Prior traumatic brain injury is a risk factor for in-hospital mortality in moderate to severe traumatic brain injury: a TRACK-TBI cohort study.

Objectives: An estimated 14-23% of patients with traumatic brain injury (TBI) incur multiple lifetime TBIs. The relationship between prior TBI and outcomes in patients with moderate to severe TBI (msTBI) is not well delineated. We examined the associations between prior TBI, in-hospital mortality, and outcomes up to 12 months after injury in a prospective US msTBI cohort. Methods: Data from hospitalized subjects with Glasgow Coma Scale score of 3-12 were extracted from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury Study (enrollment period: 2014-2019). Prior TBI with amnesia or alteration of consciousness was assessed using the Ohio State University TBI Identification Method. Competing risk regressions adjusting for age, sex, psychiatric history, cranial injury and extracranial injury severity examined the associations between prior TBI and in-hospital mortality, with hospital discharged alive as the competing risk. Adjusted HRs (aHR (95% CI)) were reported. Multivariable logistic regressions assessed the associations between prior TBI, mortality, and unfavorable outcome (Glasgow Outcome Scale-Extended score 1-3 (vs. 4-8)) at 3, 6, and 12 months after injury. Results: Of 405 acute msTBI subjects, 21.5% had prior TBI, which was associated with male sex (87.4% vs. 77.0%, p=0.037) and psychiatric history (34.5% vs. 20.7%, p=0.010). In-hospital mortality was 10.1% (prior TBI: 17.2%, no prior TBI: 8.2%, p=0.025). Competing risk regressions indicated that prior TBI was associated with likelihood of in-hospital mortality (aHR=2.06 (1.01-4.22)), but not with hospital discharged alive. Prior TBI was not associated with mortality or unfavorable outcomes at 3, 6, and 12 months. Conclusions: After acute msTBI, prior TBI history is independently associated with in-hospital mortality but not with mortality or unfavorable outcomes within 12 months after injury. This selective association underscores the importance of collecting standardized prior TBI history data early after acute hospitalization to inform risk stratification. Prospective validation studies are needed. Level of evidence: IV. Trial registration number: NCT02119182.

Psychiatric Disorders Are Common Among Older US Veterans Prior to Traumatic Brain Injury.

OBJECTIVE: To estimate the impact of traumatic brain injury (TBI) on prevalence of posttraumatic stress disorder (PTSD), depression, and alcohol and substance use disorders. SETTING: A random sample of Veteran's Health Administration data. PARTICIPANTS: A total of 14 116 veterans aged ≥55 with incident late-life TBI between October 1, 1999, and September 31, 2021, were matched 1:3 on age and TBI date to 42 678 veterans without TBI. DESIGN: Retrospective cohort study. MAIN MEASURES: PTSD, depression, and alcohol and substance use disorders were identified using diagnostic codes. Participants were censored after the first diagnosis during the year before and the year after the TBI or matched date. Prevalence rates of PTSD, depression, alcohol, and substance use disorders were compared before and after incident TBI or matched date using Poisson regression. RESULTS: Pre-TBI prevalence rates of disorders were higher among those with TBI relative to those without TBI. Pre-TBI PTSD prevalence rates (per 1000 person-years) were 126.3 (95% CI, 120.2-132.4) compared to 21.5 (95% CI, 20.1-22.9) in the non-TBI cohort. In adjusted models, TBI was not associated with an increase in the prevalence of any of the studied disorders. CONCLUSIONS: Prevalence rates of depression, PTSD, and alcohol and substance use disorders were 5 to 10 times higher among older veterans before incident TBI. We did not observe an increase in the prevalence of these disorders after incident TBI. Older veterans with these disorders may be at increased risk for TBI.

Cognitive function in adolescence and the risk of early-onset stroke.

BACKGROUND: Stroke is increasingly prevalent at younger ages but the risk factors are uncertain. We examined the association between adolescent cognitive function and early-onset stroke. METHODS: This was a nationwide population-based cohort study of 1 741 345 Israeli adolescents (42% women) who underwent comprehensive cognitive function tests at age 16-20 years, before mandatory military service, during 1987-2012. Cognitive function (range: 1-9) was categorised as low (1-3, corresponding to IQ score below 89), medium (4-7, IQ score range: 89-118), or high (8-9, IQ score above 118). Participant data were linked to the Israeli National Stroke Registry. Cox proportional hazard models were used to estimate risks for the first occurrence of ischaemic stroke during 2014-2018. RESULTS: During 8 689 329 person-years of follow-up, up to a maximum age of 50 years, 908 first stroke events occurred (767 ischaemic and 141 haemorrhagic). Compared with a reference group of people with high cognitive function, body mass index-adjusted and sociodemographic-adjusted HRs (95% CIs) for early-onset stroke were 1.78 (1.33-2.38) in medium and 2.68 (1.96-3.67) in low cognitive function groups. There was evidence of a dose-response relationship (P for trend <0.0001) such that one-unit of lower cognitive function z-score was associated with a 33% increased risk of stroke (1.33; 1.23-1.42). These associations were similar for ischaemic stroke but lower for haemorrhagic stroke; persisted in sensitivity analyses that accounted for diabetes status and hypertension; and were evident before age 40 years. CONCLUSIONS: Alongside adolescent obesity and hypertension, lower cognitive function may be a risk factor for early-onset stroke.

Incidence of Traumatic Brain Injury in a Longitudinal Cohort of Older Adults.

Importance: Traumatic brain injury (TBI) occurs at the highest rate in older adulthood and increases risk for cognitive impairment and dementia. Objectives: To update existing TBI surveillance data to capture nonhospital settings and to explore how social determinants of health (SDOH) are associated with TBI incidence among older adults. Design, Setting, and Participants: This nationally representative longitudinal cohort study assessed participants for 18 years, from August 2000 through December 2018, using data from the Health and Retirement Study (HRS) and linked Medicare claims dates. Analyses were completed August 9 through December 12, 2022. Participants were 65 years of age or older in the HRS with survey data linked to Medicare without a TBI prior to HRS enrollment. They were community dwelling at enrollment but were retained in HRS if they were later institutionalized. Exposures: Baseline demographic, cognitive, medical, and SDOH information from HRS. Main Outcomes and Measures: Incident TBI was defined using inpatient and outpatient International Classification of Diseases, Ninth or Tenth Revision, diagnosis codes received the same day or within 1 day as the emergency department (ED) visit code and the computed tomography (CT) or magnetic resonance imaging (MRI) code, after baseline HRS interview. A cohort with TBI codes but no ED visit or CT or MRI scan was derived to capture diagnoses in nonhospital settings. Descriptive statistics and bivariate associations of TBI with demographic and SDOH characteristics used sample weights. Fine-Gray regression models estimated associations between covariates and TBI, with death as a competing risk. Imputation considering outcome and complex survey design was performed by race and ethnicity, sex, education level, and Area Deprivation Index percentiles 1, 50, and 100. Other exposure variables were fixed at their weighted means. Results: Among 9239 eligible respondents, 5258 (57.7%) were female and 1210 (9.1%) were Black, 574 (4.7%) were Hispanic, and 7297 (84.4%) were White. Mean (SD) baseline age was 75.2 (8.0) years. During follow-up (18 years), 797 (8.9%) of respondents received an incident TBI diagnosis with an ED visit and a CT code within 1 day, 964 (10.2%) received an incident TBI diagnosis and an ED code, and 1148 (12.9%) received a TBI code with or without an ED visit and CT scan code. Compared with respondents without incident TBI, respondents with TBI were more likely to be female (absolute difference, 7.0 [95% CI, 3.3-10.8]; P < .001) and White (absolute difference, 5.1 [95% CI, 2.8-7.4]; P < .001), have normal cognition (vs cognitive impairment or dementia; absolute difference, 6.1 [95% CI, 2.8-9.3]; P = .001), higher education (absolute difference, 3.8 [95% CI, 0.9-6.7]; P < .001), and wealth (absolute difference, 6.5 [95% CI, 2.3-10.7]; P = .01), and be without baseline lung disease (absolute difference, 5.1 [95% CI, 3.0-7.2]; P < .001) or functional impairment (absolute difference, 3.3 [95% CI, 0.4-6.1]; P = .03). In adjusted multivariate models, lower education (subdistribution hazard ratio [SHR], 0.73 [95% CI, 0.57-0.94]; P = .01), Black race (SHR, 0.61 [95% CI, 0.46-0.80]; P < .001), area deprivation index national rank (SHR 1.00 [95% CI 0.99-1.00]; P = .009), and male sex (SHR, 0.73 [95% CI, 0.56-0.94]; P = .02) were associated with membership in the group without TBI. Sensitivity analyses using a broader definition of TBI yielded similar results. Conclusions and Relevance: In this longitudinal cohort study of older adults, almost 13% experienced incident TBI during the 18-year study period. For older adults who seek care for TBI, race and ethnicity, sex, and SDOH factors may be associated with incidence of TBI, seeking medical attention for TBI in older adulthood, or both.

Healthy Days at Home Among Older Medicare Beneficiaries With Traumatic Brain Injury Requiring Inpatient Rehabilitation.

OBJECTIVE: The objectives of this study were to characterize and identify correlates of healthy days at home (HDaH) before and after TBI requiring inpatient rehabilitation. SETTING: Inpatient hospital, nursing home, and home health services. PARTICIPANTS: Average of n = 631 community-dwelling fee-for-service age 66+ Medicare beneficiaries across 30 replicate samples who were hospitalized for traumatic brain injury (TBI) between 2012 and 2014 and admitted to an inpatient rehabilitation facility (IRF) within 72 hours of hospital discharge. DESIGN: Retrospective study using data from Medicare claims supplemented with data from the National Trauma Databank. MAIN MEASURES: The primary outcome, HDaH, was calculated as time alive not using inpatient hospital, nursing home, and home health services in the year before TBI hospitalization and after IRF discharge. RESULTS: We found HDaH declined from 93.2% in the year before TBI hospitalization to 65.3% in the year after IRF discharge (73.6% among survivors only). Most variability in HDaH was: (1) in the first 3 months after discharge and (2) by discharge disposition, with persons discharged from IRF to another acute hospital having the worst prognosis for utilization and death. In negative binomial regression models, the strongest predictors of HDaH in the year after discharge were rehabilitation Functional Independence Measure mobility score ( ß  = 0.03; 95% CI, 0.002-0.06) and inpatient Charlson Comorbidity Index score ( ß  = - 0.06; 95% CI, -0.13 to 0.001). Dual Medicaid eligible was associated with less HDaH among survivors ( ß  = - 0.37; 95% CI, -0.66 to -0.07). CONCLUSION: In this study, among community-dwelling older adults with TBI, we found a notable decrease in the proportion of time spent alive at home without higher-level care after IRF discharge compared to before TBI. The finding that physical disability and comorbidities were the biggest drivers of healthy days alive in this population suggests that a chronic disease management model is required for older adults with TBI to manage their complex health care needs.

Linking Type and Extent of Head Trauma to Cavum Septum Pellucidum in Older Adults With and Without Alzheimer Disease and Related Dementias.

BACKGROUND AND OBJECTIVES: Cavum septum pellucidum (CSP) is a common but nonspecific MRI finding in individuals with prior head trauma. The type and extent of head trauma related to CSP, CSP features specific to head trauma, and the impact of brain atrophy on CSP are unknown. We evaluated CSP cross-sectionally and longitudinally in healthy and clinically impaired older adults who underwent detailed lifetime head trauma characterization. METHODS: This is an observational cohort study of University of California, San Francisco Memory and Aging Center participants (healthy controls [HCs], those with Alzheimer disease or related dementias [ADRDs], subset with traumatic encephalopathy syndrome [TES]). We characterized traumatic brain injury (TBI) and repetitive head impacts (RHI) through contact/collision sports. Study groups were no RHI/TBI, prior TBI only, prior RHI only, and prior RHI + TBI. We additionally looked within TBI (1, 2, or 3+) and RHI (1-4, 5-10, and 11+ years). All underwent baseline MRI, and 67% completed a second MRI (median follow-up = 5.4 years). CSP measures included grade (0-4) and length (millimeters). Groups were compared on likelihood of CSP (logistic regression, odds ratios [ORs]) and whether CSP length discriminated groups (area under the curve [AUC]). RESULTS: Our sample included 266 participants (N = 160 HCs, N = 106 with ADRD or TES; age 66.8 ± 8.2 years, 45.3% female). Overall, 123 (49.8%) participants had no RHI/TBI, 52 (21.1%) had TBI only, 41 (16.6%) had RHI only, 31 (12.6%) had RHI + TBI, and 20 were classified as those with TES (7.5%). Compared with no RHI/TBI, RHI + TBI (OR 3.11 [1.23-7.88]) and TES (OR 11.6 [2.46-54.8]) had greater odds of CSP. Approximately 5-10 years (OR 2.96 [1.13-7.77]) and 11+ years of RHI (OR 3.14 [1.06-9.31]) had higher odds of CSP. CSP length modestly discriminated participants with 5-10 years (AUC 0.63 [0.51-0.75]) and 11+ years of prior RHI (AUC 0.69 [0.55-0.84]) from no RHI/TBI (cut point = 6 mm). Strongest effects were noted in analyses of American football participation. Longitudinally, CSP grade was unchanged in 165 (91.7%), and length was unchanged in 171 (95.5%) participants. DISCUSSION: Among older adults with and without neurodegenerative disease, risk of CSP is driven more by duration (years) of RHI, especially American football, than number of TBI. CSP length (≥6 mm) is relatively specific to individuals who have had substantial prior RHI. Neurodegenerative disease and progressive atrophy do not clearly influence development or worsening of CSP.

Prognostic Value of Frailty for Outcome Following Traumatic Brain Injury: A Systematic Review and Meta-Analysis.

Frailty is a known predictor of negative health outcomes. The role of frailty in predicting outcomes after traumatic brain injury (TBI), however, is unclear. This systematic review aimed to evaluate the association between frailty and adverse outcomes in patients with TBI. We identified relevant articles that investigated the relationship between frailty and outcomes in patients with TBI by searching PubMed/MEDLINE, Web of Science, Scopus, and EMBASE from inception until 23 March 2023. To evaluate the risk of bias in the included studies, we utilized the Newcastle-Ottawa Scale (NOS). In addition, quantitative synthesis and meta-analyses were performed. We identified 12 studies that met our inclusion criteria; three were prospective. Of included studies, eight had low risk, three had moderate risk, and one had high risk of bias. Frailty was significantly associated with death in five studies, with an increased risk of in-hospital death and complications observed in frail patients. Frailty was associated with longer hospital stays and unfavorable outcome measured by the Extended Glasgow Outcome Scale (GOSE) in four studies. The meta-analysis found that higher frailty significantly increased the odds of non-routine discharge and unfavorable outcome as measured by GOSE scores of 4 or lower. The pooled odds ratio (OR) for non-routine discharge, was 1.80, with a 95% confidence interval (CI) of 1.15-2.84; and for unfavorable outcome, it was 1.91, with a 95% CI of 1.09-3.36. The analysis, however, did not find a significant predictive role for frailty on death (30-day or in-hospital death). The OR for higher frailty and death was 1.42 with a 95% CI of 0.92-2.19. Frailty should be considered in the evaluation of patients with TBI to identify those who may be at increased risk of negative outcomes.

Alzheimer's pathology is associated with altered cognition, brain volume, and plasma biomarker patterns in traumatic encephalopathy syndrome.

BACKGROUND: Traumatic encephalopathy syndrome (TES) is a clinical phenotype sensitive but non-specific to underlying chronic traumatic encephalopathy (CTE) neuropathology. However, cognitive symptoms of TES overlap with Alzheimer's disease (AD), and features of AD pathology like beta-amyloid (Aß) plaques often co-occur with CTE, making clinical-to-pathological conclusions of TES diagnoses challenging. We investigated how Alzheimer's neuropathological changes associated with cognition, brain volume, and plasma biomarkers in patients with repetitive head impacts (RHI)/TES, clinical AD, or typically aging controls. METHODS: We studied 154 participants including 33 with RHI/TES (age 61.5 ± 11.5, 100% male, 11/33 Aß[ +]), 62 with AD and no known prior RHI (age 67.1 ± 10.2, 48% male, 62/62 Aß[ +]), and 59 healthy controls without RHI (HC; age 73.0 ± 6.2, 40% male, 0/59 Aß[ +]). Patients completed neuropsychological testing (memory, executive functioning, language, visuospatial) and structural MRI (voxel-based morphometry analysis), and provided plasma samples analyzed for GFAP, NfL, IL-6, IFN-γ, and YKL-40. For cognition and plasma biomarkers, patients with RHI/TES were stratified as Aß[ +] or Aß[ -] and compared to each other plus the AD and HC groups (ANCOVA adjusting for age and sex). Differences with at least a medium effect size (Cohen's d > 0.50) were interpreted as potentially meaningful. RESULTS: Cognitively, within the TES group, Aß[ +] RHI/TES performed worse than Aß[-] RHI/TES on visuospatial (p = .04, d = 0.86) and memory testing (p = .07, d = 0.74). Comparing voxel-wise brain volume, both Aß[ +] and Aß[ -] RHI/TES had lower medial and anterior temporal lobe volume than HC and did not significantly differ from AD. Comparing plasma biomarkers, Aß[ +] RHI/TES had higher plasma GFAP than HC (p = .01, d = 0.88) and did not significantly differ from AD. Conversely, Aß[ -] RHI/TES had higher NfL than HC (p = .004, d = 0.93) and higher IL-6 than all other groups (p's ≤ .004, d's > 1.0). CONCLUSIONS: Presence of Alzheimer's pathology in patients with RHI/TES is associated with altered cognitive and biomarker profiles. Patients with RHI/TES and positive Aß-PET have cognitive and plasma biomarker changes that are more like patients with AD than patients with Aß[ -] RHI/TES. Measuring well-validated Alzheimer's biomarkers in patients with RHI/TES could improve interpretation of research findings and heighten precision in clinical management.

Association Between Insomnia and Mental Health and Neurocognitive Outcomes Following Traumatic Brain Injury.

We previously described five trajectories of insomnia (each defined by a distinct pattern of insomnia severity over 12 months following traumatic brain injury [TBI]). Our objective in the present study was to estimate the association between insomnia trajectory status and trajectories of mental health and neurocognitive outcomes during the 12 months after TBI. In this study, participants included N = 2022 adults from the Federal Inter-agency Traumatic Brain Injury Repository database and Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. The following outcome measures were assessed serially at 2 weeks, and 3, 6, and 12 months post-injury: Insomnia Severity Index, Patient Health Questionnaire, Post-Traumatic Stress Disorder (PTSD) Checklist for Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), Patient Reported Outcomes Measurement Information System-Pain, and Quality of Life After Brain Injury-Overall Scale. Neurocognitive performance was assessed at 2 weeks, and 6 and 12 months using the Wechsler Adult Intelligence Scales Processing Speed Index and the Trails Making Test Parts A and B. Results indicated that greater insomnia severity was associated with greater abnormality in mental health, quality of life, and neuropsychological testing outcomes. The pattern of insomnia over time tracked the temporal pattern of all these outcomes for all but a very small number of participants. Notably, severe insomnia at 3 or 6 months post-TBI was a risk factor for poor recovery at 12 months post-injury. In conclusion, in this well-characterized sample of individuals with TBI, insomnia severity generally tracked severity of depression, pain, PTSD, quality of life, and neurocognitive outcomes over 12 months post-injury. More intensive sleep assessment is needed to elucidate the nature of these relationships and to help inform best strategies for intervention.

Traumatic Brain Injury and Long-Term Risk of Stroke Among US Military Veterans.

BACKGROUND: Traumatic brain injury (TBI) is associated with significant morbidity, but the association of TBI with long-term stroke risk in diverse populations remains less clear. Our objective was to examine the long-term associations of TBI with stroke and to investigate potential differences by age, sex, race and ethnicity, and time since TBI diagnosis. METHODS: Retrospective cohort study of US military veterans aged 18+ years receiving healthcare in the Veterans Health Administration system between October 1, 2002 and September 30, 2019. Veterans with TBI were matched 1:1 to veterans without TBI on age, sex, race and ethnicity, and index date, yielding 306 796 veterans with TBI and 306 796 veterans without TBI included in the study. In primary analyses, Fine-Gray proportional hazards models adjusted for sociodemographics and medical/psychiatric comorbidities were used to estimate the association between TBI and stroke risk, accounting for the competing risk of mortality. RESULTS: Participants were a mean age of 50 years, 9% were female, and 25% were of non-White race and ethnicity. Overall, 4.7% of veterans developed a stroke over a median follow-up of 5.2 years. Veterans with TBI had 1.69 times (95% CI, 1.64-1.73) increased risk of any stroke (ischemic or hemorrhagic) compared to veterans without TBI. This increased risk was highest in the first-year post-TBI diagnosis (hazard ratio [HR], 2.16 [95% CI, 2.03-2.29]) but remained elevated for 10+ years. Similar patterns were observed for secondary outcomes, with associations of TBI with hemorrhagic stroke (HR, 3.92 [95% CI, 3.59-4.29]) being stronger than with ischemic stroke (HR, 1.56 [95% CI, 1.52-1.61]). Veterans with both mild (HR, 1.47 [95% CI, 1.43-1.52]) and moderate/severe/penetrating injury (HR, 2.02 [95% CI, 1.96-2.09]) had increased risk of stroke compared to veterans without TBI. Associations of TBI with stroke were stronger among older compared to younger individuals (P interaction-by-age<0.001) and were weaker among Black veterans compared to other race and ethnicities (P interaction-by-race<0.001). CONCLUSIONS: Veterans with prior TBI are at increased long-term risk for stroke, suggesting they may be an important population to target for primary stroke prevention measures.