Executive dysfunction, including working memory deficits, is prominent in posttraumatic stress disorder (PTSD) and can impede treatment effectiveness. Intervention approaches that target executive dysfunction alongside standard PTSD treatments could boost clinical response. The current study reports secondary analyses from a randomized controlled trial testing combined PTSD treatment with a computerized training program to improve executive dysfunction. We assessed if pre-treatment neurocognitive substrates of executive functioning predicted clinical response to this novel intervention.

Treatment-seeking veterans with PTSD (N = 60) completed a working memory task during functional magnetic resonance imaging prior to being randomized to six weeks of computerized executive function training (five 30-minute sessions each week) plus twelve 50-minute sessions of cognitive processing therapy (CEFT + CPT) or placebo training plus CPT (PT + CPT). Using linear mixed effects models, we examined the extent to which the neurocognitive substrates of executive functioning predicted PTSD treatment response.

Results indicated that veterans with greater activation of working memory regions (e.g. lateral prefrontal and cingulate cortex) had better PTSD symptom improvement trajectories in CEFT + CPT v. PT + CPT. Those with less neural activation during working memory showed similar trajectories of PTSD symptom change regardless of treatment condition.

Greater activity of frontal regions implicated in working memory may serve as a biomarker of response to a novel treatment in veterans with PTSD. Individuals with greater regional responsiveness benefited more from treatment that targeted cognitive dysfunction than treatment that did not include active cognitive training. Clinically, findings could inform our understanding of treatment mechanisms and may contribute to better personalization of treatment.

Illness perception, or the ways in which individuals understand and cope with injury, has been extensively studied in the broader medical literature and has been found to have important associations with clinical outcomes across a wide range of medical conditions. However, there is a dearth of knowledge regarding how perceptions of traumatic brain injury (TBI) influence outcome and recovery following injury, especially in military populations. The purpose of this study was to examine relationships between illness perception, as measured via symptom attribution, and neurobehavioral and neurocognitive outcomes in Veterans with TBI history.

This cross-sectional study included 44 treatment-seeking Veterans (86.4% male, 65.9% white) with remote history of TBI (75.0% mild TBI). All Veterans were referred to the TBI Cognitive Rehabilitation Clinic at VA San Diego and completed a clinical interview, self-report questionnaires, and a neuropsychological assessment. A modified version of the Neurobehavioral Symptom Inventory (NSI) was administered to assess neurobehavioral symptom endorsement and symptom attribution. Symptom attribution was assessed by having participants rate whether they believe each NSI item was caused by TBI. A total symptom attribution score was computed, as well as the standard NSI total and symptom cluster scores (i.e., vestibular, somatic, cognitive, and affective symptom domains). Three cognitive composite scores (representing mean performance) were also computed, including memory, attention/processing speed, and executive functioning. Participants were excluded if they did not complete the NSI attribution questions or they failed performance validity testing.

Results showed that the symptoms most frequently attributed to TBI included forgetfulness (82%), poor concentration (80%), and slowed thinking (77%). There was a significant positive association between symptom attribution and the NSI total score (r = 0.62, p < .001), meaning that greater attribution of symptoms to TBI was significantly associated with greater symptom endorsement overall.

Symptom attribution was also significantly associated with all four NSI symptom domains (r’s = 0.47-0.66; all p’s < .001), with the strongest relationship emerging between symptom attribution and vestibular symptoms. Finally, linear regressions demonstrated that symptom attribution but not symptom endorsement was significantly associated with objective cognitive functioning. Specifically, greater attribution of symptoms to TBI was associated with worse memory (ß = -0.33, p = .035) and attention/processing speed (ß = -0.40, p = .013) performance.

Results showed significant associations between symptom attribution and (1) symptom endorsement and (2) objective cognitive performance in Veterans with a remote history of TBI. Taken together, findings suggest that Veterans who attribute neurobehavioral symptoms to their TBI are at greater risk of experiencing poor long-term outcomes. Although more research is needed to understand how illness perception influences outcomes in this population, results highlight the importance of early psychoeducation regarding the anticipated course of recovery following TBI.

Practice effects (PE) on cognitive testing impede our ability to accurately assess change. In particular, they hamper the detection of mild cognitive impairment (MCI) and progression to dementia by delaying the point at which test scores fall below diagnostic impairment cutoffs. When decline over time is expected, as with older adults or progressive diseases, failure to adequately address PEs may lead to inaccurate conclusions because PEs artificially boost scores while pathology-related or age-related decline reduces scores. The participant-replacement method accounts for PEs by comparing performance of demographically-matched replacement participants to returnees who have been tested previously. Unlike most methods, the participant-replacement method can separate pathology- or age-related decline from PEs; however, this method has only been used across two timepoints. Neuropsychologists tend to think that PEs level out after the first follow-up, but this issue has not been evaluated in models that allow PEs in the presence of overall decline. Including more than two timepoints makes it possible to determine if PEs level out after the first follow-up, but it is analytically challenging because individuals may not be assessed at every timepoint.

We examined 1190 older adults in the Alzheimer’s Disease Neuroimaging Initiative who were cognitively unimpaired (n=809) or had MCI (n=381) at baseline. Participants completed six neuropsychological measures (Trails A, Trials B, Boston Naming Test, Category Fluency, Logical Memory, Rey Auditory Verbal Learning Task) at three timepoints (baseline, 12-month, 24-month). We implemented the participant-replacement method using generalized estimating equations in comparisons of matched returnees and replacements to calculate PEs. Propensity scores matched individuals on age, education, sex, and an estimate of premorbid functioning. Generalized estimating equations modeled PEs and age-related decline separately for each cognitive measure.

We observed significant PEs for 5 of the 6 measures in the cognitively unimpaired group and 4 measures in the baseline MCI group. PEs did not uniformly decrease across time; some—specifically on episodic memory measures—continued to increase beyond the first follow-up for both groups of participants. Without accounting for PEs, cognitive function appeared to improve or stay the same. In contrast, when PEs were included in the models, cognitive function appeared to decline or stay the same across time.

The replacement method of PE adjustment revealed significant PEs across two follow-ups. PEs for episodic memory, in particular, did not level out, but actually increased after the first follow-up, two years after baseline. As expected in these older adults, accounting for PEs revealed cognitive decline, in some cases, even when PE-unadjusted scores improved. This method of assessing PEs, in turn, means earlier detection of cognitive deficits, including progression to MCI, and more accurate characterization of longitudinal change.

Mild traumatic brain injury (mTBI), depression, and posttraumatic stress disorder (PTSD) are a notable triad in Operation Enduring Freedom, Operation Iraqi Freedom, and Operation New Dawn (OEF/OIF/OND) Veterans. With the comorbidity of depression and PTSD in Veterans with mTBI histories, and their role in exacerbating cognitive and emotional dysfunction, interventions addressing cognitive and psychiatric functioning are critical. Compensatory Cognitive Training (CCT) is associated with improvements in areas such as prospective memory, attention, and executive functioning and has also yielded small-to-medium treatment effects on PTSD and depressive symptom severity. Identifying predictors of psychiatric symptom change following CCT would further inform the interventional approach. We sought to examine neuropsychological predictors of PTSD and depressive symptom improvement in Veterans with a history of mTBI who received CCT.

37 OEF/OIF/OND Veterans with mTBI history and cognitive complaints received 10-weekly 120-minute CCT group sessions as part of a clinical trial. Participants completed a baseline neuropsychological assessment including tests of premorbid functioning, attention/working memory, processing speed, verbal learning/memory, and executive functioning, and completed psychiatric symptom measures (PTSD Checklist-Military Version; Beck Depression Inventory-II) at baseline, post-treatment, and 5-week follow-up. Paired samples t-tests were used to examine statistically significant change in PTSD (total and symptom cluster scores) and depressive symptom scores over time. Pearson correlations were calculated between neuropsychological scores and PTSD and depressive symptom change scores at post-treatment and follow-up. Neuropsychological measures identified as significantly correlated with psychiatric symptom change scores (p^.05) were entered as independent variables in separate multiple linear regression analyses to predict symptom change at post-treatment and follow-up.

Over 50% of CCT participants had clinically meaningful improvement in depressive symptoms (>17.5% score reduction) and over 20% had clinically meaningful improvement in PTSD symptoms (>10-point improvement) at post-treatment and follow-up. Examination of PTSD symptom cluster scores (re-experiencing, avoidance/numbing, and arousal) revealed a statistically significant improvement in avoidance/numbing at follow-up. Bivariate correlations indicated that worse baseline performance on D-KEFS Category Fluency was moderately associated with PTSD symptom improvement at post-treatment. Worse performance on both D-KEFS Category Fluency and Category Switching Accuracy was associated with improvement in depressive symptoms at post-treatment and follow-up. Worse performance on D-KEFS Trail Making Test Switching was associated with improvement in depressive symptoms at follow-up. Subsequent regression analyses revealed worse processing speed and worse aspects of executive functioning at baseline significantly predicted depressive symptom improvement at post-treatment and follow-up.

Worse baseline performances on tests of processing speed and aspects of executive functioning were significantly associated with improvements in PTSD and depressive symptoms during the trial. Our results suggest that cognitive training may bolster skills that are helpful for PTSD and depressive symptom reduction and that those with worse baseline functioning may benefit more from treatment because they have more room to improve. Although CCT is not a primary treatment for PTSD or depressive symptoms, our results support consideration of including CCT in hybrid treatment approaches. Further research should examine these relationships in larger samples.

Clarifying the relationship between depression symptoms and cardiometabolic and related health could clarify risk factors and treatment targets. The objective of this study was to assess whether depression symptoms in midlife are associated with the subsequent onset of cardiometabolic health problems.

The study sample comprised 787 male twin veterans with polygenic risk score data who participated in the Harvard Twin Study of Substance Abuse (‘baseline’) and the longitudinal Vietnam Era Twin Study of Aging (‘follow-up’). Depression symptoms were assessed at baseline [mean age 41.42 years (s.d. = 2.34)] using the Diagnostic Interview Schedule, Version III, Revised. The onset of eight cardiometabolic conditions (atrial fibrillation, diabetes, erectile dysfunction, hypercholesterolemia, hypertension, myocardial infarction, sleep apnea, and stroke) was assessed via self-reported doctor diagnosis at follow-up [mean age 67.59 years (s.d. = 2.41)].

Total depression symptoms were longitudinally associated with incident diabetes (OR 1.29, 95% CI 1.07–1.57), erectile dysfunction (OR 1.32, 95% CI 1.10–1.59), hypercholesterolemia (OR 1.26, 95% CI 1.04–1.53), and sleep apnea (OR 1.40, 95% CI 1.13–1.74) over 27 years after controlling for age, alcohol consumption, smoking, body mass index, C-reactive protein, and polygenic risk for specific health conditions. In sensitivity analyses that excluded somatic depression symptoms, only the association with sleep apnea remained significant (OR 1.32, 95% CI 1.09–1.60).

A history of depression symptoms by early midlife is associated with an elevated risk for subsequent development of several self-reported health conditions. When isolated, non-somatic depression symptoms are associated with incident self-reported sleep apnea. Depression symptom history may be a predictor or marker of cardiometabolic risk over decades.

Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.

Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).

Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.

Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.