group treatment and focused on learning compensatory use of a daily organizer and functional strategies. Six participants showed signicant increases in independence as judged by clinician ratings, with treatment gains being maintained at 8-month follow-up. In a feasibility study, Locke et al22 reported on dyads of adult patients with brain tumors and their caregivers who engaged in a 2-week problem-solving and memory book intervention modeled on that used by Sohlberg and Mateer.23 Assessment of 13 dyads completing treatment indicated that 88% of patients were using study-specic strategies at posttesting, with 50% reporting use at 3-month follow-up. In a case series of 23 adult patients with low-grade left hemisphere glioma, Teixidor et al24 selected 8 patients who received 1 hour of speech therapy weekly for 3 weeks, using auditory and visual exercises to

Total Total Articles Abstracts Articles in Full Article Diagnostic Category Reviewed Scanned Review Classication I II III IV Anoxia Encephalitis Epilepsy HIV/AIDS HD SLE Lyme disease and TBE Metabolic encephalopathy Neoplasms (brain) PD Toxic encephalopathy Totals 92 68 360 322 49 15 5 110 805* 232 226 2284 22 19 36 12 3 2 0 13 48 24 32 211 3 8 5 0 1 1 0 0 11 4 1 34 3 1 1 1 6 8 2 1 1 1 2 8 3 1 1

25

Abbreviations: AIDS, acquired immunodeciency syndrome; HIV, human immunodeciency virus; TBE, tick-borne encephalopathy. * Category included all neoplasms in original abstract search.

and a follow-up multicenter randomized controlled trial (RCT), with child and adolescent survivors of central nervous system (CNS) tumor treatment (ie, resection, cranial radiation, and/or chemotherapy). In each study, they assessed the efcacy of an integrative cognitive remediation program (CRP) combining components of Sohlberg and Mateers18 Attention Process Training (APT) with hierarchically graded massed practice, strategy acquisition, and cognitive behavioral therapy. The authors hypothesized that CRP would result in improved academic achievement and cognitive functioning in participants. In the rst study,16 with 31 participants between 6 and 22 years of age, 21 cancer survivors received CRP and 10 were in a waitlist control group. Testing with measures of simple and vigilance attention indicated signicant improvement in the CRP group after treatment, whereas the control group showed no improvement. Neither group showed gains on a test of arithmetic achievement. In the larger study,17 two thirds of the 161 participants were randomly assigned to CRP and one third to a waitlist control. CRP participants were seen for up to 20 two-hour weekly sessions for 4 to 5 months. Blinded outcome indices of academic achievement, brief focused attention, working memory, memory recall, and vigilance were assessed at baseline, 6 weeks, 4 months, and 6 months after enrollment, but treatment providers were not blind to randomization. Participants who received CRP showed

Table 2

Denition of classication of evidence for intervention studies14

Class I: Prospective, randomized controlled clinical trial with masked outcome assessment in a representative population. The primary outcome, inclusion criteria, and exclusion criteria must be clearly dened. Dropouts and crossover to the other group are minimal. Baseline characteristics must be similar between groups. Class II: Prospective matched group cohort study in a representative population with masked outcome or a randomized controlled trial that has 1 signicant aw (eg, primary outcome not clearly dened). Class III: All other controlled trials (including well-dened natural history controls or patients serving as own controls) in a representative population where outcome is independently assessed or independently derived by objective outcome measurement. Class IV: Evidence from uncontrolled studies, case series, case reports, or expert opinion.

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Table 3 Denition of levels of recommendations2,3

D.M. Langenbahn et al

Practice Standards

Practice Guidelines

Practice Options

Based on at least 1 well-designed class I study with an adequate sample, with support from class II or class III evidence that directly addresses the effectiveness of the treatment in question, providing substantive evidence of effectiveness to support a recommendation that the treatment be specically considered for people with acquired neurocognitive impairments and disability. Based on 1 or more class I studies with methodologic limitations, or well-designed class II studies with adequate samples, that directly address the effectiveness of the treatment in question, providing evidence of probable effectiveness to support a recommendation that the treatment be specically considered for people with acquired neurocognitive impairments and disability. Based on class II or class III studies that directly address the effectiveness of the treatment in question, providing evidence of possible effectiveness to support a recommendation that the treatment be specically considered for people with acquired neurocognitive impairments and disability.

improve verbal working memory. Five recovered to preoperative levels at 3-month posttesting, with 3 showing signicant improvements from postoperative decline. In the rst of 4 class IV case studies, Butler25 used modied APT,18 with increasing demands to include real-world (homework) tasks, to treat a 10-year-old boy with a brain tumor who had undergone cranial irradiation. The child showed signicant improvements in attention and arithmetic skills after a 6-month treatment period. Duval et al26 treated a 23-year-old man after surgical removal of a left temporal ganglioglioma, with treatment focused on improving working memory via acquisition of 3 organizational strategies. The patient showed improved working memory, generalized strategy use in everyday life, and stable effects at 3-month follow-up. Kerns and Thomson27 designed a compensatory memory system for a 13-year-old girl with signicant memory decline and falling grades after irradiation of an intracranial astrocytoma. Follow-up neuropsychological data did not indicate signicant improvement, but after 2 years she continued to use her memory notebook and to arrive at class and complete assignments on time. Rao and Bieliauskas28 treated a 45-year-old man in a 4-month program of strategy use, selfmonitoring, self-cuing, and family therapy to address chronic impairments after right temporal lobe astrocytoma resection, with resulting improvements in neuropsychological data and work efciency. Summary and recommendations Previous reviews on the effectiveness of CR in children and adolescents with ABI posited either a Practice Guideline8,9 or Practice Option7 for treating decits in attention or memory, or both. Our review supports advancement of a Practice Guideline, with results of 2 class II studies16,17 totaling 192 subjects supporting the use of process-based CR interventions (eg, APT, strategy acquisition and internalization, self-monitoring, and corrective feedback) as probably effective in treating attention and memory decits in children and adolescents who undergo resection, radiation, or both after diagnosis of brain neoplasm. Evidence for effectiveness of these approaches in adults with brain neoplasms is equivocal, thus preventing a recommendation to be made for adults in this population.

Epilepsy/seizure disorders
Epilepsy comprises a set of disorders with divergent symptoms, all involving episodic abnormal electrical brain activity. Epilepsy is associated with genetic, congenital, and developmental conditions

in individuals younger than 40 years, and with ABI and CNS infections at any age. Different epilepsy types and foci may differentially affect brain and cognitive function, as may the frequency, intensity, and chronicity of seizures. The number and the dosage of antiepileptic drugs also affect cognition. There were 5 articles involving individuals with epilepsy in the nal review: 1 class II study, 1 class III study, and 3 class IV studies. In the class II study, an RCTwith no mention of masking techniques, 44 outpatient adults with focal seizures and attention impairments receiving carbamazepine monotherapy participated in 1 of 3 treatment conditions: the retraining method (RM), the compensation method (CM), or a waitlist control.29 Training consisted of 6 weekly, individual, 1-hour sessions aimed at improving divided attention. In the RM condition, participants rehearsed responses, with task difculty automatically increasing with improved performance. In the CM condition, patients were made aware of their everyday attention and memory failures, and subsequently taught to compensate for these with daily homework and follow-up discussion aimed at internalization of strategy use. Outcome measurement was in 4 areas: training-related neuropsychological tests, general neuropsychological tests, and self-report of both functioning and quality of life (QOL). Both treatment groups showed improvements in neuropsychological tests related to training, with RM subjects showing increased response rates and CM subjects remembering more words. Compared with the waitlist control group, both RM and CM groups had fewer cognitive complaints and increased QOL scores at posttreatment and 6-month follow-up assessments. In a class III comparison group study of 112 adult patients with medication-resistant focal epilepsies who had undergone temporal lobe surgery, approximately half received acute rehabilitation therapy, while the other group received no rehabilitation.30 Patient groups were recruited at 2 separate rehabilitation centers, but did not differ in age, age at seizure onset, handedness, type/side of surgery, successful outcome of surgery, or intelligence quotient. The no-treatment group scored signicantly lower at pretest on measures of verbal learning. CR consisted of ve 1-hour sessions of metacognitive group therapy weekly, and 4 to 5 sessions of computer-based exercises in attention, memory, and executive functioning. Occupational therapy also focused on teaching functional strategy use. Results of attention and memory testing indicated a signicant difference between groups on measures of verbal learning and memory, which remained stable or improved in the treatment group but declined in the no-treatment group. In a class IV single case study, a 32-year-old man with idiopathic epilepsy showed improved scores on tests of immediate and delayed memory after a 6-week program to treat decits in

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Table 4 Authors

Evidence table Class Study Design II Small-group RCT comparison pilot study with pre- and posttesting Subject(s) 31 children and adolescents at least 1 year posttreatment of CNS cancer Treatment Narrative Outcome Measures Findings

Brain Neoplasms Butler and Copeland16

Butler et al17

II

Compared 6 months (w50 sessions) of training with APT, strategy use, and cognitive behavioral therapy (nZ21) with waitlist control (nZ10) Multicenter RCT with pre- and 161 children and adolescents Compared 4 to 5 months (up posttesting at least 1 year to 20 sessions) of training posttreatment of CNS with APT, strategy use, and cancer cognitive behavioral therapy (nZ108) with waitlist control (nZ53)

 Academic tests Signicant differential  Continuous Performance Test improvement in CR group in all Digit span measures (except academic),  Sentence memory with largest effect size in

Continuous Performance Test

 Academic tests  Continuous Performance Test-II  Digit span  Sentence memory  Rey Complex Figure  Rey Auditory Verbal Learning Test  Stroop  Attention ratings  Self-esteem ratings  Test for Attention Performance  Questionnaires of activities of daily living, QOL, cognition, and emotion  Social skills  QOL  Wechsler Intelligence Scale for Children-III  Program rating  Clinician ratings of independence and productivity

Signicant differential improvement in CR group in academic measures, as well as in parental report on ratings of attention.

Poppelreuter et al19

II

RCT with 3 comparison groups, pre- and posttesting

Barakat et al20

IV

Case series pilot study with pretesting and posttesting 9 months later

Sherer et al21

IV

Case series with pre- and posttesting

157 individuals with stem cell Compared 4-weekly group transplantation during 3training in attention and to 5-week inpatient stay memory with computerized attention/memory training and no-treatment control 13 children (ages 8e14) at Compared training in 3 social least 6 months skills groups for both posttreatment for brain children and parents tumors and their parents meeting weekly for 6 sessions 13 patients with malignant 5-h/d outpatient treatment tumor resection in functional skills, use of memory aids, brain injury education, and counseling 13 pairs of patients with brain tumors and caregivers 2-week daily training in memory notebook use and problem solving, compared with no-treatment control group

All 3 groups showed improvement posttreatment, with no differential effects evident.

Improvement reported on measures of social skills and social competence.

Locke et al22

IV

Feasibility study and pilot small-group comparison study with pre- and posttesting

 Compensation Questionnaire  End-of-study feedback  Functional Assessment of Cancer TherapyeBrain  Mayo-Portland Adaptability Inventory, 4th revision

At follow-up, 7 patients had increased independence, 4 were unchanged, 1 had decreased independence, and 1 had died. At 3-month follow-up, 50% of treated patients used trained techniques, 88% satised with intervention. Change measures showed no differences between groups. (continued on next page)

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Table 4 (continued ) Authors Teixidor et al24 Class Study Design IV Case series with pre- and posttesting Subject(s) 23 patients with resection of low-grade glioma in language areas Treatment Narrative Outcome Measures Findings 3 weeks of speech therapy, 1  8 selected tests from the Boston Diagnostic Aphasia hour weekly using auditory Evaluation and visual exercises to improve verbal working memory 6-month training with modied APT, arithmetic skill acquisition, strategy learning, and cognitive behavioral therapy. 6-month (4/wk) strategy use training in 3 areas of working memory: processing load, updating, and dual-task monitoring; strategy application to real-life scenarios Training in use of memory notebook, adapted for an academic setting 4-month once-weekly training in tasks of attention, visual scanning, processing speed; onceweekly marital psychoeducation sessions Compared retraining with repetition and rehearsal, training in compensatory strategy use, and notreatment condition for decits in attention and memory

Butler25

IV

Single case study with preand posttesting

10-year-old boy with brain tumor and cranial irradiation

Duval et al26

IV

Single case study with 23-year-old man 9 months multiple baseline measures after surgical resection of at pre-, intermediate, post-, ganglioglioma and 3-month testing points

All 8 patients examined who had had postoperative declines in verbal working memory showed improvement, with 5 recovering to preoperative levels.  Continuous Performance Test Continuous Performance Test  Grade level in arithmetic results improved from markedskills moderate impairment to within normal limits; arithmetic skills improved 1.5 to 2.0 grade levels.  Measures of attention, Improvements were noted on executive function cognitive measures, self Self-ratings of attention and ratings, and responses to memory scenarios; generalization to  Verbal responses to real-life performance in real-life scenarios scenarios was observed. Results  Performance in real-life were maintained at 3 months. scenarios
 Tests of intelligence and memory  Use of memory notebook  Use of daily checklist

Kerns and Thomson27

IV

Single case study with preand posttesting

Rao and Bieliauskas28

IV

Single case study with preand posttesting

13-year-old girl with severe memory decit postirradiation of intracranial tumor 45-year-old man status post right temporal lobotomy for tumor removal

Data showed consistent use of memory notebook and daily checklist more than 18 months postinitiation of training.  Tests of intelligence, Signicant improvement in tests attention, memory, visual of visual attention, scanning, visuospatial skills, visuospatial ability, processing and motor speed speed; improvement noted in  Self-report and signicant self-report and signicant other report other report.
 Training-related neuro psychological tests  Nonetraining-related neuropsychological tests  Neuropsychological self-report  QOL self-report

Epilepsy/Seizure Disorders II Engelberts et al29

RCT comparing 2 training conditions and waitlist control with pre-, post-, and 6-month follow-up testing

44 patients with focal seizures and attention decits

Both treatment groups showed improvement in trainingspecic test and had fewer cognitive complaints and an increase in QOL report at posttest and 6-month follow-up. (continued on next page)

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Table 4 (continued ) Authors Helmstaedter et al

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Class Study Design III

Subject(s)

Treatment Narrative

Outcome Measures
 Verbal memory  Figural memory  Psychomotor speed and attention

Findings

Case series with matched 112 patients status post patients from 2 different temporal lobe surgery (57 sites (patients at 1 site had left side, 55 right side) treatment), with pre- and posttesting

Gupta and Naorem31

IV

Single case study with multiple baseline assessments performed both pre- and postintervention Single case study with preand posttesting

Training in use of For individuals with right-sided compensatory strategies; surgery, the CR training effect exercises in attention, was signicant for verbal problem solving, and memory, with nontreated memory; practical work-life patients being 4 times more exercises; individual likely to show a decline in counseling; and social/ scores than treated patients. physical activities 32-year-old man 8 years after 6-week once-weekly training  Neuropsychological measures Improvement noted in primarily of attention, seizure onset with in visual scanning and neuropsychological measures, memory attention and memory memory strategy use, with with concomitant improvement  Memory checklist decits supportive therapy noted in emotional state. 37-year-old woman 9 months 3 months of weekly treatment after clipping of right consisting of CR and internal carotid artery psychotherapy aneurysm, with nonepileptic seizures 7-year-old boy with intractable seizures Combined cognitive and anxiety-reducing techniques to optimize learning capability during preseizure and seizure cycles Compared 53 subjects receiving CR intended to stimulate attention, learning, and logicaldeductive thinking added to standardized multidimensional care, with 52 subjects receiving latter program only Six-month operant conditioning program to train bowel/bladder continence, daily activity level, nonaggressive behavior

Laatsch and Taber32

IV

Humphries et al33

IV

Single case study with preand posttreatment assessment

 Observational ratings of emotional state  Wechsler Adult Intelligence Patient had cessation of seizure ScaleeRevised activity, with substantial  Wechsler Memory improvement in memory scores. ScaleeRevised  Trailmaking Test  Stroop  Wisconsin Card Sorting Test  Measurement of time 20% increase in time spent actively spent in class actively engaged in class instruction instruction after intervention.

Anoxia or Hypoxia Incalzi et al34

RCT with 2 treatment groups 105 COPD patients with with baseline, 1.5-, 4-, 6hypoxemia evident at rest month blinded assessments (nZ36) or with effort (nZ69)

 Mini-Mental State Examination  Mental Deterioration Battery

No signicant improvement in either group; no signicant effect of CR intervention. Trend toward improvement in both groups in verbal uency and verbal memory.

Goldberg and Ellis35

IV

Single-subject AB design with 31-year-old man with anoxic pretreatment baseline, encephalopathy after posttest, and 4-month cardiac arrest assessments

Operationalized counts:
    Initiation of toileting Physical activity Mental activity Aggression

At 4-month follow-up, patient showed improvement in all target behaviors.

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Table 4 (continued ) Authors McLean et al36 Class Study Design IV Subject(s) Treatment Narrative Using self-instruction model, trained 1 subject in a study skill method and the other in orientation. CR was combined with use of physostigmine. Outcome Measures
 Correct/incorrect details recall  Wechsler Memory Scale eLogical Memory and Visual Reproduction  Selective Reminding Test  Test of orientation  Count of autobiographical events recalled

Findings Increase noted during training phase in correct details, with decrease in incorrect details. Improvement in neuropsychological measures was also noted during training phase. Patient able to recall 80% of events with technique; retention maintained 11 months later compared with 49% recall using written diary review Improvement noted on posttesting, particularly on tests of executive function, with improvement maintained at 4- and 8-month follow-up.

Two single case studies with 22- and 38-year-old men; ABA design; graphic results anoxia from carbon presentation monoxide poisoning

Encephalitis Berry et al37

IV

Case study with 3 conditions: 63-year-old woman 3 years SenseCam, written diary, after limbic encephalitis and return to baseline measures

Use of SenseCam for recording/reviewing daily events with spouse

Del Grosso Destreri et al38

IV

Case study with pre-, post-, 4-month follow-up, and 8month follow-up testing

53-year-old woman 1 month after herpes simplex encephalitis

Dewar and Wilson39

IV

Case study with pretesting 7 weeks postonset and posttesting 8 weeks later

2 weeks daily inpatient sessions, then 2/wk outpatient sessions; trained use of memory notebook, attention, visuospatial abilities, planning, and memory strategies 24-year-old woman 2 months 8 outpatient sessions aimed after encephalitis lethargic at awareness, management of memory, and learning problem-solving skills

 Comprehensive neuro psychological testing

Emslie et al40

IV

Single-case design (ABA) with nZ4; odds ratio test to examine changes in target behaviors Case study with 10-day baseline and posttesting

Miotto41

IV

3 men and 1 woman Trained subjects and their postencephalitis with age caregivers in use of paging range 30 to 49 years; time system for management of since onset 6 months to 20 problems in memory and pager, with success rates years planning ranging from 45% to 96%.  Standardized tests of naming Signicant improvement on 66-year-old woman 144-week training in use of  Recall for names of people months postillness from mnemonic strategies standardized tests of naming, and objects viral meningoencephalitis (verbal and visual) to observed and reported  Daily recording in patients overcome naming decit improvement in retrieval of log names of people and objects in everyday life.

 Wechsler Adult Intelligence Signicant improvement in scaled Scale-III scores on all intellectual  Wechsler Memory Scale-III measures and most memory and  Delis-Kaplan Executive Func executive function measures; tioning Systeme Inhibition, patient returned to previous Category Fluency, Phonemic work. Fluency  List of possible actions and All 4 subjects were signicantly messages generated for each more successful in memory and subject planning during time using

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Table 4 (continued ) Authors Miotto

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Class Study Design IV Case study with pre- and posttesting

Subject(s) 44-year-old man 9 months postillness from herpes simplex encephalitis

Treatment Narrative

Outcome Measures
 Comprehensive neuro psychological test battery  Recall for names and information read in newspaper paragraph

Findings No change on cognitive tests, but improved recall on tested names and paragraph information, with reported improved recall in everyday life. Improvement on tests of visuospatial skills, visuomotor speed, and memory, and executive function; tests of evoked potentials indicating some increase in cognitive efciency; return to work Both verbal mediation and learning of action sequence peaked at 10 weeks of training, with action sequence being maintained at both 14-week and 3-month observations. Treatment group receiving CR performed better than control group on executive functioning tasks requiring rule shift and organization skills.

Greve et al43

IV

Case study with pretesting at 44-year-old woman 6 weeks 6 weeks postonset and postillness from St. Louis posttesting after 1 year encephalitis

6-month errorless learning training in use of mnemonic strategies (motor and visual) to remember names of people and retain new information  Comprehensive neuro 3 months of outpatient CR psychological test battery with education and  Psychophysiologic recording hierarchical approach to training skills in attention, working memory, processing speed
 Tests of intelligence, attention, and memory  Graphic presentation of verbal mediation and performance of discrete and sequenced actions  Tests of working memory, attention, processing speed, and executive function  Cognitive Estimation Test  Self-rated mood

Giles and Morgan44

IV

Case study with pre- and posttesting of cognitive abilities and baseline, posttesting, and 3-month follow-up assessment of functional skills RCT with 2 treatment groups and pre- and posttesting

29-year-old man 5 years after 14-week behavioral program herpes simplex using positive encephalitis reinforcement to chain 9step sequence of actions with verbal memory links

Parkinsons Disease Sammer et al46

II

Tamir et al47

III

26 inpatients with idiopathic Compared ten 30-minute PD treated during a 3- to 4sessions of CR to train week hospital stay executive functioning on sets of working memory tasks (nZ12) with standard treatment (nZ14) RCT with patients in 2 23 outpatients with Compared 6 weeks (12 stratied treatment groups idiopathic PD from stages sessions) of 1-hour added with pre- and posttesting 1.5 to 3 and no indications training in mental imagery of dementia and relaxation (nZ12) with program of physical exercise only (nZ13)

 Functional tests of motor Signicant improvement in sequences and balance performance of motor  Mental, motor, and activities sequences in treatment group, of daily living ratings signicant increase in mental  Cognitive tests of ability ratings; nonsignicant visuospatial ability and to marginal improvement on attention

cognitive tests.

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Table 4 (continued ) Authors Kamsma et al48 Class Study Design IV Case series with pre- and postassessment via video recording; 3 patients assessed after 1 year Subject(s) 10 outpatients with PD from stages 2 to 4 and no indications of dementia Treatment Narrative Six 1-hour training sessions consisting of mental practice of motor sequences integrated with physical practice; internalization of mental practice trained via use of self-instruction 6 weeks, 12 sessions each of 1 hour of computerized cognitive training in attention, abstract reasoning, and visuospatial abilities and 1 hour of motor training Group intervention of 8 sessions teaching cognitive-behavioral coping and 8 sessions of cognitive strategy training targeting memory compensation Outcome Measures Ratings of video recordings to assess:
 Learning of strategies  Executional, sequential, and intentional errors  Quality of initial and nal body position  Tests of mental status, attention, word uency, verbal memory, and visual reasoning

Findings Patients in PD stages 2 and 3 achieved perfect learning of strategies to execute 2 motor sequences, with patients in stage 4 showing improvement; 3 patients showed retention of learning after 1 year. Patients showed signicant improvements in verbal uency, verbal memory, and visual reasoning at posttest that were maintained at 6month follow-up.

Sinforiani et al49

IV

Case series with pre-, post-, and 6-month follow-up testing

20 outpatients with earlystage PD and mild cognitive symptoms

Toxic Encephalopathy II van Hout et al50

RCT with 2 treatment groups 95 patients with chronic (each receiving both solvent-induced treatments in crossover encephalopathy design) and waitlist control; pre-, post-, and 3month follow-up testing

 Tests of memory, learning, and speed  Self-reported memory complaints  Sickness Impact Prole  Target Complaint List  Tests of acceptance, coping, and mood  Treatment satisfaction and perceived change

Only the treatment group improved on objective memory tests and symptom complaints; treatment effects diminished at follow-up assessment.

Huntington Disease Zinzi et al51

IV

Pilot case series study with repeated testing

 Mini-Mental State 40 individuals with early- and Training 3 per year in 3Examination middle-stage HD treated week inpatient program to  Zung Depression Scale during inpatient improve attention,  Barthel Index rehabilitation stay over memory, and language course of 3 years skills; treatment embedded in multidisciplinary rehabilitation

Patients showed maintenance of baseline level of cognitive function over the 3-year treatment course.

Systemic Lupus Erythematosus IV Pilot case series study with Harrison et al54 pre- and posttesting

17 subjects with diagnosed SLE

Group intervention of 8 weekly 2-hour sessions of functional strategy training and psychosocial support

 California Verbal Learning Test  Cognitive Symptoms Inventory  Questionnaires of memory and metamemory function  Beck Depression Inventory

After treatment, patients reported greater use of strategies, memory capacity, and efcacy; they reported a reduction in cognitive and depressive symptoms, and showed improved list learning.

D.M. Langenbahn et al

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Cognitive rehabilitation in medical conditions attention and memory.31 In another case study, a 37-year-old woman with diagnosed pseudoseizures showed improvements on measures of intelligence, memory, and executive functioning after 3 months of weekly individual treatment including both CR and supportive psychotherapy.32 Both studies emphasized use of techniques to focus attention, as well as training in strategies for memory storage and retrieval. Another class IV study33 described dynamic assessment in the analysis of a 7-year-old boy with intractable seizures. This process assessment examined the effectiveness of trial interventions of cuing and coaching on strategy use to facilitate learning in a classroom setting. After analysis and interventions, the boy showed a 20% increase in time engaged in instruction and learning. Summary and recommendations Studies in this medical area focused on treatment of attention and memory, domains frequently affected by seizure disorders. Class II and class III studies that were reviewed, with a total of 156 subjects, had in common both training to improve attention and memory performance and teaching of techniques to promote internalization of strategy use. These studies allow for the recommendation as a Practice Option that CR for attention and memory decits, with additional techniques for internalization of strategy use, may be effective for individuals with seizure-related decits in attention and memory. It is recommended that further CR research involving individuals with seizure disorders consider including strategy use as a specic component of training.

281 3- and 5-month booster sessions. Outcome assessment was by blinded neuropsychologists at baseline, 6 weeks, 4 months, and 6 months after enrollment on the Mini-Mental State Examination and the Mental Deterioration Battery. Baseline impairment was evident on approximately one third of measures. No improvements were noted in either group after treatment, although functioning did not deteriorate, and no between-group differences were found. Goldberg and Ellis35 evaluated an intervention in a severely impaired patient with diagnosed anoxic encephalopathy secondary to cardiac arrest, seeking to improve executive self-management of bowel/bladder continence and negative and positive behaviors using procedural learning channels. After a 6-week baseline, treatment by reinforcement of desired behaviors was initiated and maintained for 6 months. Signicant improvements in all target behaviors were noted at follow-up. McLean et al36 used an ABA design to examine the benets of memory and orientation training combined with physostigmine in 2 patients with carbon monoxide poisoning. Self-instruction methods designed to generalize across situations were used for a treatment duration of 6 weeks in 1 case, and 3 weeks in the other. In both cases, memory performance improved with treatment and declined when treatment was withdrawn. Summary and recommendations An RCT involving 105 subjects, with blinded assessment, failed to show additive benets for 10 sessions of CR compared with standard medical treatment alone in patients with COPD-related hypoxemia. Two class IV studies, both single-subject designs, suggested benets in using operant conditioning and memory and orientation training in combination with physostigmine. There is currently insufcient evidence to recommend or contraindicate the use of CR in individuals with cognitive impairment from anoxia or hypoxia. Individuals with anoxic/hypoxic events or disorders often show signicant, and at times deteriorating, impairment. It is recommended that foundation CR research with this population begin with single-subject or small-sample studies with careful subject selection (ie, individuals screened for relatively milder decits and indications of learning potential), using targeted interventions, and aimed at measurable functional goals.

Anoxia/hypoxia
Cerebral hypoxia and anoxia result from decreased or complete deprivation of brain oxygen supply, respectively. Hypoxia can occur with conditions that interfere with breathing, blood oxygenation, or both, including severe asthma, chronic obstructive pulmonary disease (COPD), anemia, exposure to nitrogen-rich environments, and intense high-altitude exercise. Severe cerebral hypoxia/anoxia often has a traumatic etiologydfor example, choking, drowning, strangulation, carbon monoxide poisoning, drug overdose, status asthmaticus, or electric shock. Anoxic brain damage affects the hippocampus, parieto-occipital-temporal watershed areas, neocortex, prefrontal lobe, and cerebellum, and in severe cases, the basal ganglia. Cognitive effects include difculty with new learning, attention/concentration, information processing, executive function, and emotional regulation. Three articles evaluated CR for individuals with anoxic/ hypoxic injuries. One was rated class I,34 and the other 2 singlesubject design studies were rated class IV.35,36 Incalzi et al34 conducted an RCT involving 105 patients with COPD complicated by chronic hypoxemia, a degenerative disease causing an abnormally low arterial blood oxygen concentration. Participants were randomly assigned to receive standardized multidimensional care either with or without concomitant CR. Standardized multidimensional care included pharmacologic therapy, health education, inhaler use, respiratory rehabilitation, nutritional counseling, oxygen therapy, and follow-up visits to measure compliance. CR comprised attention training (eg, visual cancellation tasks of increasing complexity), memory training (eg, critical thinking and active reading techniques), and exercises for logical, deductive thinking (eg, classication and reasoning tasks). The CR was conducted in 6 group sessions over 2 weeks, followed by 4 individual sessions over 4 weeks, with home assignments and www.archives-pmr.org

Encephalitis
Encephalitis is most frequently caused by viral infection producing inammation of the brain and meninges, often with resulting swelling and hemorrhage. Herpes simplex virus and St. Louis virus are the 2 most common viral infectious agents, with herpes simplex virus primarily affecting limbic structures and the medial/lateral temporal and orbitofrontal cortices, and St. Louis virus primarily affecting the meninges and subcortical structures. Cognitive decits depend on affected brain areas, although memory decits are most typical and prominent. The 8 studies reviewed in this diagnostic area, all either singlesubject experiments or case studies, were rated as class IV.37-44 Four case reports or single-subject studies37-40 investigated either the use of external aids or strategies to improve memory performance. The use of a wearable camera that takes pictures automatically every 30 seconds was found to be more effective than a written diary in improving autobiographical recall for a woman with severe memory impairment, with carryover effects evident after 3 months.37 The use of a paging system for prospective memory tasks resulted in improved completion of target behaviors

282 when using a pager, with reduced carryover without the pager, for 3 subjects.40 These results, similar to those obtained with a comparable TBI group, supported the use of a pager for individuals with moderate to severe memory decits. Use of a memory notebook was associated with improved memory management in 2 singlesubject studies,38,39 the latter subject returning to her job 8 months postillness. In a woman with impaired word nding for objects and names, a verbal semantic association strategy reduced word-nding errors for objects, and a visual face-name association procedure reduced error frequency.41 With the use of errorless-learning techniques,45 strategies for learning face-name associations and remembering text were taught to a 44-year-old amnestic man.42 Motor imaging was found to be superior to visual imagery for frequency of facename associations, and active reading techniques were more effective than verbal rehearsal for text recall. A case study reporting on successful hierarchical training in attention, working memory, and processing speed in a mildly impaired woman noted that she was able to resume her previous workload after treatment.43 Finally, a behavior modication program with verbal mediation to chain 9 tasks was successful in improving physical hygiene in a man with severe amnesia and behavioral problems, with maintenance at 3-month follow-up.44 Summary and recommendations There is currently insufcient evidence to make recommendations for the use of CR with postencephalitis cognitive decits. However, studies in this diagnostic area provide useful ideas for further research. For example, external memory aids or strategies engaging implicit and procedural memory systems are theoretically plausible in a population showing signicant memory dysfunction. Building research on these methods, advanced via pilot studies that explore the most suitable subject characteristics for success, would be a reasonable next stage for this medical population.

D.M. Langenbahn et al practice versus PT alone in treating motor and functional performance impaired by idiopathic PD.47 Participants were randomly assigned to either combined (nZ12) or PT-alone (nZ11) treatment after stratication by age, sex, and disease stage. PT-alone treatment consisted of callisthenic exercises, functional tasks, and relaxation exercises. Combined treatment included these elements as well as structured training in symbolic, external, and internal imagery. Blinded outcome measurement comprised both physical and cognitive assessment. Results indicated better performance by the combined treatment group on movement sequences, and larger gains on mental and motor subtests of a standardized PD rating scale as well as on cognitive tests. In a class IV study, Kamsma et al48 also outlined a strategybased procedure for learning and executing a sequenced activity, and trained 10 outpatients using instructive video, error correction via video and discussion, and both physical and mental practice. Self-instruction was used for internalization of strategy use. Errors for all participants decreased across training, with a slower learning curve associated with greater motor impairment. In the nal class IV study, Sinforiani et al49 found gains on tests of story memory, phonemic uency, and visual matrices in a 6-week case series study treating 20 patients with PD using software aimed at stimulating attention, abstract reasoning, and visuospatial abilities at different levels of complexity across different modalities. Gains were maintained at 6-month follow-up assessment. Summary and recommendations Although this literature indicates positive results in areas of memory and executive functioning, there is insufcient evidence to make recommendations for CR for individuals with PD. The studies reviewed, however, provide a basis for the design of more advanced projects exploring the potential for CR in assisting this population with the physical and other everyday life challenges brought by PD. It is recommended that research be conducted in postacute contexts, to avoid obscuring the effects of CR by its being embedded in inpatient rehabilitation programs.

Parkinsons disease
PD is a degenerative disorder caused by insufcient formation and action of dopamine in the substantia nigra, resulting in decreased stimulation of the motor cortex via the basal ganglia. Secondary symptoms include high-level cognitive dysfunction and subtle language problems. Stages of PD are based on physical criteria that have an unclear relationship to cognitive involvement. The possible presence of dementia and current dosages of antiparkinsonian medication also impact cognitive functioning. Review of evidence for CR effectiveness for individuals with PD resulted in the classication of 4 articles, with 1 class II study, 1 class III study, and 2 class IV studies. In the class II study, Sammer et al46 compared 2 groups of 13 participants each; 1 group received CR, while the other received standard treatment. Participants were randomly assigned, although it was not reported that blinding of assessments was done. The cognitive training condition consisted of ten 30-minute sessions with a set of working memory tasks requiring executive functions. Results of measures of working memory and executive functioning indicated that immediately posttreatment, the group receiving CR performed better than the control group on executive functioning tasks requiring rule shift and the ability to organize performance among several subtasks. The class III study engaged 23 patients in a cohort comparison study of combined physical therapy (PT) and motor imagery

Toxic encephalopathy
Toxic encephalopathy refers to brain damage and dysfunction caused by the effects of toxins or chemicals. The most prominent characteristic of acute toxic encephalopathy is altered mental status, sometimes delirium. Lasting toxic encephalopathy can have a wide variety of physical symptoms, including involuntary movements, nausea, fatigue, seizures, and decreased strength. Primary cognitive symptoms are memory decits and decreases in attention/concentration and executive functioning. There was 1 study50 reviewed in this area, a class II RCT/ crossover study involving 95 patients with a diagnosis of solventinduced chronic toxic encephalopathy and either a moderate or a high level of exposure. All participants had memory decits on standardized neuropsychological tests and were randomly assigned to 1 of 2 treatment groups (in which an 8-session sequence of 2 treatments was alternated) or a waitlist control group. The 2 treatments were psychosocial treatment and cognitive strategy training, the rst consisting of 8 weekly 2-hour sessions of psychoeducational group therapy based on cognitive behavioral principles, with goals of increasing awareness and acceptance of decits. The second treatment focused on developing compensatory memory strategies; participants learned about www.archives-pmr.org

Cognitive rehabilitation in medical conditions memory aids in three 2-hour group sessions, followed by four 45-minute individual sessions covering learning and practice of internal memory strategies, and a nal summarizing session. Although treatment order was counterbalanced, data from the 2 treatment groups were combined. Results of objective measures of memory functioning and subjective (participants and their partners) report of memory complaints and psychosocial functioning were analyzed. At posttest, between-group comparisons on 3 outcome measures reached borderline signicance; treatment groups had higher memory scores and fewer memory complaints than controls, but more health-related complaints (perhaps because of increased awareness). Only differences in memory complaint scores prevailed at 3-month follow-up. Overall satisfaction with treatment among participants was high immediately after treatment and at 3-month follow-up, and older treated participants showed relatively greater memory score improvement at posttesting. Summary and recommendations There is insufcient evidence to date to support putting forward a treatment recommendation in this area. The only study in this diagnostic area offers some support for improved memory functioning with training in strategy use, but insufcient effect strength, and little or no evidence for lasting training effects or continued strategy use. Research development is suggested via pilot studies exploring the potential benets of memory strategy interventions, with attention to selection of suitable subject characteristics for optimizing intervention success.

283 across time as an indicator of successful treatment, is an appropriate design for individuals with this degenerating condition.

Systemic lupus erythematosus

SLE-related cognitive decits, as well as the occurrence of seizures, strokes, and headaches, reect CNS involvement thought to be associated with autoantibodies that accelerate cardiovascular disease.52,53 Individuals with SLE may also develop secondary CNS vasculitis.53 Studies of cognitive dysfunction in individuals with SLE suggest a prevalence ranging from 17% to 59%, most frequently involving general intelligence, verbal learning/memory, visuospatial skills, psychomotor speed/manual dexterity, and attention/mental exibility.52 One nonrandomized, uncontrolled pilot study54 with this population was reviewed and rated as class IV. Authors pretested 17 individuals with measures of mood and social support, as well as indices of memory and metamemory (eg, awareness of memory capacity/limits and strategy use). Training took place over 8 weeks and consisted of a once-weekly, 2-hour psychoeducational group session combining functional strategy training and psychosocial support. Results indicated improved metamemory and functional memory scores, with no change in psychosocial support. Summary and recommendations There is insufcient evidence to date to support a treatment recommendation in this area. It is recommended that researchers of this population focus in areas of cognitive difculty also common to other diagnostic groups (eg, attention and/or memory), select individuals with identiable, yet treatable decits, and choose intervention methods based in process training and strategy use.

Huntington disease
HD is a neurodegenerative disorder caused by a chromosomal anomaly. Onset is typically between the ages of 30 and 50 years, with a deteriorating disease course of 15 to 20 years. Treatment with medication provides time-limited symptomatic relief. First and primary symptoms are choreic movements and facial tics, as well as dystonia, bradykinesia, hypokinesia, akinesia, and dysarthria. Dysphagia occurs in later stages. Cognitive impairment, primarily affecting memory and reasoning capacity, is also progressive. One class IV article51 on the effectiveness of CR for individuals with HD met criteria for review. In this examination of intensive inpatient treatment, CR was embedded in an interdisciplinary program with respiratory exercises and physical, occupational, and speech therapies. Forty participants with early- or middle-stage HD were tracked for 2 years, providing a withinsubject comparison in a case series design. CR was aimed at prolonging attention span and teaching metacognitive strategies and the use of external memory aids. Maintenance of initial test score levels on cognitive and emotional measures across the 2-year period was interpreted as a demonstration of program effectiveness in preventing cognitive deterioration despite physical decline. Summary and recommendations There is insufcient evidence to date to support putting forward a treatment recommendation in this area. Nonetheless, we believe that the study reviewed here represents a potentially fruitful line of research to examine the effectiveness of CR in this population. A within-subjects comparison, with stability in cognitive functioning www.archives-pmr.org

Discussion
Our review of the efcacy of CR in the treatment of cognitive problems associated with brain neoplasms, anoxia, encephalitis, epilepsy, PD, HD, toxic encephalopathy, and SLE resulted in 2 recommendations for clinical treatment being advanced. These recommendations are in the diagnostic areas of brain neoplasms and epilepsy/seizure disorders (table 5). The body of intervention research across the medical diagnostic areas that we reviewed is in early stages compared with the evidence available for individuals with TBI or stroke, which are the predominant diagnostic groups in rehabilitation practice. The current review found few appropriate studies in each diagnostic area and a lack of controlled intervention research, with only 1 study34 meeting criteria for class I designation. That study did not yield support for the use of CR but, signicantly, involved a population with a deteriorative, rather than static, medical condition. Despite the limitations found in the research, several trends are apparent. The domains targeted for CR logically reect cognitive functions most commonly affected by the medical condition. In the 3 diagnostic areas with the most research studiesdbrain neoplasms, epilepsy, and encephalitisdtreatment interventions include many of those shown to be effective in individuals with TBI or stroke (eg, APT-based attention training, internalization of strategy use, use of external or internal memory aids), or innovative techniques based on a strong clinical rationale (eg, a wearable camera to record events in the case of postencephalitic amnesia). In the context of degenerative disorders such as HD and PD, examination of the effectiveness of CR has taken into account

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Table 5 Practice recommendations resulting from current review

D.M. Langenbahn et al

Practice Guideline: The use of process-based CR strategies (eg, APT, strategy acquisition and internalization, self-monitoring, and corrective feedback) is probably effective in treating attention and memory decits in children and adolescents who undergo resection and/or radiation after diagnosis of brain neoplasm. Practice Option: The use of CR for attention and memory decits, including techniques for internalization of strategy use, is possibly effective for individuals with seizure-related decits in attention and memory.

the natural course of the disease process. It is not unreasonable to think that the effectiveness of CR can then be demonstrated appropriately by a relative stability or a slower decline in cognitive function compared with changes in the absence of treatment. In evaluating the current state of this research and making recommendations for future research development, it may be impractical and premature to call for the accrual of more class I research without considering some of the realities of these diagnostic groups as represented in the rehabilitation population. First, their combined base rates often comprise a small proportion of the clinical rehabilitation population. Thus, the probability of amassing enough patients in single treatment centers to conduct RCTs is substantially less than for populations of individuals with TBI or stroke. Second, in part because of lower population numbers, and thus less advocacy capacity, the funding necessary to support such studies is very limited. Finally, any RCTs conducted should be informed by well-grounded lines of theorydriven, preliminary research to support the assessment of feasibility and ensure well-designed efcacy trials.55 Unfortunately, this is not the case for most of the studies currently reviewed. They represent a loose conguration of treatment approaches, and although some interventions are theory-driven, with the exception of approaches to attention and memory training, there are few indications of a consistent CR approach apparent either within or between diagnostic groups. As has been argued elsewhere, researchers should support and promote the development and maturation of a treatment program before considering an RCT.55-57 It is rst important to determine the natural history of the neurologic disease or disorder, the impact of that course on physical, cognitive, and functional parameters, the primary cognitive treatment targets, and reliable methods for their measurement. Understanding the impact of factors such as the severity of impairment, time postonset, and comorbidities (including psychosocial issues) is also crucial.57 Initial goals include the specication of a treatment population and targeted decit area expected to benet from an intervention, the formation of a realistic and benecial treatment protocol, the selection of outcome measures sensitive to near treatment effects, and initial evidence about the magnitude of the treatment effect.57 Finally, it is important that CR interventions be grounded in an understanding of the development and organization of human cognitive processes. We suggest that such careful research planning must form the basis for further studies on the efcacy and effectiveness of treatment interventions in these diverse medical population groups. Well-constructed class IV case studies, or class III multiple-baseline studies with rm theoretic rationales for interventions, are ideal vehicles for initiating steps toward these goals. CR approaches found to be effective in treatment of cognitive decits after TBI and stroke may be ideal models in this task. Recommendations that have now been articulated across several cognitive domains1-3 can be examined for applicability with other neurologic diagnostic groups. Possible areas for fruitful development include exploration of the use of strategy training for

attention decits, structured training in memory notebook use for individuals with memory impairment, and training in selfmonitoring and self-regulation in the rehabilitation of executive dysfunction.1 There also are possible avenues toward developing an appropriate evidence base to guide the use of CR in medical populations of low incidence and/or rarely seen in rehabilitation settings. Some of these groups may be treated in specialized clinics, appropriate for conducting clinical trials and even multicenter collaborations. Multicenter international trials that capitalize on the availability of specialized, condition-specic care centers outside the United States (eg, Scho n-Klinikin for PD throughout Germany, London Lupus Center) may also address the problem.

Study limitations
As a nal point, the extent and limitations of the applicability of an EBR should be considered. We strongly support the philosophy and procedures of EBR methodology, as well as the translation of EBR results into clinical practice. However, just as we have exercised caution in deriving recommendations from the existing evidence for the effectiveness of CR in the diagnostic areas examined, we must also caution against concluding that CR is not effective in treating cognitive decits resulting from these etiologies. A lack of adequately designed studies is a methodological issue, not proof of ineffectiveness. On the contrary, the wise clinician assesses the theoretic and practical information to be gained from the research and integrates that information with his/ her clinical knowledge and experience. Many of the cognitive decits apparent in the groups examined herein have functional familiarity that clinicians have treated and will continue to treat with CR interventions. We support this practice, not only because of our belief in the merit of expert clinical opinion, but also because of the hope and expectation that treatment efforts will be paired with appropriate research methodology ultimately to add greater substance to this body of evidence.

Conclusions
This CRTF subgroup of the BI-ISIG of the American Congress of Rehabilitation Medicine reviewed an initial 211 studies of CR published before 2009 across 11 categories of medical diagnoses. A total of 34 admissible studies was found and fully reviewed for only 8 diagnoses. There is sufcient evidence to support treatment recommendations at this early stage of research in only 2 of the examined diagnostic areas. We suggest that future studies be designed based on knowledge of the conditions underlying pathology, occurrence, severity, and possible course; the use of measures best suited to expected change; and employment of interventions found to be effective with similar decits in individuals with TBI or stroke. Further, theoretically based, wellconstructed class III and IV studies in each diagnostic category www.archives-pmr.org

Cognitive rehabilitation in medical conditions will lay the necessary groundwork for later RCTs where possible. Such theories should be based on constructs of human cognitive processes and their inherent hierarchy of cognitive development and organization.

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Keywords
AIDS; Anoxia; Cognition; Cognitive; Encephalitis; Encephalopathy, toxic; Epilepsy; Evidence; HIV; Huntington disease; Lyme disease encephalopathy; Neoplasms; Parkinson disease; Rehabilitation; Review; Systemic lupus erythematosus

Corresponding author
Donna M. Langenbahn, PhD, Rusk Institute of Rehabilitation MedicineeACC, 240 E 38th St, Room 1721, New York, NY 10016. E-mail address: donna.langenbahn@nyumc.org.

Acknowledgment
We thank Keith D. Cicerone, PhD, for critical review of this article.

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