Impact of Alcohol Use, Traumatic Stress, and Cigarette Smoking on Cognitive Functioning in Veterans With Co-occurring Alcohol Use Disorder and Posttraumatic Stress Disorder

IntroductionAlcohol use disorder (AUD) and PTSD have high rates of co-occurrence in U.S. Military Veterans resulting in incrementally worse functional outcomes relative to having either one of these disorders alone. Cognitive dysfunction can impede one's ability to benefit from standard behavioral AUD and PTSD treatments. Cigarette smoking is also highly prevalent among U.S. Military Veterans, and cognitive dysfunction is associated with chronic cigarette use among individuals with AUD and PTSD independently. However, much less is known about to what extent cigarette smoking further impairs cognitive functioning in individuals with both co-occurring AUD and PTSD.Materials and methodsU.S. Veterans with co-occurring AUD and PTSD (n = 162) completed a comprehensive cognitive assessment covering various domains: working memory, processing speed, mental switching, cognitive inhibition, auditory-verbal learning, auditory-verbal memory, and verbal fluency. To examine the impact of alcohol use, traumatic stress, and cigarette smoking on cognitive function, we conducted a three-way interaction examining the moderated effects of smoking status on the association between alcohol use and PTSD symptoms on a composite domain of global cognition.ResultsSmoking status in Veterans with co-occurring AUD and PTSD moderated the relationship between alcohol use and global cognition (P = .042), such that higher levels of alcohol use in the past week were related to worse global cognitive function among Veterans cigarette smokers (P = .015) but not among nonsmokers (P = .833). On follow-up analyses of individual cognitive domains, greater alcohol use in the past week was associated with lower cognitive inhibition in smokers but not nonsmokers, with traumatic stress symptoms moderating this effect (P = .039). Additionally, smoking status moderated the relationship between alcohol use and auditory-verbal learning, such that there was a differential relationship between alcohol use and auditory-verbal learning between smokers and nonsmokers.ConclusionsOverall, results provide evidence for the compounding impact of alcohol use, traumatic stress, and cigarette smoking on cognitive functioning. Impaired cognitive performance on a global level as well as on individual domains of cognitive inhibition and auditory-verbal learning were evident. Cognitive dysfunction may impede a Veteran's ability to benefit from therapeutic treatment, and these cognitive domains may represent potential targets for cognitive training efforts. Further, study results support smoking cessation initiatives and smoke-free policies enacted at Veterans Affairs healthcare facilities and medical centers

The Impact of Exercise and Virtual Reality Executive Function Training on Cognition Among Heavy Drinking Veterans With Traumatic Brain Injury: A Pilot Feasibility Study.

Executive function (EF) underlies self-control deficits in alcohol use disorder (AUD) and traumatic brain injury (TBI). Cognitive training is a promising adjunctive treatment targeting TBI- and AUD- related cognitive dysfunction. However, major limitations related to compliance and generalizability in the field of cognitive training exist. Physical activity is associated with enhanced cognitive performance across several executive functions and may enhance the benefits of cognitive training. Virtual reality provides multisensory embodied experiences which are likely to engage brain networks more efficiently than standard cognitive training systems, ultimately resulting in greater near- and far-transfer effects. This pilot study aimed to obtain feasibility data and a preliminary assessment of an enriched virtual reality (VR) EF training (EFT) intervention combined with exercise (NCT03786276). Using an 8-week randomized adaptive design study, 30 AUD treatment seeking U.S. Veterans completed nine sessions of exercise-only (n = 15) or gameplay control (n = 15) over 3 weeks, followed by a week-4 repeat assessment in Phase 1. Twenty-three participants completed and moved onto Phase II, where they completed up to nine sessions of VR-EFT plus exercise and completed a week-8 end-of-study assessment. Primary outcomes included feasibility to retain participants, usability, and satisfaction of using VR-EFT. Secondary and exploratory outcomes included within group assessment of change in cognitive function, alcohol use, alcohol craving, and post-concussive symptoms among the three treatment conditions.VR-EFT was feasible with moderate usability and high acceptability ratings.The most common VR-related adverse effect was motion sickness (n = 2/16, 12.5%). The VR-EFT condition was associated with significant improvement in inhibition-switching and visual scanning (both p < 0.05) during Phase II. Exercise-only was associated with significant improvements in cognitive inhibition, cognitive flexibility, reductions in alcohol craving, and number of standard alcohol drinks per week (all p ≤ 0.05). The gaming-control condition was associated with improvement in cognitive flexibility and visuospatial immediate recall (both p < 0.05) during Phase 1. Recruitment and retention of U.S. veterans with AUD and TBI into an exercise plus VR-EFT intervention is feasible, but technological barriers may impact usability. VR-EFT was associated with improvement in executive function domains that were targeted in as little as 3-week and nine sessions of VR-EFT exposure. Results are promising and indicate the need for a larger controlled investigation to assess the efficacy of VR-EFT to enhance treatment outcomes among AUD treatment-seeking U.S. veterans with co-occurring AUD and TBI.Clinical trial registrationwww.ClinicalTrials.gov, Identifier: NCT03786276

Alcohol use biomarkers predicting cognitive performance: a secondary analysis in veterans with alcohol dependence and posttraumatic stress disorder.

ObjectiveWe conducted a secondary analysis of baseline data from a recently completed pharmacological pilot clinical trial among 30 veterans with alcohol dependence and posttraumatic stress disorder (PTSD). This trial included baseline measures of alcohol use biomarkers, both indirect (carbohydrate-deficient transferrin, GGT [γ-glutamyltransferase], mean corpuscular volume, AST [aspartate aminotransferase], alanine aminotransferase) and direct (ethyl glucuronide, ethyl sulfate), as well as neurocognitive measures (Trail Making Test parts A and B, Hopkins Verbal Learning Test-Revised, Balloon Analogue Risk Task, Delay Discounting Task).MethodsTwo regression models were estimated and tested for each neurocognitive measure (dependent measure). The first model included the alcohol use biomarker alone as the predictor. The second model included the alcohol use biomarker along with the following 3 additional predictors: Beck Depression Inventory, Clinician-Administered PTSD Scale, and receiving medications.ResultsIn both models, the indirect biomarkers, such as GGT and AST, significantly predicted performance on the Hopkins Verbal Learning Test-Revised %Retention. GGT alone significantly predicted performance on the Trail Making Test part A.ConclusionsIndirect alcohol use biomarkers may have a specific role in identifying those veterans with alcohol dependence and PTSD who have impaired cognitive performance. However, direct alcohol use biomarkers may not share such a role

Alcohol Use Biomarkers Predicting Cognitive Performance: A Secondary Analysis in Veterans With Alcohol Dependence and Posttraumatic Stress Disorder

OBJECTIVE: We conducted a secondary analysis of baseline data from a recently completed pharmacological pilot clinical trial among 30 veterans with alcohol dependence and posttraumatic stress disorder (PTSD). This trial included baseline measures of alcohol use biomarkers, both indirect (carbohydrate-deficient transferrin, GGT [γ-glutamyltransferase], mean corpuscular volume, AST [aspartate aminotransferase], alanine aminotransferase) and direct (ethyl glucuronide, ethyl sulfate), as well as neurocognitive measures (Trail Making Test parts A and B, Hopkins Verbal Learning Test—Revised, Balloon Analogue Risk Task, Delay Discounting Task). METHODS: Two regression models were estimated and tested for each neurocognitive measure (dependent measure). The first model included the alcohol use biomarker alone as the predictor. The second model included the alcohol use biomarker along with the following 3 additional predictors: Beck Depression Inventory, Clinician-Administered PTSD Scale, and receiving medications. RESULTS: In both models, the indirect biomarkers, such as GGT and AST, significantly predicted performance on the Hopkins Verbal Learning Test—Revised %Retention. GGT alone significantly predicted performance on the Trail Making Test part A. CONCLUSIONS: Indirect alcohol use biomarkers may have a specific role in identifying those veterans with alcohol dependence and PTSD who have impaired cognitive performance. However, direct alcohol use biomarkers may not share such a role

Relationship of Age to Impulsivity and Decision Making: A Baseline Secondary Analysis of a Behavioral Treatment Study in Stimulant Use Disorders

Because stimulant use disorders remain prevalent across the lifespan, cognition is an important area of clinical care and research focus among aging adults with stimulant use disorders. This secondary analysis of a National Institute on Drug Abuse Clinical Trials Network study suggests that decision making, verbal learning/memory, executive function, and set shifting are important cognitive domains to screen clinically and treat in aging adults with stimulant use disorders. Some suggestions are made on how clinical treatment providers can practically use these results. An important direction for future research is the development of cognitively remediating treatments for impaired cognitive domains in aging adults with stimulant use disorders

A controlled trial of methadone treatment combined with directly observed isoniazid for tuberculosis prevention in injection drug users.

Substance abuse is associated with high risk for tuberculosis (TB) and poor adherence to medication regimens. This study compared completion rates for isoniazid (INH) preventive therapy for injection drug users (IDUs) randomly assigned to methadone treatment combined with directly observed preventive treatment (DOPT) versus those assigned to routine TB clinic referral without methadone treatment. One hundred and eleven opioid-dependent patients with latent TB were assigned to one of three 6-month treatment conditions: standard methadone treatment including substance abuse counseling combined with daily INH DOPT (n=37); minimal methadone treatment without counseling, also combined with daily INH DOPT (n=35); or routine care referral to TB clinic for monthly INH supplies without DOPT and without methadone treatment (n=39). INH completion rates were 77.1% for minimal methadone and 59.5% for standard methadone, as compared with only 13.5% for routine care (P<0.0001). Mean duration of INH treatment retention was 5.7, 5.0 and 1.6 months, respectively (P<0.0001). TB incidence at 4-year follow-up was 0 of 54 subjects who completed preventive therapy versus 2 of 57 who failed to complete. One of these two had been assigned to routine care, and the other to minimal methadone. In conclusion, INH retention time and completion rates were significantly improved by methadone treatment combined with observed INH, whether or not substance abuse counseling was provided. The results of this study indicate that methadone treatment offers clear public health benefits when it is used to deliver preventive medical services

A randomized pilot trial of topiramate for alcohol use disorder in veterans with traumatic brain injury: Effects on alcohol use, cognition, and post-concussive symptoms.

BackgroundTopiramate is an effective treatment for alcohol use disorder (AUD) and has also been used in the care of mild traumatic brain injury (mTBI). This pilot study aimed to obtain a preliminary assessment of topiramate's efficacy in reducing alcohol use and post-concussive symptoms, and its potential negative impact on cognitive function in 32 Veterans with co-occurring AUD and mTBI.MethodsThis was a prospective 12-week, randomized, double-blind, placebo-controlled pilot study of flexible-dose topiramate or placebo. Primary outcome was reduction of drinking days per week within the topiramate arm. Secondary outcomes included between group comparisons of alcohol use and craving, post-concussive symptoms, and cognitive function.ResultsDrinking days per week significantly decreased within both the topiramate and placebo arm. There were no significant treatment-by-week interactions on alcohol use/craving, or post-concussive symptoms in intent-to-treat analyses. In per-protocol analyses, topiramate significantly reduced number of drinks per week compared with placebo. Topiramate transiently impaired verbal fluency and working memory. Processing speed, cognitive inhibition, and mental flexibility significantly improved between weeks 1 and 12, regardless of treatment arm.ConclusionsSignificant improvement occurred in both the topiramate and placebo groups over 12 weeks of treatment in alcohol use and post-concussive symptoms. Among treatment completers there was greater reduction of alcohol use in the topiramate arm. Topiramate was also associated with negative but transient effects on cognitive function. Results suggest both a possible benefit for topiramate treatment in reducing alcohol use and some potential for negative cognitive effects in Veterans with AUD and mTBI