Explore the vast range of titles available.

Objective:Many Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans have sustained a mild traumatic brain injury (mTBI) during their military service and a substantial “miserable minority” frequently report significant cognitive complaints long after injury. Although existing studies have shown associations between genetic factors (e.g., apolipoprotein E [APOE] and brain-derived neurotrophic factor [BDNF]) and cognitive performance in this vulnerable population, the TBI-genetics literature has generally been varied and inconsistent. Although past findings suggest that individuals who possess APOE £4 and BDNF Met alleles have worse cognitive outcomes after mTBI, this has not been consistently reported. Additionally, the influence of any gene-by-gene interactions on cognition has not been sufficiently explored and therefore remains a critical area of interest. Thus, we examined relationships between APOE and BDNF genotypes on neuropsychological function in a well-characterized sample of younger Veterans with mTBI histories.Participants and Methods:Participants included Veterans with a history of mTBI who adequately completed performance validity testing. In total, 78 Veterans (84.6% male; age: M=32.95, SD=7.00; race/ethnicity: 51.3% White, 28.2% Hispanic/Latino, and 20.5% Another Race/Ethnicity) completed a structured clinical interview to collect detailed information on TBI history and underwent a comprehensive neuropsychological exam. A buccal swab was also collected to determine APOE and BDNF allele status for each participant. Three cognitive composite scores were computed reflecting memory (8 items), attention/processing speed (7 items), and executive functioning (10 items). Two-way analyses of covariance (ANCOVAs) adjusting for age, sex, and race/ethnicity were used to assess the effects of APOE (ε4+ vs. ε4-) and BDNF (Met+ vs. Met-) on cognitive functioning (ε4+/Met-: n=12, ε4+/Met+: n=8, £4-/Met-: n=35, and ε4-/Met+: n=23).Results:ANCOVAs revealed no significant main effects for APOE or BDNF genotypes on cognitive functioning; however, there was a significant APOE x BDNF genotype interaction for all three cognitive composites (memory: p=.026, np2=.068; attention/processing speed: p=.045, np2=.055; and executive functioning: p=.031, np2=.064). Specifically, the interaction was such that Veterans in the ε4+/Met+ group demonstrated the poorest cognitive functioning relative to all other allele group combinations (ε4+/Met-, ε4-/Met+, ε4-/Met-).Conclusions:The results of this preliminary study demonstrate that, compared to the other genetic subgroups in the TBI sample, Veterans with APOE £4 and BDNF Met alleles demonstrated the poorest cognitive functioning across several domains known to be negatively affected in the context of head injury (i.e., memory, attention/processing speed, and executive functioning). These findings are the first to show an APOE x BDNF interaction in Veterans with histories of mTBI. Furtherresearch is necessary to replicate and extend this study in larger samples. Moreover, future work should incorporate neuroimaging variables to better interrogate structural and functional correlates of these observed genetic polymorphism associations in Veterans with mTBI histories.

Post-traumatic stress disorder (PTSD) and hypertension are highly prevalent among Veterans. Cognitive dispersion, indicating within-person variability across neuropsychological measures at one time point, is associated with increased risk of dementia. We examined interactive effects of PTSD symptom severity and hypertension on cognitive dispersion among older Veterans. We included 128 Vietnam-era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (DoD-ADNI) with a history of PTSD. Regression models examined interactions between PTSD symptom severity and hypertension on cognitive dispersion (defined as the intraindividual standard deviation across eight cognitive measures) adjusting for demographics and comorbid vascular risk factors. There was an interaction between PTSD symptom severity and hypertension on cognitive dispersion ( = .026) but not on mean cognitive performance ( = .543). Greater PTSD symptom severity was associated with higher cognitive dispersion among those with hypertension ( = .002), but not among those without hypertension ( = .531). Results remained similar after adjusting for mean cognitive performance. Findings suggest, among older Veterans with PTSD, those with both hypertension and more severe PTSD symptoms may be at greater risk for cognitive difficulties. Further, cognitive dispersion may be a useful marker of subtle cognitive difficulties. Future research should examine these associations longitudinally and in a diverse sample.

Abstract Both post-traumatic stress disorder (PTSD) and traumatic brain injury (TBI) have been linked to subjective cognitive complaints; however, less is known about the unique relationships of PTSD symptoms and TBI severity with domain-specific subjective cognitive declines in older Veterans. The current study included 215 Vietnam-Era Veterans from the Department of Defense-Alzheimer's Disease Neuroimaging Initiative (age M=69.62 years, SD=4.30). General linear models, adjusting for age, education, apolipoprotein E ε4 status, self-reported health, MMSE score, and depressive symptoms, examined the unique effects of PTSD symptoms (measured using the Clinician-Administered PTSD Scale) and TBI severity (none, mild, moderate/severe) on subjective cognitive decline measured using the Everyday Cognition (ECog) measure. Greater current PTSD symptoms were associated with greater subjective cognitive declines on the ECog total score (t=.198, p=.009) as well as memory (t=.197, p=.008), language (t=.228, p=.004), and visuospatial (t=.216, p=.007) subscales. Compared with participants with no TBI, mild TBI was associated with greater subjective cognitive decline on the ECog total score (t=.329, p=.026) as well as the language (t=.334, p=.030) and divided attention (t=.411, p=.007) subscales, while moderate-to-severe TBI was associated with greater subjective declines in planning (t=.291, p=.049) and divided attention (t=.320, p=.032). There was no interaction between PTSD and TBI severity on ECog scores. Results suggest that PTSD symptoms and mild versus moderate/severe TBI differentially impact specific domains of subjective cognitive decline. Future work should investigate how repetitive TBI may modify these relationships, and whether PTSD and TBI severity are associated with objective cognition and quality of life in older Veterans.