Mar 9, 2015 - This study will investigate both combat exposure and PTSD as factors that may .... trial verbal learning and memory test with documented.
ORIGINAL ARTICLES Authors alone are responsible for opinions expressed in the contribution and for its clearance through their federal health agency, if required.
MILITARY MEDICINE, 180, 3:285, 2015
Combat Exposure, PTSD Symptoms, and Cognition Following Blast-Related Traumatic Brain Injury in OEF/OIF/OND Service Members and Veterans Maya Troyanskaya, MD*†; Nicholas J. Pastorek, PhD*†; Randall S. Scheibel, PhD*†; Nancy J. Petersen, PhD*‡; Katie McCulloch, PhD*§; Elisabeth A. Wilde, PhD*†∥¶; Helene K. Henson, MD*†; Harvey S. Levin, PhD*†**††‡‡ ABSTRACT Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are frequently documented among the Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND) veterans. This study will investigate both combat exposure and PTSD as factors that may influence objective cognitive outcomes following blast-related mild TBI (mTBI). Participants included 54 OEF/OIF/OND veterans who had been exposed to blast and reported symptoms consistent with mTBI and 43 combat-deployed control participants who had no history of blast exposure or TBI. Raw scores from the Controlled Oral Word Association Test, Trail Making Test, Color-Word Interference Test, and Verbal Selective Reminding Test were used to measure cognitive functioning. All participants demonstrated adequate effort on the Word Memory Test. Demographics, injury characteristics, overall intellectual functioning, and total scores from the PTSD Checklist-Civilian Version (PCL-C) and Combat Exposure Scale (CES) were used as the predictors for each cognitive measure. History of mTBI was significantly associated with higher PCL-C and CES scores. Multivariable linear regression, however, showed no significant differences in cognitive performance between groups. The absence of effect of mTBI, PTSD, and combat exposure on cognitive functioning noted in this study may be partially explained by the inclusion of only those participants who passed performance validity testing.
INTRODUCTION Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are frequently documented among combat veterans *Michael E. DeBakey Veterans Affairs Medical Center, 2002 Holcombe Blvd, Houston, TX 77030. †Department of Physical Medicine and Rehabilitation, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. ‡Department of Medicine, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. §Department of Psychology, University of Houston, 126 Heyne Building Houston, TX 77204. kDepartment of Neurology, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. ¶Department of Radiology, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. **Department of Pediatrics, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. ††Department of Neurosurgery, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. ‡‡Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine 1 Baylor Plaza Houston, TX 77030. This article was presented in poster format at the International Neurological Society meeting, Seattle, Washington, DC, February 12–February15, 2014. doi: 10.7205/MILMED-D-14-00256
who were deployed as part of Operation Enduring Freedom/ Operation Iraqi Freedom/Operation New Dawn (OEF/OIF/OND). Head and neck injuries have been reported in one quarter of evacuated service members1 and, in one study of those returning from Iraq, approximately 15% reported a history of mild traumatic brain injury (mTBI). Thirty-three percent of these veterans also reported symptoms consistent with PSTD.2 The rates of the PTSD diagnosis increase with time during the first 12 months after returning from a combat zone.3,4 The disorder can persist for years after deployment and symptoms can worsen over time.5 Highly stressful combat theaters, multiple deployments, and the length of these deployments likely contribute to the elevated prevalence of PTSD. Mild TBI and PTSD may present as comorbid disorders, and many of the symptoms that veterans report are nonspecific complaints that are characteristic of both, such as memory and attention problems. In response, the Department of Defense and the Department of Veterans Affairs have implemented screenings to identify these conditions and have funded research to examine the etiology of symptoms in this population. The relation between deployment-related experiences and health outcomes appears to be quite complex. In examining the relation between a history of mTBI and the development
MILITARY MEDICINE, Vol. 180, March 2015 Downloaded from publications.amsus.org: AMSUS - Association of Military Surgeons of the U.S. IP: 152.131.009.069 on Mar 09, 2015. Copyright (c) Association of Military Surgeons of the U.S. All rights reserved.
285
Outcomes Following Blast-Related TBI in OEF/OIF/OND Service Members
of comorbid PTSD, Hoge et al2 found that those veterans who experience mTBI with loss of consciousness (LOC) are more likely to report poor health and subjective cognitive complaints than those who do not experience LOC. However, when PTSD is included within the model as a covariate, the only physical or cognitive symptom that remains associated with history of mTBI is headache. Alternatively, Vanderploeg et al6 has commented that PTSD may be more correctly classified as an outcome variable, as PTSD is inherently associated with a variety of symptoms that may overlap with these health outcomes. Amount of exposure to combat may help to explain the complex relation between mTBI history, PTSD, and health outcomes, given that combat exposure has been associated with greater risk of experiencing physical and psychological traumas.2,7 As of yet, there has been no consensus on how these variables are related. This study will investigate both combat exposure and PTSD as factors that may influence objective cognitive outcomes, such as memory and processing speed following mTBI in OEF/OIF/OND veterans.
METHODS Participants The study was approved by the institutional review board and all participants provided written informed consent before study enrollment. Ninety-seven OEF/OIF/OND service members and veterans who were deployed to Afghanistan or Iraq during recent conflicts were recruited through various clinics at a southern VA Medical Center and local veterans’ organizations. Fifty-four participants reported exposure to at least one primary blast and a history of LOC, confusion or disorientation, or post-traumatic amnesia (PTA) consistent with mTBI. Criteria for mTBI included LOC of 30 minutes or less, confusion or disorientation for more than 5 minutes but less than 24 hours, and PTA of less than 24 hours.8 Individuals who only reported a period of confusion or disorientation lasting less than 5 minutes after the blast were not enrolled in this study since a brief alteration of mental status may be better accounted for by “fog of war” rather than a brain injury.2 The 43 participants in the control group had no history of TBI or exposure to blast. None of the participants in either group had a history of severe neurological or psychiatric disorder (e.g., schizophrenia or bipolar disorder), pre- or postdeployment TBI, learning disability, dyslexia, or current alcohol or drug abuse problems. All study participants were English speakers. Screening Measures The Alcohol Use Disorders Identification Test (AUDIT) was used to screen for ongoing alcohol abuse.9 The AUDIT contains 10 multiple-choice questions on quantity and frequency of alcohol consumption, drinking behavior, and alcohol-related problems. The Drug Abuse Screening Test (DAST-10) was used to screen for ongoing drug use.10 The DAST-10 contains 10 yes/no questions concerning information about possible involvement with drugs, not including alcoholic beverages, during the past 12 months. Total scores were used for both 286
AUDIT (cut-off score £ 8) and DAST-10 (cut-off score < 3). All participants also completed the Combat Exposure Scale (CES) and PTSD Checklist–Civilian (PCL-C). The CES is a self-report measure containing 7 multiple-choice questions that assesses war zone-related stressors experienced by military personnel.11 The total score ranges from 0 to 41 and can be classified within 1 of 5 categories ranging from “light” to “heavy.” The PCL-C is a brief self-report symptom inventory of 17 PTSD symptoms, which are rated on a 5-point scale of severity based on the past month and it does not assume that all traumatic experiences are related to combat.12 The 17 items of the PCL-C directly reflect the symptoms represented in the DSM-IV-TR diagnostic criteria for PTSD,13 with scores that range from 17 to 85. The Word Memory Test (WMT) was used to assess effort.14 The WMT is a computerized symptom validity assessment instrument, which examines the immediate and delayed recognition of words following an initial presentation of 20 semantically related word pairs. A measure of response consistency across the immediate and delayed recognition conditions was also used. Evidence of adequate effort was defined by the recommended cutoff scores on all of the three primary effort subtests, and all participants included in this analysis performed above the cutoff scores. Ninety-six individuals with history of blast-related mTBI met study inclusion criteria described above, but 42 were ultimately excluded because of failure on the WMT. Only those participants who passed the WMT underwent neuropsychological testing and, thus, were included in this study. The Test of Nonverbal Intelligence (TONI) was used to assess current level of intellectual functioning.15 For this measure, the participants were asked to analyze spatial arrays and determine which of several shapes would most appropriately fit into a blank space. The TONI does not require any verbal communication and all responses are indicated with pointing. The Polytrauma Interview was used to assess deployment and injury-related information (e.g., number of deployments and the type, number, and proximity of blasts), and associated subjective LOC, disorientation, and PTA. This clinician-administered interview was adapted from the VA TBI secondary evaluation.16 In addition to deployment-related injury information, the Polytrauma Interview also collects data regarding preand postdeployment injury history. This instrument was used to establish the TBI history and severity. Basic demographic information were also collected.
Neuropsychological Measures The Verbal Selective Reminding Test (VSRT)17 is a multipletrial verbal learning and memory test with documented sensitivity to memory dysfunction in civilian mTBI populations. The VSRT consists of a list of 12 words, which the examiner reads to the participant. The participant is then asked to recall as many of these words as possible. After each trial, the examiner selectively presents only words that were omitted during the preceding trial. A delayed recall trial was given 30 minutes later, and the participant was asked again to recall as many words as possible. The six-trial version of the test was used18 and three measures were calculated: (1) total MILITARY MEDICINE, Vol. 180, March 2015
Downloaded from publications.amsus.org: AMSUS - Association of Military Surgeons of the U.S. IP: 152.131.009.069 on Mar 09, 2015. Copyright (c) Association of Military Surgeons of the U.S. All rights reserved.
Outcomes Following Blast-Related TBI in OEF/OIF/OND Service Members
consistent long-term retrieval (CLTR) across all six trials, (2) total number of correctly recalled words across all six trials, and (3) 30-minute delayed recall: the number of words recalled 30 minutes after initial test administration. The Controlled Oral Word Association Test was used to assess verbal fluency,19 and, during this test, participants were asked to name as many words as possible starting with a provided letter within 60-second intervals. The total number of correct words across three trials was used. The Trail Making Test (TMT) was used to assess visual attention and task switching capabilities.20 For part A (TMT-A), the participants were instructed to connect a set of 25 numbered circles in order. During part B (TMT-B), the participants were instructed to connect a set of 25 circles containing numbers and letters in alternating, ascending order. Total completion times in seconds were used. The Delis–Kaplan Executive Function System Color-Word Interference Test (CWIT) was used to assess inhibition and inhibition/switching.21 For the inhibition measure, participants named the ink color of an incongruent color word. The inhibition/switching subtest was similar, except that the instruction for naming the ink color or reading the word was dependent on whether or not the printed word was surrounded by a box. The completion times in seconds were used for both subtests of the CWIT.
Statistical Analyses To compare the demographic characteristics, cognitive performance, and PCL-C and CES total scores between the control and mTBI groups, t tests were used. Multivariable ordinary least squares linear regression was used to determine the relation between demographic and clinical characteristics and group status on cognitive performance. Specifically, the participants’ demographic and deployment-related characteristics (i.e., age, education, time since last deployment, and TONI) were included in each model as control variables. Group status, categorized into mTBI or control, and the CES were entered as the predictor variables, simultaneously with the demographic characteristics. Although a stepwise entry method may have resulted in fewer variables being included in the final models and thus increased power to detect relations between the remaining variables, the simultaneous entry method was felt to better answer questions about the relative contribution of various demographic and clinical characteristics on cognitive outcomes. The full model was alternatively built with the TABLE I.
PCL-C, instead of the CES, to determine the relative impact of current post-traumatic stress symptoms versus historical ratings of combat exposure on cognition. These full models were run separately for each of the eight dependent variables of cognitive functioning examined in this study. p-Values of 0.05 or less were considered statistically significant. The multiple R2 value, representing the proportion of variance in the dependent variable attributable to the independent variables, was provided for each model.
RESULTS The participants with history of mTBI who passed and those who failed the WMT did not differ significantly in age, education, postdeployment interval, or level of combat exposure. Forty-two individuals who failed the WMT reported much higher level of the current PTSD symptoms ( p < 0.0001). As described previously, those participants failing the WMT were excluded from the remainder of the analyses. Participants with and without a history of blast-related mTBI did not differ significantly in age, education, postdeployment interval, or current level of intellectual functioning (Table I). Significant group differences were found on CES and PCL-C total scores (Table I). The regression analyses including age, education, time since last deployment, TONI, the CES or PTSD, and TBI group status as the predictor variables revealed a significant effect of age on the completion time for the TMT-A ( p = 0.002) and CWIT ( p = 0.014) and the total number of words recalled on the VRST ( p = 0.04), with increasing age negatively affecting performance on the cognitive measures (i.e., slower completion time on TMT-A and CWIT and fewer words recalled on the VSRT). Despite heavier combat exposure and greater endorsement of the PTSD symptoms by the participants in TBI group, there was no significant effect of history of mTBI, greater combat exposure, or severity of PTSD symptoms on cognitive performance (Table II). DISCUSSION Despite significant between-group differences in intensity of combat exposure and severity of current post-traumatic stress symptoms, there were no differences in performance on cognitive measures of processing speed, memory, and executive functioning. This was possibly due to the use of the
Demographic Characteristics, Deployment-Related Characteristics, and Current PTSD Symptoms of mTBI and Control Groups mTBI (N = 54)
Age (Years) Education (Years) TONI Index Score Post-Deployment Interval to Test (Years) CES Total Score PCL-C Total Score
Control (N = 43)
Mean
SD
Mean
SD
p Valuea
32.1 13.8 101.4 4.5 22.7 43.9
6.5 12.5 8.9 1.8 7.7 14.9
31.3 14.4 99.9 4.5 5.1 25.9
6.3 1.9 8.7 2.3 5.8 10.2
0.57 0.18 0.43 0.97
