COGNITIVE REHABILITATION
Study
Main Purpose
Research
Design
Rehabilitative Treatment of Cognitive Deficits
Sample
Outcome
Measures
Results
Study Type
Level of
Evidence
Salazar et al.,
2000
Evaluate the efficacy of
cognitive rehabilitation
for patients with TBI
Randomized,
parallel-group
controlled trial
120 active duty
military
personnel who
sustained
moderate-severe
TBI, an average
of 38 days postinjury
Return to work
(RTW) and fitness
for duty at 1-year
follow-up
Therapeutic
intervention
I
Cicerone et
al., 2004
Compare the impact of
intensive cognitive
rehabilitation and
standard neurorehabilitation on community
integration
Nonrandomized,
controlled
intervention
CIQ, Quality of
Community
Integration
Questionnaire
Therapeutic
intervention
II
Goranson et
al., 2003
Evaluate multidisciplinary
treatment, including
cognitive rehabilitation
Retrospective
cohort study
CIQ
Rehabilitation group
showed greater
improvement on overall
CIQ and Home
Integration subscale
Therapeutic
intervention
III
Klonoff et al.,
1998
Evaluate outcome of
milieu-oriented
neurorehabilita-tion,
adjusted for admission
level of functional
impairment
Pre-post
Productivity at
discharge, adjusted
for staff ratings of
functional severity
at admission
89.5% of patients showed
fair or good adjusted
outcome, 62% gainfully
employed, 15.6%
resumed preinjury status.
Therapeutic
intervention
IV
Malec, 2001
Evaluate comprehensive
day treatment
(CDT) for survivors of
brain injury, by time since
injury and identify
outcome predictors
Pre-post
27 individuals
with TBI who
received
intensive
rehabilitation
and 29 who
received
standard
rehabilitation
Archival data for
21 subjects with
TBI who
received
treatment and 21
subjects who did
not receive
rehabilitation
64 patients with
acquired brain
injury (37 TBI)
consecutively
admitted to
outpatient
neurorehabilitati
on program
96 program
graduates; 17
dropouts with
acquired brain
injury (81 with
TBI)
No difference between inhospital cognitive
rehabilitation vs. limited
home program; subset
analysis of patients with
LOC>1 hour (n=75)
showed greater RTW
after cognitive
rehabilitation.
Both groups improved,
but intensive program
participants were much
more likely to show
improved community
integration.
Independent living
status, vocational
independence
scale, MPAI-22
and goal attainment
scaling
components
Significant goal
achievement on GAS and
improvement on MPAI22; increased societal
participation, 72% of
graduates living
independently, 39%
Therapeutic
intervention
Prognostic
IV
Seale et al.,
2002
Evaluate changes in
community integration for
survivors of TBI who
participated in post-acute
rehabilitation
Pre-post
Sohlberg et
al., 2000
Evaluate Attention
Process Training (APT),
compared with a brain
injury education
“placebo”
Randomized,
crossover
design with
parallel-group
analyses
Fasotti et al.,
2000
Evaluate Time Pressure
Management (TPM) to
compensate for slowed
processing, compared
with generic
concentration instructions
Randomized,
parallel-group
controlled trial
Berg et al.,
1991
Evaluate the efficacy of
memory strategy training,
compared with
‘pseudotreat-ment’ (drill
and practice) and notreatment conditions
Evaluate visual imagery
for remediation of
memory deficits,
compared with
‘pragmatic’ memory
training
Randomized,
parallel-group
controlled trial
Evaluate memory
notebook training,
compared with supportive
Randomized,
parallel-group
controlled trial
Kaschel et al.,
2002
SchmitterEdgecombe et
al., 1995
Randomized,
parallel-group
controlled trial
71 subjects with
TBI who
participated in a
postacute
rehabilitation
program
14 subjects with
acquired brain
injury (12 TBI),
more than 1 year
post injury
22 subjects with
severe to very
severe TBI, at
least 3 months
post-injury,
referred to one
rehabilitation
center
39 subjects with
mild memory
impairment,
most at least 1
year post TBI
21 subjects with
acquired brain
injury (12 TBI)
with mild
memory
impairments, at
least 6 months
post injury
8 subjects with
TBI, with mild
memory
CIQ
Standardized
questionnaires,
data from
structured
interviews,
standardized and
non-standardized
neuropsychological tests
Standardized
behavioral
observations of
strategy use,
standardized
neuropsychological tests
Standardized
memory testing,
subjective report of
memory
functioning
Observed and selfreported memory
failures
Standardized
neuropsychological tests of
working
independently, 10% in
transitional placements,
18% in
supported or volunteer
work.
Significant improvement
on CIQ and all subscales.
Clinically significant
improvement on CIQ total
for 46% of subjects; 49%
no change; 4% got worse
APT related to
significantly greater
improvement on 3 of 5
neuropsychological tests;
significantly more
changes reported in
memory and attention.
Therapeutic
intervention
IV
Therapeutic
intervention
I
TPM produced significant
increase in use of
management strategy and
summary measure of
cognitive function.
Therapeutic
intervention
I
Both treatment groups
reported subjective
improvement; objective
improvement of memory
function apparent only
after strategy training.
Visual imagery produced
domain-specific benefits
on retention of verbal
information.
Therapeutic
intervention
I
Therapeutic
intervention
I
Notebook training related
to fewer self-reported
everyday memory failures
Therapeutic
intervention
I
therapy
Levine et al.,
2000
Evaluate problem-solving
training, compared with
motor skills training
Rath et al.,
2003
Compare an “innovative”
group treatment of
problem-solving deficits
with “conventional”
neuropsycho-logical
treatment
impairment,
more than 2
years post injury
attention and
memory; selfreported everyday
memory failures
Standardized and
non-standardized
neuropsychological tests
after treatment; difference
between groups no longer
apparent at 6-month
follow-up.
Problem solving training
related to specific
improvements on nonstandardized tests.
Randomized,
parallel-group
controlled trial
(no masked
outcome
assessment)
Randomized,
parallel-group
controlled trial
(no direct
comparison of
treatment
conditions)
30 subjects with
mild-to-severe
TBI, 3 to 4 years
post injury
Therapeutic
intervention
III
46 subjects with
mild-to-severe
TBI, at least 1
year post injury,
drawn from a
large outpatient
treatment
program
Standardized and
non-standardized
neuropsychological
tests
Both groups improved on
various measures;
innovative problemsolving treatment related
to improvement on
problem-solving
measures.
Therapeutic
intervention
III
Randomized,
double-blind,
parallel-group
controlled trial
comparing
phenytoin for
1 week, VPA
for 1 month or
VPA for 6
months
Single case
study
279 consecutive
medical center
admissions,
randomized at 1month postinjury
Battery of
neuropsychological
measures
administered at 1 ,6
and 12 months
post-injury
No significant adverse or
beneficial effects of VPA.
Therapeutic
intervention
I
38-year-old man
in MCS five
months after
sustaining a
severe TBI
35 adults with
moderate or
severe TBI
recruited within
6 months of
injury
Coma-Near Coma
(CNC) Scale
Therapeutic
intervention
IV
Therapeutic
intervention
III
74 patients with
severe TBI
admitted to an
ICU in coma
Glasgow Coma
Scale (GCS) and
mortality rates
Dose-dependent
improvement of CNC
scores was found after
treatment with
amantadine.
No detrimental effects of
amantadine on laboratory
studies. Improvement on
DRS and FIM-Cog, with
no difference between
drug and placebo
treatments at 12 weeks or
6 months.
Higher GCS on discharge
from ICR and lower case
mortality rates with
standard therapy plus
Therapeutic
intervention
II
Drug Treatment of Cognitive Deficits
Dikmen et al.,
2000
Evaluate neuropsychological effects of
valproate (VPA) given to
prevent post-traumatic
seizures
Zafonte et al.,
1998
Evaluate amantadine in
treatment of prolonged
minimally conscious state
(MCS)
Meythaler et
al., 2002
Evaluate the safety and
efficacy of amantadine in
TBI
Randomized,
double- blind
placebocontrolled
cross-over
design
Saniova et al.,
2004
Investigate the therapeutic
effects of standard
therapy alone versus
standard therapy plus
Retrospective
cohort study
Disability Rating
Scale (DRS),
MiniMental Status,
GOS, GOAT, FIMCog score
amantadine
amantadine.
Meythaler et
al., 2001
Evaluate impact of an
SSRI (sertraline) in
improving arousal and
alertness after TBI
Prospective,
placebocontrolled,
parallel-group
design
Whyte et al.,
2004
Evaluate the effects of
methylphenidate on
attention deficits after
TBI
Randomized,
double-blind,
placebocontrolled,
repeatedmeasures
cross-over
design; withinsubjects
analyses only
Whyte et al.,
1997
Evaluate the effects of
methylphenidate on
attention deficits after
TBI
Zhang et al.,
2004
Examine effects of
donepezil on short-term
memory and sustained
attention
Randomized,
double-blind,
placebocontrolled,
repeatedmeasures
cross-over
design; withinsubjects
analyses only
Randomized,
double-blind,
placebocontrolled
cross-over
design
Taverni et al.,
1998
Evaluate the impact of
donepezil in acute TBI
rehabilitation
Case series
Masanic et
al., 2001
Evaluate the impact of
donepezil in chronic TBI
Open label,
uncontrolled
study
11 patients with
severe TBI
admitted to
inpatient
rehabilitation
within 2 weeks
of injury
34 adults with
moderate to
severe TBI with
attention
complaints, in
postacute phase
of recovery (4
months to 34
years postinjury)
Orientation Log,
GOAT, Agitated
Behavior Scale
No differences in rates of
recovery between groups.
Therapeutic
intervention
III
Various
experimental
attention measures,
including
computerized and
paper-pencil tests,
videotape and
observational
scoring, caregiver
and clinician rating
scales
5 experimental
measures of
attention
Significant effects of
methylphenidate on 3 of
13 composite attention
factors: processing speed,
attentiveness during
individual work tasks and
caregiver ratings.
Therapeutic
intervention
III
Significant benefits of
methylphenidate on
processing speed.
Therapeutic
intervention
III
18 subjects with
cognitive
impairment
enrolled from
out-patient
neurorehabilitati
on clinics, 2 to
24 months postTBI
2 persons with
TBI admitted to
acute inpatient
rehabilitation
Standardized
neuropsychological tests of
immediate memory
(WMS-III) and
attention (PASAT)
Significant benefits of
donepezil on immediate
memory and attention.
Therapeutic
intervention
I
Family interviews,
memory testing
Therapeutic
intervention
IV
4 outpatients
with chronic TBI
symptoms
Verbal learning,
short-term and
long-term recall
Improvement of memory,
both subjectively and
objectively assessed,
within 3 weeks of start of
medication.
Significant improvement
in tests of verbal learning
and short-term and long-
Therapeutic
intervention
IV
19 adults with
perceived
attention
problems after
TBI
term recall.
Morey et al.,
2003
Investigate the
effectiveness of donepezil
in treating memory
deficits after TBI
ABAC drug
trial
7 persons who
had sustained
TBI at least 1.5
years prior
Horsfield et
al., 2002
Evaluate the role of
fluoxetine in the
outpatient TBI setting
Evaluate the impact of
bromocriptine in
experimental chronic TBI
Open label,
uncontrolled
study
Controlled
animal trial
5 outpatients
with TBI
Powell et al.,
1996
Evaluate the effects of
bromocriptine on deficits
in clinical motivation and
frontal cognitive function
Repeatedmeasures open
trial
Schneider et
al., 1999
Evaluate the efficacy of
amantadine in improving
cognitive and behavioral
performance after TBI
Randomized,
double-blind,
placebocontrolled
cross-over
design
10 adults with
TBI receiving
acute brain
injury
rehabilitation
Examine the utility of
neuropsycho-logical
measures of executive
functioning as predictors
of functional ability and
social integration
Prospective,
descriptive
study
90 consecutive
admissions to
TBI (45),
orthopedic (13)
and spinal cord
(32) inpatient
rehabilitation
units
Kline et al.,
2002
Male rats, given
cortical impact
injury and, in
experimental
group, daily
bromocriptine 24
h later
11 patients (8
TBI, 3
subarachnoid
hemorrhage)
receiving
rehabilitation
Hopkins Verbal
Learning,
Wechsler Adult
Intelligence Scale,
Controlled Oral
Word Association
Test (COWAT)
Working memory
tasks, assessment
of mood
Cellular studies,
animal memory
tests
Significant improvement
in tests of immediate and
delayed memory, at doses
of 10 mg/day.
Therapeutic
intervention
III
Improved mood and
performance on working
memory tasks.
Bromocriptine improved
working memory and
spatial acquisition skills;
experimental group had
improved preservation of
CA3 neurons.
Therapeutic
intervention
IV
Therapeutic
intervention
(animal
model)
NA
Experimental
measures of
therapy
participation and
responsiveness to
reward,
standardized
neuropsychological tests of
cognitive function
and mood
Standardized
neuropsychological
tests
Improved scores on all
measures except mood;
improvement remained
even after bromocriptine
withdrawal in 8 of 11
patients.
Therapeutic
intervention
IV
No significant difference
between amantadine and
placebo.
Therapeutic
intervention
I
CIQ, DRS, SF-36
Neuropsychological
measures of memory and
executive function were
significant predictors of
CIQ and DRS at 6 months
after inpatient
rehabilitation.
Prognostic
II
Prognosis
Hanks et al.,
1999
Millis et al.,
2001
Describe neuropsychological outcome 5 years
after injury in persons
with TBI who received
inpatient rehabilitation
Longitudinal
cohort study,
using TBI
Model System
data
182 subjects with
complicated
mild-to-severe
TBI
Standardized
neuropsychological measures,
administered 1 and
5 years after injury
Ezrachi et al.,
1991
Identify factors that
predict who will benefit
vocationally from a
neuropsycho-logical
rehabilitation program
Prospective,
descriptive
study
59 people with
moderate-tosevere TBI who
participated in a
holistic
neuropsychologi
cal rehabilitation
program
Employability
ratings at
discharge, actual
vocational status 6
months later
Tenovuo,
2005
Examine the clinical
experience of persons
given ACE in the
treatment of TBI
Open label,
multiple-arm
trial of
donepezil,
galantamine
and
rivastigmine
111 outpatients
with chronic TBI
and persistent
attention,
memory, fatigue
or initiation
complaints
Fatigue measures,
general memory
and attention
Age and length of PTA
significant predictors of
Trail B performance at 5
years postinjury; memory
function (RAVLT) at 1
year predicted
improvement at Year 5.
Neurologic (length of
coma),
neuropsychological
(verbal memory, visual
processing, verbal
aptitude) and group
process (regulation of
affect, self-appraisal,
acceptance of program)
measures all contributed
to predicting outcome.
Prognostic
III
Prognostic
III
61% with a significant
positive response to
medications, 39% with
modest improvement. No
differences between the
three ACE drugs
Therapeutic
intervention
III