Cognitive Impairment
Conditions
Brief summary
The investigators hypothesis are as follows: H1a: OEF/OIF veterans with PTSD who perform cognitive training (CT) will demonstrate greater objective improvements on standard (untrained) neurocognitive measures, with the largest gains in verbal memory, learning and sustained attention. H1b: Objective cognitive improvements in CT participants will be sustained at three months post-intervention, suggesting persistence of neuroplasticity-based cognitive training benefits. H2a: OEF/OIF veterans with PTSD who perform CT will report greater improvements in cognitive function. H2b: OEF/OIF veterans with PTSD who perform CT will demonstrate improved social and occupational functioning and quality of life. H2c: OEF/OIF veterans with PTSD who perform CT will demonstrate greater improvements in community reintegration.
Detailed description
Posttraumatic Stress Disorder (PTSD)-related cognitive dysfunction is well-described and has been associated with specific impairments in verbal memory, learning, attention and emotional regulation, deficits which have been correlated with abnormalities in specific brain regions. Both PTSD and cognitive dysfunction have been associated with impairments in social and occupational functioning and may contribute to operational or battlefield errors, soldiers' safety and threaten the success of military operations. In addition, following military service separation, PTSD-related cognitive impairment adversely impacts quality of life, readjustment, and community reintegration. A computerized neuroplasticity-based auditory cognitive training program (Plasticity-Based Adaptive Cognitive Remediation, Posit Science, San Francisco, CA) has been shown in several randomized controlled trials to improve verbal memory, attention, cognitive control, quality of life and daily function in community-dwelling elders and individuals with schizophrenia. To our knowledge however, there have been no studies of cognitive remediation training in individuals with PTSD. Therefore, the overall aim of this proposal was to investigate the efficacy of neuroplasticity-based auditory cognitive training in Veterans with PTSD and cognitive dysfunction. The primary specific aim of this pilot study was to examine change in objective cognitive function in Veterans with PTSD and cognitive dysfunction who participated in an open-label trial of an auditory cognitive training program. Our secondary aim was to examine change in self-reported cognitive function, social and occupational functioning, quality of life and community reintegration in Veterans with PTSD who participate in auditory CT. Finally, we evaluated the feasibility and usability of home-based computerized auditory cognitive training in Veterans with PTSD and cognitive dysfunction. We enrolled subjects in a program of 3 months of auditory cognitive training (CT) followed by 3 months of no contact. We assessed participants' change scores on neuropsychological outcome measures from pre- to post-treatment using reliable change indicators. We utilized qualitative thematic analysis to identify themes from participants about the feasibility, acceptability, and usability of the treatment. Information derived from this pilot study may be used to inform future cognitive training interventions for Veterans.
Interventions
BEHAVIORALCognitive Training
Plasticity Based Adaptive Cognitive Remediation (PACR)
Sponsors
Karen Seal
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* An experienced clinical interviewer with Master's-level training will conduct first- and second-level screening to determine study eligibility for enrollment in the randomized controlled trial. * The First-Level Eligibility Screen will be conducted by phone and will apply the following inclusion criteria in an effort to recruit a homogeneous sample: 1. Confirmed OEF and/or OIF military service 2. Male veterans, ages 18 to 40 years with 12 to 16 years of education 3. History of a prior positive PTSD screen or diagnosis either by SFVAMC study referral or self-report' 4. Able and willing to travel to SFVAMC 5. Able and willing to perform daily home-based computer exercises for three months. * The Second Level Eligibility Determination will occur in-person at the SFVAMC of potential participants who have met first-level screening eligibility criteria. Second-level eligibility screening will require signed informed consent (see below) before the second-level screening is conducted. During the second-level eligibility screen, consenting participants will be administered: 1. The Clinician-Administered PTSD screen (CAPS) and the Mini International Neuropsychiatric Interview (MINI) 29 to assess for Diagnostic and Statistical Manual (DSM)-IV Axis I psychiatric disorders 2. The VA TBI second-level screen \[TBI event history and Neurobehavioral Symptom Inventory (NSI) for cognitive symptoms\].30 * To be eligible for enrollment in the randomized controlled, veterans at second-level screening must: 1. Meet threshold criteria for current full or sub-syndromal PTSD by DSM-IV criteria 31 2. Report ≥ 1 moderate or severe cognitive symptom(s) on the NSI that interfere(s) with daily function including moderate to severe poor concentration, forgetfulness, difficulty making decisions and slowed thinking. * Because PTSD is a highly comorbid condition, eligible participants may have other comorbid stable neuropsychiatric disorders, including depression or a history of a mild traumatic brain injury.
Exclusion criteria
* The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | 6-month follow-up | We presented change scores (6-month scores minus baseline scores) outcomes of 10 measures of neurocognitive measures (together with ranges): the Wechsler Memory Scale (WMS-IV) Paired Associates immediate and delayed memory (range: 1-19), Rey Auditory Verbal Learning Test (RAVLT) total score (range: 0-100) and delayed score (range: 0-20), Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span (range: 0-48), Wechsler Adult Intelligence Scale (WAIS-IV) Letter Number Sequencing (range: 1-19), Auditory Consonant Trigrams (ACT) raw score (range: 0-60), Delis-Kaplan Executive Function System (D-KEFS) Stroop Inhibition (range: 1-19), and the Brief Visual Memory Test revised (BVMT-R) total T score and Delayed T score (range: 20-80). Higher scores mean better cognitive functioning outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Social and Occupational Functioning and Quality of Life Scores at 6 Months | 6 month follow-up | To measure social and occupational functioning, we used the World Health Organisation Quality of Life Assessment (WHOQOL-BREF) validated to detect intervention-related change in quality of life. Range of post-treatment domain scores: WHOQOL physical domain: 7-35; WHOQOL psychological domain: 6-30; WHOQOL social relationships domain: 2-10; WHOQOL environment domain: 8-40. Higher scores indicate better quality of life outcomes. |
Countries
United States
Participant flow
Recruitment details
Recruitment flyers were posted on poster boards and electronic billboards around the SFVAMC; collaborated with other investigators to refer potential participants; utilized social media and created a website. We targeted community-based VA facilities, other Veteran community based organizations and local colleges and universities.
Participants by arm
| Arm | Count |
|---|---|
| Cognitive Training Plasticity Based Adaptive Cognitive Remediation (PACR)
Cognitive Training: Plasticity Based Adaptive Cognitive Remediation (PACR) | 25 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | failed inclusion criteria | 2 |
Baseline characteristics
| Characteristic | Cognitive Training |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 32.73 years STANDARD_DEVIATION 6.91 |
| Region of Enrollment United States | 25 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 25 |
| serious Total, serious adverse events | 0 / 25 |
Outcome results
Primary
Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention)
We presented change scores (6-month scores minus baseline scores) outcomes of 10 measures of neurocognitive measures (together with ranges): the Wechsler Memory Scale (WMS-IV) Paired Associates immediate and delayed memory (range: 1-19), Rey Auditory Verbal Learning Test (RAVLT) total score (range: 0-100) and delayed score (range: 0-20), Wechsler Adult Intelligence Scale (WAIS-IV) Digit Span (range: 0-48), Wechsler Adult Intelligence Scale (WAIS-IV) Letter Number Sequencing (range: 1-19), Auditory Consonant Trigrams (ACT) raw score (range: 0-60), Delis-Kaplan Executive Function System (D-KEFS) Stroop Inhibition (range: 1-19), and the Brief Visual Memory Test revised (BVMT-R) total T score and Delayed T score (range: 20-80). Higher scores mean better cognitive functioning outcomes.
Time frame: 6-month follow-up
Population: Challenges in recruitment/retention led us to redesign the study as an open trial and the limitation is that there is a small number of subjects who completed the study.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | WMS-IV Paired Associates Scaled score | 2.29 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | WMS-IV Paired Associates Delayed Scaled score | 2.29 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | RAVLT Total raw score | 0.71 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | RAVLT Delayed raw score | 0.14 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | WMS-IV Digit Span Scaled score | 2.43 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | WMS-IV Letter Number Sequencing scaled score | 0.286 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | ACT Raw score | 10.57 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | D-KEFS Stroop Inhibition Standard score | 2.71 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | BVMT Total T score | 0.71 score on a scale |
| Treatment | Change Scores of Standard (Untrained) Neurocognitive Measures (Verbal Memory, Learning and Sustained Attention) | BVMT Delayed T score | 7 score on a scale |
Secondary
Social and Occupational Functioning and Quality of Life Scores at 6 Months
To measure social and occupational functioning, we used the World Health Organisation Quality of Life Assessment (WHOQOL-BREF) validated to detect intervention-related change in quality of life. Range of post-treatment domain scores: WHOQOL physical domain: 7-35; WHOQOL psychological domain: 6-30; WHOQOL social relationships domain: 2-10; WHOQOL environment domain: 8-40. Higher scores indicate better quality of life outcomes.
Time frame: 6 month follow-up
Population: Challenges in recruitment/retention led us to redesign the study as an open trial and the limitation is that there is a small number of subjects who completed the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment | Social and Occupational Functioning and Quality of Life Scores at 6 Months | WHOQOL physical domain score | 12.65 score on a scale | Standard Deviation 2.75 |
| Treatment | Social and Occupational Functioning and Quality of Life Scores at 6 Months | WHOQOL psychological domain score | 10.10 score on a scale | Standard Deviation 2.29 |
| Treatment | Social and Occupational Functioning and Quality of Life Scores at 6 Months | WHOQOL social relationships domain score | 12.76 score on a scale | Standard Deviation 3.16 |
| Treatment | Social and Occupational Functioning and Quality of Life Scores at 6 Months | WHOQOL environment domain score | 14.00 score on a scale | Standard Deviation 2.75 |