Prior Traumatic Brain Injury Research Articles

The Long-Term Sequelae of Traumatic Brain Injury over 10 Years of Follow-Up-a Matched Cohort Study Based on Routine Data of a German Statutory Health Insurance Carrier.

The acute effects of traumatic brain injury (TBI) are well documented, but there is no systematic quantification of its long-term sequelae in German-language literature. The purpose of this article is to compare the frequency of conditions linked to prior TBI with their frequency in the non-brain-injured population. A matched cohort study was carried out on the basis of routine data from the BARMER statutory health insurance carrier. The exposure group consisted of patients treated over the period 2006-2009 for TBI at a variety of treatment intensities, including persons with multiple organ trauma. The control group consisted of BARMER insurees without prior TBI who were matched with the patients in the exposure group for age, sex, and pre-existing diseases. Late sequelae were sought in the routine data for a period of ten years after the injury. The outcome rates of the exposure and control groups were compared with Kaplan-Meier estimators and Poisson regression. 114 296 persons with TBI in the period 2006-2009 were included in the study. The mortality within ten years of TBI was 305 per 1000 individuals. The relative mortality in the exposure group was higher than that in control individuals of the same age and sex, with an incidence rate ratio (IRR) of 1.67 (95% confidence interval, [1.60; 1.74]). Immobility, dementia, epilepsy, endocrine disorders, functional disorders, depression, anxiety, cognitive deficits, headache, and sleep disorders were also more common in the exposure group. Persons with TBI requiring high-intensity treatment displayed the highest relative incidence rates of the conditions studied over 10 years of follow-up. Persons who had been admitted to the hospital because of TBI had higher relative incidence rates for epilepsy and dementia than those who had been cared for on an outpatient basis. Adverse sequelae of TBI can still be seen ten years after the exposure. These patients die earlier than persons without TBI and suffer earlier and more frequently from associated conditions.

Care patterns and predictors of community residence among older patients after hospital discharge for traumatic brain injury.

An increasing number of older adults with traumatic brain injury (TBI) require hospitalization, but it is unknown whether they return to their community following discharge. We examined community residence following acute hospital discharge for TBI in Texas and identified factors associated with 90-day community residence and readmission. We conducted a retrospective cohort study using 100% Texas Medicare claims data of patients older than 65 years hospitalized for a TBI from January 1, 2014, through December 31, 2017, and followed for 20 weeks after discharge. Discharges to short-term and long-term acute hospital, inpatient rehabilitation facility (IRF), skilled nursing facility (SNF), long-term nursing home (NH), and hospice were identified. The primary outcome was 90-day community residence. Our secondary outcome was 90-day, all-cause readmission. In Texas, 26,985 Medicare fee-for-service patients were hospitalized for TBI (Racial and ethnic minorities: 21.1%; Females 57.3%). At 90 days and 20 weeks following discharge, 80% and 84% were living in the community respectively. Female sex (OR=1.16 [1.08-1.25]), Hispanic ethnicity (OR=2.01 [1.80-2.25]), "other" race (OR=2.19 [1.73-2.77]), and prior primary care provider (PCP; OR=1.51 [1.40-1.62]) were associated with increased likelihood of 90-day community residence. Patients aged 75+, prior NH residence, dual eligibility, prior TBI diagnosis, and moderate-to-severe injury severity were associated with decreased likelihood of 90-day community residence. Being non-Hispanic Black (HR=1.33 [1.20-1.46]), discharge to SNF (HR=1.56 [1.48-1.65]) or IRF (HR=1.49 [1.40-1.59]), having prior PCP (HR=1.23 [1.17-1.30]), dual eligibility (HR=1.11 [1.04-1.18]), and prior TBI diagnosis (HR=1.05 [1.01-1.10]) were associated with increased risk of 90-day readmission. Female sex and "other" race were associated with decreased risk of 90-day readmission. Most older adults with TBI return to the community following hospital discharge. Disparities exist in returning to the community and in risk of 90-day readmission following hospital discharge. Future studies should explore how having a PCP influences post-hospital outcomes in chronic care management of older patients with TBI.

Traumatic Brain Injury Associates with an Earlier Onset in Sporadic Frontotemporal Dementia.

Currently, there are few studies considering possible modifiable risk factors of frontotemporal dementia (FTD). In this retrospective case-control study, we evaluated whether a history of traumatic brain injury (TBI) associates with a diagnosis of FTD or modulates the clinical phenotype or onset age in FTD patients. We compared the prevalence of prior TBI between individuals with FTD (N = 218) and age and sex-matched AD patients (N = 214) or healthy controls (HC; N = 100). Based on the patient records, an individual was categorized to the TBI+ group if they were reported to have suffered from TBI during lifetime. The possible associations of TBI with age of onset and disease duration were also evaluated in the whole FTD patient group or separately in the sporadic and genetic FTD groups. The prevalence of previous TBI was the highest in the FTD group (19.3%) when compared to the AD group (13.1%, p = 0.050) or HC group (12%, p = 0.108, not significant). Preceding TBI was more often associated with the sporadic FTD cases than the C9orf72 repeat expansion-carrying FTD cases (p = 0.003). Furthermore, comparison of the TBI+ and TBI- FTD groups indicated that previous TBI was associated with an earlier onset age in the FTD patients (B = 3.066, p = 0.010). A preceding TBI associates especially with sporadic FTD and with earlier onset of symptoms. The results of this study suggest that TBI may be a triggering factor for the neurodegenerative processes in FTD. However, understanding the precise underlying mechanisms still needs further studies.

Medical and Psychiatric Risk Factors for Dementia in Veterans with and without Traumatic Brain Injury (TBI): A Nationwide Cohort Study

AbstractBackgroundTraumatic brain injury (TBI) is an important risk factor for dementia and is especially common among Veterans. It is unknown whether TBI exposure moderates the effect of other common medical/psychiatric comorbidities that are also important risk factors for dementia in Veterans. If treatable or preventable comorbidities are either especially common or risky in TBI‐exposed Veterans, then this may have important public health implications for dementia prevention.MethodWe conducted a retrospective cohort study using the Nationwide Veterans Health Administrative inpatient and outpatient data (2001‐2019). We identified all Veterans age 55 years with prior TBI and without baseline dementia (N = 95,139) and age/sex/race‐matched 1:2 with Veterans without prior TBI or baseline dementia (N = 190,278). We compared prevalence of seven common medical/psychiatric comorbidities (hypertension, coronary artery disease (CAD), diabetes, cerebrovascular disease (CVD), epilepsy, depression, and post‐traumatic stress disorder (PTSD)) and associated risk of incident dementia among Veterans with versus without prior TBI. We tested for interaction of each comorbidity with TBI on risk of dementia. We calculated risk of dementia associated with each comorbidity using multivariable hazard ratios (adjusting for demographics and all other comorbidities) and Fine‐Grey competing risk of death. We estimated population attributable risk (PAR) of dementia due to each comorbidity.ResultAll comorbidities were more prevalent among Veterans with TBI compared to those without TBI: hypertension +12.5%, CAD +13.6%, diabetes +7.9%, CVD +10.8%, epilepsy +5.7%, depression +21.5%, PTSD +14.9%). All comorbidities were associated with elevated risk for dementia among Veterans with and without TBI. However, there was a significant interaction with TBI such that point estimates were slightly lower among Veterans with TBI (adjusted HRs 1.02‐1.31) versus Veterans without TBI (adjusted HRs 1.03‐1.82). However, the overall PARs for dementia were higher in Veterans with versus without TBI for several comorbidities (depression 8.7% vs. 7.4%; hypertension 3.8% vs. 1.6%; CVD 3.7% vs. 2.0%; epilepsy 2.1% vs. 1.1%), due to their higher prevalence in Veterans with TBI.ConclusionWhile treating or preventing medical/psychiatric comorbidities among all Veterans remains a high public health priority, targeting depression, hypertension, CVD, and epilepsy may be especially important for dementia risk reduction among Veterans with prior TBI.

Ride the Wave: Continuous Electroencephalography is Indicated in the Management of Traumatic Brain Injury.

Introduction: Patients with traumatic brain injury (TBI) are at risk for seizures and other abnormalities that can have permanent adverse effects on the brain. We aimed to report the incidence of seizures and continuous EEG (cEEG) abnormalities after TBI and identify any risk factors associated with the development of these abnormalities. Materials and Methods: This retrospective study identified 245 adult patients with mild to severe TBI who had a cEEG performed within one week of admission to a Midwest Level 1 Trauma Center between July 2014 and July 2019. Trauma registry and electronic medical record (EPIC) data were extracted. Results: Twelve percent of patients with TBI developed seizures and an additional 23% demonstrated electrographic patterns that are correlated with risk for seizures (such as lateralized periodic patterns and sporadic epileptiform discharges). Fifty three percent of seizures would have been missed unless a cEEG was performed. Age, history of epilepsy or prior TBI, hypertension, bleeding disorder, and dementia were associated with an increased risk of developing seizures or higher risk patterns. Conclusions: Thirty-five percent of patients who presented with TBI were noted to have seizures or electrographic patterns associated with a higher risk of seizures. The incidence of cEEG abnormalities in this study is higher than previously reported and these patients are at risk for permanent neurological injury. We recommend the routine use of cEEG for all critically ill patients with TBI as over half of the seizures would have been missed if cEEG was not employed.

Continuous TBI Monitoring From Spontaneous Speech Using Parametrized Sinc Filters and a Cascading GRU.

Traumatic Brain Injury (TBI) is caused by a head injury that affects the brain, impairing cognitive and communication function and resulting in speech and language disorders. Over 80,000 individuals in the US suffer from long-term TBI disabilities and continuous monitoring after TBI is essential to facilitate rehabilitation and prevent regression. Prior work has demonstrated the feasibility of TBI monitoring from speech by leveraging advancements in Artificial Intelligence (AI) and speech processing technology. However, much of prior work explored TBI detection using scripted speech tasks such as diadochokinesis tests or reading a passage. Such scripted approaches require active user involvement that significantly burdens participants. Moreover, they are episodic, are not realistic, and do not provide a longitudinal picture of the user's TBI condition. This study proposes a continuous TBI monitoring from changes in acoustic features of spontaneous speech collected passively using the smartphone. Low-level acoustic features are extracted using parametrized Sinc filters (pSinc) that are then classified TBI (yes/no) using a cascading Gated Recurrent Unit (cGRU). The cGRU model utilizes a cell gate unit in the GRU to store and incorporate each individual's prediction history as prior knowledge into the model. In rigorous evaluation, our proposed method outperformed prior TBI classification methods on conversational speech recorded during patient-therapist discourses following TBI, achieving 83.87% balanced accuracy. Furthermore, unique words that are important in TBI prediction were identified using SHapley Additive exPlanations (SHAP). A correlation was also found between features acquired by the proposed method and coordination deficits following TBI.

Seizure Susceptibility and Sleep Disturbance as Biomarkers of Epileptogenesis after Experimental TBI.

Objectives: We investigated whether seizure susceptibility increases over weeks–months after experimental traumatic brain injury (TBI), and whether seizure susceptibility in rats predicts the development of post-traumatic epilepsy (PTE) or epileptiform activity. We further investigated whether rats develop chronic sleep disturbance after TBI, and whether sleep disturbance parameters—alone or in combination with pentylenetetrazol (PTZ) test parameters—could serve as novel biomarkers for the development of post-traumatic epileptogenesis. Methods: TBI was induced in adult male Sprague-Dawley rats with lateral fluid-percussion injury. Sham-operated experimental controls underwent craniectomy without exposure to an impact force. Seizure susceptibility was tested with a PTZ test (30 mg/kg, intraperitoneally) on day (D) 30, D60, D90, and D180 after TBI (n = 28) or sham operation (n = 16) under video electroencephalogram (vEEG). In the 7th post-injury month, rats underwent continuous vEEG monitoring to detect spontaneous seizures and assess sleep disturbances. At the end of the experiments, rats were perfused for brain histology. Results: In the TBI group, the percentage of rats with PTZ-induced seizures increased over time (adjusted p < 0.05 compared with D30). Combinations of three PTZ test parameters (latency to the first epileptiform discharge (ED), number of EDs, and number of PTZ-induced seizures) survived the leave-one-out validation for differentiating rats with or without epileptiform activity, indicating an area under the receiver operating curve (AUC) of 0.743 (95% CI 0.472–0.992, p = 0.05) with a misclassification rate of 36% on D90, and an AUC of 0.752 (95% CI 0.483–0.929, p < 0.05) with a misclassification rate of 32% on D180. Sleep analysis revealed that the number of transitions to N3 or rapid eye movement (REM) sleep, along with the total number of transitions, was increased in the TBI group during the lights-on period (all p < 0.05). The sleep fragmentation index during the lights-on period was greater in the TBI rats than in sham-operated rats (p < 0.05). A combination of sleep parameters showed promise as diagnostic biomarkers of prior TBI, with an AUC of 0.792 (95% CI 0.549–0.934, p < 0.01) and a misclassification rate of 28%. Rats with epilepsy or any epileptiform activity had more transitions from N3 to the awake stage (p < 0.05), and the number of N3–awake transitions differentiated rats with or without epileptiform activity, with an AUC of 0.857 (95% CI 0.651–1.063, p < 0.01). Combining sleep parameters with PTZ parameters did not improve the biomarker performance. Significance: This is the first attempt to monitor the evolution of seizure susceptibility over months in a well-described rat model of PTE. Our data suggest that assessment of seizure susceptibility and sleep disturbance can provide diagnostic biomarkers of prior TBI and prognostic biomarkers of post-traumatic epileptogenesis.

Hippocampal position and orientation as prognostic biomarkers for posttraumatic epileptogenesis: An experimental study in a rat lateral fluid percussion model.

ObjectiveThis study was undertaken to identify prognostic biomarkers for posttraumatic epileptogenesis derived from parameters related to the hippocampal position and orientation.MethodsData were derived from two preclinical magnetic resonance imaging (MRI) follow‐up studies: EPITARGET (156 rats) and Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx; University of Eastern Finland cohort, 43 rats). Epileptogenesis was induced with lateral fluid percussion‐induced traumatic brain injury (TBI) in adult male Sprague Dawley rats. In the EPITARGET cohort, T2∗‐weighted MRI was performed at 2, 7, and 21 days and in the EpiBioS4Rx cohort at 2, 9, and 30 days and 5 months post‐TBI. Both hippocampi were segmented using convolutional neural networks. The extracted segmentation mask was used for a geometric construction, extracting 39 parameters that described the position and orientation of the left and right hippocampus. In each cohort, we assessed the parameters as prognostic biomarkers for posttraumatic epilepsy (PTE) both individually, using repeated measures analysis of variance, and in combination, using random forest classifiers.ResultsThe extracted parameters were highly effective in discriminating between sham‐operated and TBI rats in both the EPITARGET and EpiBioS4Rx cohorts at all timepoints (t; balanced accuracy > .9). The most discriminating parameter was the inclination of the hippocampus ipsilateral to the lesion at t = 2 days and the volumes at t ≥ 7 days after TBI. Furthermore, in the EpiBioS4Rx cohort, we could effectively discriminate epileptogenic from nonepileptogenic animals with a longer MRI follow‐up, at t = 150 days (area under the curve = .78, balanced accuracy = .80, p = .0050), based on the orientation of both hippocampi. We found that the ipsilateral hippocampus rotated outward on the horizontal plane, whereas the contralateral hippocampus rotated away from the vertical direction.SignificanceWe demonstrate that assessment of TBI‐induced hippocampal deformation by clinically translatable MRI methodologies detects subjects with prior TBI as well as those at high risk of PTE, paving the way toward subject stratification for antiepileptogenesis studies.

Persistence of headache and its relation to other major sequelae following traumatic brain injury at 2-8years after deployment-related traumatic brain injury in veterans of Afghanistan and Iraq wars.

This study deals with headache in relation to other major sequelae of traumatic brain injury (TBI) in veterans of Iraq and Afghanistan wars over 8years after experiencing a deployment-related TBI (DTBI). TBI occurred in 14%-23% of veterans deployed to the Iraq or Afghanistan campaigns. This study evaluates sequelae of TBI (STBI) over 1-8years after a DTBI. This is a secondary, cross-sectional analysis of previously collected data, which was taken from review of medical records of the first 500 veterans with a DTBI seen in the TBI clinic of the Oklahoma City Veterans Health Center. This report deals with five of the most common STBIs and represents the presence and severity of, or absence of, the particular symptom at the time of a patient's initial visit to the clinic. All subjects were evaluated between June 1, 2008, and April 30, 2011. The STBI used here include: headache, dizziness, balance, coordination difficulties, and difficulty with decisions. In the TBI clinic, the burden of these symptoms was evaluated with a Likert Scale of none, mild, moderate, severe, or very severe. For this report, the scale was compressed into three categories: none, mild/moderate, and severe/very severe. Data were complete for age at TBI and mechanism of TBI in 500 subjects, for symptom severity in 497 subjects, for TBI severity in 491 subjects, and for presence of prior TBI in 496 subjects. For the 497 subjects with complete symptom severity data, headache was seen in 476 (95.8%) and absent in 21 (4.2%). Regarding headache severity, 236 (47.5%) reported mild/moderate and 240 (48.3%) reported severe/very severe headache burden. For other sequelae, including severity of dizziness, balance, and coordination problems, these symptoms were absent in 85 (17.1%), 85 (17.1%), and 106 (21.3%) patients, respectively; of mild/moderate severity in 356 (71.6%), 355 (71.4%), and 321 (64.6%) patients; and of severe/very severe intensity in 56 (11.3%), 57 (11.5%), and 70 (14.1%) patients. Difficulty with decisions, which was used as an indication of cognitive difficulty, was noted in 429 (86.3%) of the subjects, of which 252 (50.7%) noted mild/moderate and 177 (35.6%) severe/very severe intensity. To evaluate changes over time, the subjects were divided into 2-year cohorts of 1-2, 3-4, 5-6, and 7-8years since DTBI. Comparing symptom burden within these four 2-year cohorts, there was no statistically significant change in symptom burden analyzing by time interval from DTBI to TBI clinic evaluation. For analysis by severity of the DTBI in 491 subjects with complete data, categories were constructed based on alteration of consciousness (AOC) or duration of loss of consciousness (LOC) as follows: AOC (264/491 [53.8%]); LOC <1min (95/491 [19.4%]); LOC, 1-30min (115/491 [23.4%]); and LOC >30min (17/491 [3.5%]). The proportion of subjects with severe/very severe symptom intensity increased as the severity of the DTBI increased (from p=0.043 to p=0.001). Additional evaluations included groupings by age at DTBI (20-29, 30-39, and ≥40years), by presence or absence of a TBI prior to the DTBI, and by causation of the DTBI (blast or direct head trauma). No significant differences were observed with any of these comparisons. For veterans experiencing a DTBI, these TBI-related sequelae persist with little improvement over time up to 8years. A trend toward symptoms becoming worse as DTBI severity increased was observed. Headache was the most frequent sequela of TBI, occurring in 96% of the patients with almost half of these reporting severe/very severe intensity of headache burden. The basis for the prolonged persistence of these STBI is not known.

Individuals with Chronic Mild-to-Moderate Traumatic Brain Injury Exhibit Decreased Neuromuscular Complexity During Gait

Background Synergy analysis provides a means of quantifying the complexity of neuromuscular control during gait. Prior studies have shown evidence of reduced neuromuscular complexity during gait in individuals with neurological disorders associated with stroke, cerebral palsy, and Parkinson’s disease. Objective The purpose of this study was to investigate neuromuscular complexity during gait in individuals who experienced a prior traumatic brain injury (TBI) that resulted in chronic balance deficits. Methods We measured and analyzed lower extremity electromyographic data during treadmill and overground walking for 44 individuals with residual balance deficits from a mild-to-moderate TBI at least 1 year prior. We also tested 20 unimpaired controls as a comparison. Muscle synergies were calculated for each limb using non-negative matrix factorization of the activation patterns for 6 leg muscles. We quantified neuromuscular complexity using Walk-DMC, a normalized metric of the total variance accounted for by a single synergy, in which a Walk-DMC score of 100 represents normal variance accounted for. We compared group average synergy structures and inter-limb similarity using cosine similarity. We also quantified each individual’s gait and balance using the Sensory Organization Test, the Dynamic Gait Index, and the Six-Minute Walk Test. Results Neuromuscular complexity was diminished for individuals with a prior TBI. Walk-DMC averaged 92.8 ± 12.3 for the TBI group during overground walking, which was significantly less than seen in controls (100.0 ± 10.0). Individuals with a prior TBI exhibited 13% slower overground walking speeds than controls and reduced performance on the Dynamic Gait Index (18.5 ± 4.7 out of 24). However, Walk-DMC measures were insufficient to stratify variations in assessments of gait and balance performance. Group average synergy structures were similar between groups, although there were considerable between-group differences in the inter-limb similarity of the synergy activation vectors. Conclusions Individuals with gait and balance deficits due to a prior TBI exhibit evidence of decreased neuromuscular complexity during gait. Our results suggest that individuals with TBI exhibit similar muscle synergy weightings as controls, but altered control of the temporal activation of these muscle weightings.

Effect of traumatic brain injury on mild behavioral impairment domains prior to all-cause dementia diagnosis and throughout disease progression.

Traumatic brain injury (TBI) may alter dementia progression, although co-occurring neuropsychiatric symptoms (NPS) have received less attention. Originally designed to evaluate behavioral disruption prior to dementia diagnosis, the mild behavioral impairment (MBI) construct relates NPS to underlying neural circuit disruptions, with probable relevance across the progression of neurodegenerative disease. Therefore, the MBI construct may represent a valuable tool to identify and evaluate related NPS both preceding diagnosis of all-cause dementia throughout the progression of disease, representing an important area of inquiry regarding TBI and dementia. This investigation sought to evaluate the effect of TBI on NPS related by the MBI construct in participants progressing from normal cognitive status to all-cause dementia. Using National Alzheimer's Coordinating Center data, individuals progressing from normal cognition to all-cause dementia (clinician diagnosed) over 7.6 ± 3.0 years were studied to estimate prevalence of MBI domains in 124 participants with prior TBI history (57 with loss of consciousness [LOC] <5 minutes, 22 with LOC >5 min, 45 unknown severity) compared to 822 without. MBI domain prevalence was evaluated (1) prior to dementia onset (including only time points preceding time at dementia diagnosis, as per MBI's original definition) and (2) throughout dementia progression (evaluating all available time points, including both before and after dementia diagnosis). More severe TBI (LOC >5 minutes) was associated with the social inappropriateness MBI domain (adjusted odds ratio = 4.034; P = 0.024) prior to dementia onset, and the abnormal perception/thought content domain looking across dementia progression (adjusted hazard ratio [HRadj] = 3.703; P = 0.005). TBI (all severities) was associated with the decreased motivation domain looking throughout dementia progression (HRadj. = 1.546; P = 0.014). TBI history is associated with particular MBI profiles prior to onset and throughout progression of dementia. Understanding TBI's impact on inter-related NPS may help elucidate underlying neuropathology with implications for surveillance, detection, and treatment of behavioral concerns in aging TBI survivors. The mild behavioral impairment (MBI) construct links related neuropsychiatric symptoms (NPS) by probable underlying neural network dysfunction.Traumatic brain injury (TBI) with loss of consciousness (LOC) > 5 minutes was associated with pre-dementia social inappropriateness.TBI was associated with decreased motivation looking across dementia progression.TBI with LOC > 5 minutes was associated with abnormal perception/thought content.The MBI construct may be useful for examining related NPS across dementia progression.

Association of Military Employment With Late-Life Cognitive Decline and Dementia: A Population-Based Prospective Cohort Study.

As the number of U.S. veterans over age 65 has increased, interest in whether military service affects late-life health outcomes has grown. Whether military employment is associated with increased risk of cognitive decline and dementia remains unclear. We used data from 4,370 participants of the longitudinal Adult Changes in Thought (ACT) cohort study, enrolled at age 65 or older, to examine whether military employment was associated with greater cognitive decline or higher risk of incident dementia in late life. We classified persons as having military employment if their first or second-longest occupation was with the military. Cognitive status was assessed at each biennial Adult Changes in Thought study visit using the Cognitive Abilities Screening Instrument, scored using item response theory (CASI-IRT). Participants meeting screening criteria were referred for dementia ascertainment involving clinical examination and additional cognitive testing. Primary analyses were adjusted for sociodemographic characteristics and APOE genotype. Secondary analyses additionally adjusted for indicators of early-life socioeconomic status and considered effect modification by age, gender, and prior traumatic brain injury with loss of consciousness TBI with LOC. Overall, 6% of participants had military employment; of these, 76% were males. Military employment was not significantly associated with cognitive change (difference in modeled 10-year cognitive change in CASI-IRT scores in SD units (95% confidence interval [CI]): -0.042 (-0.19, 0.11), risk of dementia (hazard ratio [HR] [95% CI]: 0.92 [0.71, 1.18]), or risk of Alzheimer's disease dementia (HR [95% CI]: 0.93 [0.70, 1.23]). These results were robust to additional adjustment and sensitivity analyses. There was no evidence of effect modification by age, gender, or traumatic brain injury with loss of consciousness. Among members of the Adult Changes in Thought cohort, military employment was not associated with increased risk of cognitive decline or dementia. Nevertheless, military veterans face the same high risks for cognitive decline and dementia as other aging adults.

A-127 The Interplay of Social Perception and Psychiatric Symptoms in a Case of Traumatic Brain Injury

Abstract Objective Acquired impairment in social perception (SP) is relatively common following moderate to severe traumatic brain injury (TBI), with up to 39% of these individuals experiencing deficient facial affect recognition. Formal assessment of SP is not common practice, despite evidence of this as a predictor of social functioning. We present the case of a 35-year-old, Caucasian male with new onset paranoid/delusional (P/D) thought processes in the context of prior TBI. Method The patient’s TBI (unknown severity) occurred 17 years prior and resulted in prolonged (&amp;gt;1 year) hospitalization, followed by intensive rehabilitation services. He reported residual, stable difficulties with attention, processing speed, executive functioning, and memory. Post-TBI, he was living independently with few external supports. Following a traumatic encounter with a family member (nine months prior), the patient developed P/D thought processes and a marked decline in functioning, resulting in three psychiatric hospitalizations. Brain MRI (Figure 1) revealed encephalomalacia and gliosis in the bilateral inferior frontal lobes anteriorly, high frontoparietal lobes, and bilateral (L &amp;gt; R) temporal lobes. Neuropsychology was consulted to clarify diagnosis/etiology and assess functional status. Results (Table 1). Evaluation results revealed non-amnestic memory impairment and variable language and processing speed. Performances on measures of SP revealed a notable weakness in the context of current intellectual performances. Conclusions This case highlights the importance of formally assessing SP in cases of TBI. Underlying SP difficulties in the context of a traumatic event may have increased vulnerability to psychiatric decompensation. Evaluation of SP allowed for enhanced understanding of the interplay between cognitive and psychiatric symptoms.

White matter and neurite morphology differ in psychogenic nonepileptic seizures.

ObjectiveTo further evaluate the relationship between the clinical profiles and limbic and motor brain regions and their connecting pathways in psychogenic nonepileptic seizures (PNES). Neurite Orientation Dispersion and Density Indices (NODDI) multicompartment modeling was used to test the relationships between tissue alterations in patients with traumatic brain injury (TBI) and multiple psychiatric symptoms.MethodsThe sample included participants with prior TBI (TBI; N = 37) but no PNES, and with TBI and PNES (TBI + PNES; N = 34). Participants completed 3T Siemens Prisma MRI high angular resolution imaging diffusion protocol. Statistical maps, including fractional anisotropy (FA), mean diffusivity (MD), neurite dispersion [orientation dispersion index (ODI)] and density [intracellular volume fraction (ICVF), and free water (i.e., isotropic) volume fraction (V‐ISO)] signal intensity, were generated for each participant. Linear mixed‐effects models identified clusters of between‐group differences in indices of white matter changes. Pearson’s r correlation tests assessed any relationship between signal intensity and psychiatric symptoms.ResultsCompared to TBI, TBI + PNES revealed decreases in FA, ICVF, and V‐ISO and increases in MD for clusters within cingulum bundle, uncinate fasciculus, fornix/stria terminalis, and corticospinal tract pathways (cluster threshold α = 0.05). Indices of white matter changes for these clusters correlated with depressive, anxiety, PTSD, psychoticism, and somatization symptom severity (FDR threshold α = 0.05). A follow‐up within‐group analysis revealed that these correlations failed to reach the criteria for significance in the TBI + PNES group alone.InterpretationThe results expand support for the hypothesis that alterations in pathways comprising the specific PNES network correspond to patient profiles. These findings implicate myelin‐specific changes as possible contributors to PNES, thus introducing novel potential treatment targets.

Substance use on admission toxicology screen is associated with peri-injury factors and six-month outcome after traumatic brain injury: A TRACK-TBI Pilot study

Substance use is commonly associated with traumatic brain injury (TBI). We investigate associations between active substance use, peri-injury factors, and outcome after TBI across three U.S. Level I trauma centers. TBI subjects from the prospective Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot (TRACK-TBI Pilot) with Marshall computed tomography (CT) score 1–3, no neurosurgical procedure/operation, and admission urine toxicology screen (tox+/−) were extracted. Associations between tox+/−, comorbidities, hospital variables, and six-month functional (GOSE) and neuropsychiatric (PCL-C, BSI18, RPQ-13, SWLS) outcomes were analyzed. Multivariable regression was performed for associations significant on univariate analysis with odds ratios (mOR) presented. Significance assessed at p < 0.05. In 133 subjects, tox+/tox− were 29.1%/72.9%. Tox+ was younger (35.5/43.6-years, p = 0.018), trended toward male sex (80.6%/63.9%, p = 0.067), was associated with history of seizures (27.8%/10.3%, p = 0.012), self-reported substance use (44.4%/17.5%, p = 0.001), prior TBI (58.8%/34.1%, p = 0.009), GCS < 15 (69.4%/48.4%, p = 0.031) and blood alcohol level >0.08-mg/dl (55.6%/30.8%, p = 0.022). In CT-negative subjects, tox+ was associated with increased hospital admission (95.7%/66.7%, p = 0.034). At six-months, tox+ was associated with screening positive for post-traumatic stress disorder (PCL-C: 40.0%/15.9%; mOR = 8.24, p = 0.022) and psychiatric symptoms (BSI18: 40.0%/14.3%, mOR = 11.06, p = 0.023). Active substance use in TBI may confound GCS assessment, triage to higher level of care, and be associated with increased six-month neuropsychiatric symptoms. Substance use screening should be integrated into standard emergency/acute care TBI protocols to optimize management and resource utilization. Clinicians should be vigilant in providing education, counselling, and follow-up for TBI patients with substance use.

Physical and Functional Impairment Among Older Adults With a History of Traumatic Brain Injury.

To examine the association of lifetime history of traumatic brain injury (TBI) with later-life physical impairment (PI) and functional impairment (FI) and to evaluate the impact of neurobehavioral symptoms that frequently co-occur with TBI on these relations. A total of 1148 respondents to the 2014 Wave of the Health and Retirement Study, a nationally representative survey of older community-dwelling adults, randomly selected to participate in a TBI exposure survey. They reported no prior TBI (n = 737) or prior TBI (n = 411). Cross-sectional survey study. Physical impairment (self-reported difficulty with ≥1 of 8 physical activities); FI (self-reported difficulty with ≥1 of 11 activities of daily living); self-reported current neurobehavioral symptoms (pain, sleep problems, depression, subjective memory impairment); The Ohio State University TBI Identification Method (OSU-TBI-ID)-short form. Stepwise logistic regression models ([1] unadjusted; [2] adjusted for demographics and medical comorbidities; [3] additionally adjusted for neurobehavioral symptoms) compared PI and FI between TBI groups. Traumatic brain injury-exposed (mean: 33.6 years postinjury) respondents were younger, less likely to be female, and reported more comorbidities and neurobehavioral symptoms. Although TBI was significantly associated with increased odds of PI and FI in unadjusted models and models adjusted for demographics/comorbidities (adjusted odds ratio, 95% confidence interval: PI 1.62, 1.21-2.17; FI 1.60, 1.20-2.14), this association was no longer statistically significant after further adjustment for neurobehavioral symptoms. History of TBI is associated with substantial PI and FI among community-dwelling older adults. Further research is warranted to determine whether aggressive management of neurobehavioral symptoms in this population may mitigate long-term PI and FI in this population.

Type 2 Diabetes Predicts Increased Risk of Neurodegenerative Complications in Veterans Suffering Traumatic Brain Injury.

Obese type 2 diabetes and traumatic brain injury are associated with persistent peripheral and neuro-inflammation, respectively. We tested whether adult type 2 diabetes increased the hazard rate for neurodegeneration complications following traumatic brain injury. Retrospective chart review of patients treated at the Veterans Affairs New Jersey Healthcare System between 2016-2019 and having a diagnosis of prior traumatic brain injury was performed in adult veterans, age 50 years or older. Cox proportional hazards regression analysis was used to identify risk factors predictive of an increased risk of neurodegeneration, i.e. worsening major depression, dementia or Parkinson's disease following traumatic brain injury. Type 2 diabetes predicted a nearly three-fold increased hazard ratio (HR = 2.95, 95% CI 1.15-7.56, P =0.02) for the occurrence of worsening major depression, dementia or Parkinson's disease in eighty adults age 50 years or older who had experienced prior traumatic brain injury. After adjusting for other covariates, hypertension (HR= 4.15, 95% CI 1.21-14.29, P =0.02) was significant and body mass index (HR=1.14, 95% CI 0.99-1.30; P=0.06) modestly significant predictors of the risk for the time to first occurrence of the composite neurodegenerative outcome. Type 2 diabetes, hypertension and higher body mass index increase the hazard for the occurrence of worsening depression, Parkinson's disease and dementia following traumatic brain injury in middle-aged and older adults.

Prior head injury but not sex or sports-participation affects expectations for post-injury rest and activity in simulated mild traumatic brain injury

Rest acutely followed by a gradual return to activity is commonly recommended for mild traumatic brain injury (TBI). However, the general public’s rest and activity expectations for this injury are unknown, as are the individual factors that might affect them. 165 individuals completed an online survey. A series of between-groups comparisons of expectations for the week following a mild TBI was performed. The comparisons were between individuals with or without a prior mild TBI; sports-playing versus non-sports-playing individuals, and; females versus males. Expectations were elicited for 39 everyday behaviours referred to in mild TBI patient advice. Compared to a rating indicating ‘no change’ in the amount of pre-injury activity, “rest” was expected for 37 items (p’s < .05). Expectations were not different based on participants’ sex or sports-participation. However, for seven predominantly cognitive items such as studying, a prior injury increased rest expectations (p < .05; small-to-medium effects). The findings indicate that whilst the proposed activity restrictions are appropriate for some circumstances such as acutely postinjury, they have the potential to be overly strong. To address this potential, especially with first-ever injury, clinicians and sports officials should check their patient’s postinjury rest and activity plans when providing active rest advice.

Traumatic brain injury and hazardous/harmful drinking: Concurrent and single associations with poor mental health and roadway aggression

This study describes the association among lifetime traumatic brain injury (TBI) and past year hazardous/harmful drinking, as well as their unique and synergistic effects, on mental health problems and roadway aggression among Canadian adults. A cross-sectional sample of 6074 Ontario adults aged 18 years or older were surveyed between 2011 and 2013. TBI was defined as trauma to the head resulting in loss of consciousness or overnight hospitalization. Past year hazardous/harmful drinking was assessed using the Alcohol Use Disorders Identification Test. An estimated 13.1% (95%CI:12.0,14.2) adults reported a prior TBI (no hazardous/harmful drinking), 2.7% (95%CI:2.2,3.3) reported a prior TBI while concurrently screening positive for past year hazardous/harmful drinking and 9.8% (95%CI:8.9,10.9) screened positive for hazardous/harmful drinking (no TBI). Men had significantly higher odds of exhibiting all three conditions compared to women, especially for the concurrent class. Younger adults had significantly greater odds of hazardous/harmful drinking, or the concurrent class compared to adults 55 years and older. Adults in any of the three conditions had greater odds for mental health problems and roadway aggression. Concordance of both conditions corresponded to a greater than additive effect and greater odds of mild roadway aggression, than either condition alone. Results show that singly and jointly, these conditions are associated with adverse health and behavioral impediments.

Is traumatic brain injury a risk factor for neurodegeneration? A meta-analysis of population-based studies

BackgroundTo determine the association of prior traumatic brain injury (TBI) with subsequent diagnosis of neurodegeneration disease.MethodsAll studies from 1980 to 2016 reporting TBI as a risk factor for diagnoses of interest were identified by searching PubMed, Embase, study references, and review articles. The data and study design were assessed by 2 investigators independently. A meta-analysis was performed by RevMan 5.3.ResultsThere were 18 studies comprising 3,263,207 patients. Meta-analysis revealed a significant association of prior TBI with subsequent dementia. The pooled odds ratio (OR) for TBI on development of dementia, FTD and TDP-43 associated disease were 1.93 (95% CI 1.47–2.55, p < 0.001), 4.44 (95% CI 3.86–5.10, p < 0.001), and 2.97 (95% CI 1.35–6.53, p < 0.001). However, analyses of individual diagnoses found no evidence that the risk of Alzheimer’s disease, and Parkinson’s disease in individuals with previous TBI compared to those without TBI.ConclusionsHistory of TBI is not associated with the development of subsequent neurodegeneration disease. Care must be taken in extrapolating from these results because no suitable criteria define post TBI neurodegenerative processes. Therefore, further research in this area is needed to confirm these questions and uncover the link between TBI and neurodegeneration disease.