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Traumatic brain injury (TBI) is an established risk factor for dementia. However, the magnitude of risk is highly variable across studies. Identification of sub-populations at highest risk, with careful consideration of potential sources of bias, is urgently needed to guide public health policy and research into mechanisms and treatments. We conducted a systematic review and meta-analysis of risk of all-cause dementia after all-severity TBI. We assessed for effect of participant age and sex, veteran status, research methods, and region. The search window covered January 1990 to January 2019. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines. Thirty-two studies met inclusion criteria. Data were pooled using random effects models. Population attributable risk (PAR) of dementia due to TBI in the U.S. was calculated by sex and veteran status. Pooled risk ratio (RR) for dementia after TBI was 1.66 (95% confidence interval 1.42-1.93). Younger age, male sex, and studies from Asia were associated with significantly higher risk; veteran status was not. Risk of dementia associated with "head injury/trauma" was not significantly different from that associated with "TBI" diagnosis specifically. PAR of dementia due to TBI among U.S. veterans was twice that of the general U.S. population, largely due to the high prevalence of TBI exposure in the majority male veteran population. This meta-analysis found that TBI is associated with nearly 70% increased risk of dementia. Risk may be highest among younger adults, men, and cohorts in Asia. Efforts to prevent TBI and also to prevent post-TBI dementia are of high importance. Additionally, improved methods for diagnosing and tracking TBI on a public health level, such as national registries, may improve the quality and generalizability of future epidemiological studies investigating the association between TBI and dementia.

Traumatic brain injury (TBI) is common among older adults as well as among veterans in the United States and can increase risk for dementia. We compared prevalence of TBI in older male veterans and civilians using a nationally representative sample. We examined data from 599 male respondents to the 2014 wave of the Health and Retirement Study (HRS), a nationally representative survey of older adults, randomly selected to participate in a comprehensive TBI survey. Respondents self-reported no injury, non-TBI head/neck injury (NTI), or TBI. We used weighted analyses to examine prevalence of injury and relative risk of injury subtypes. Among male veterans, we found a national prevalence of more than 70% for lifetime history of any head/neck injury (TBI plus NTI), 14.3% for multiple NTI, and 36% for lifetime history of at least one TBI. In contrast, prevalence estimates for male civilians were 58% for lifetime history of head/neck injury, 4.8% for multiple NTI, and 45% for lifetime history of at least one TBI (all comparisons, p  < 0.001). Male civilians have higher self-reported TBI prevalence, whereas male veterans have higher self-reported NTI and multiple-NTI prevalence. Further research on drivers of the unexpectedly higher prevalence of lifetime history of TBI in male civilians, as well as on mechanisms and sequelae of the highly prevalent non-TBI head/neck injuries among older male veterans, is warranted.

Objectives: 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., Participants: 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)., Design: Cross-sectional survey study., Main Measures: 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., Analyses: 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., Results: 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., Conclusion: 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.

Background: Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD., Methods: Residents of East Liverpool (n=83) and Marietta, OH (n=99) exposed to chronic (>10years) environmental Mn through industrial pollution were administered neuropsychological measures and a physician-rated scale of movement-disorder symptoms. Two-step cluster analysis was used to group residents based on tremor symptoms, bradykinesia/rigidity symptoms, gait disturbance, and executive function. Cluster membership was validated using modeled air-Mn exposure and a computerized tremor measure., Results: Elevated tremor and motor symptoms and executive dysfunction were observed, and TD and NTD symptom clusters were identified. Two additional clusters were also identified: Executive Dysfunction and Normal Functioning. The NTD residents, with elevated levels of gait disturbance and other movement disorder symptoms, did not evidence EF impairment, as predicted. Instead, residents with EF impairment formed their own cluster, and were relatively free of movement disorder symptoms., Conclusions: Results resemble reports in the PD literature with TD and NTD clusters identified, but executive dysfunction did not cluster with NTD symptoms. PD and Mn exposure likely have differing pathophysiology and developmental courses, and therefore different symptom patterns, even when similar symptoms are present., (Published by Elsevier B.V.)

Background: After the 9/11/2001 World Trade Center (WTC) attack, many police-responders developed PTSD and might be vulnerable to develop depression and/or anxiety. Comorbidity of PTSD, depression, and/or anxiety is examined., Method: Police enrollees (N = 1,884) from the WTC Health Registry were categorized into four groups based on comorbidity of PTSD, depression, and anxiety. DSM-IV diagnostic criteria for PTSD were used. Depression (PHQ-8) and anxiety (GAD-7) were assessed with standardized psychometric inventories. Multinomial logistic regression was used to identify putative risk factors associated with comorbidity of PTSD., Results: Of 243 (12.9% of total) police with probable PTSD, 21.8% had probable PTSD without comorbidity, 24.7% had depression, 5.8% had anxiety, and 47.7% had comorbid depression and anxiety. Risk factors for comorbid PTSD, depression, and anxiety include being Hispanic, decrease in income, experiencing physical injury on 9/11, experiencing stressful/traumatic events since 9/11, and being unemployed/retired., Conclusion: Nearly half of police with probable PTSD had comorbid depression and anxiety. Am. J. Ind. Med. 59:425-436, 2016. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Manganese (Mn) inhalation has been associated with neuropsychological and neurological sequelae in exposed workers. Few environmental epidemiologic studies have examined the potentially neurotoxic effects of Mn exposure in ambient air on motor function and hand tremor in adult community residents. Mn exposed residents were recruited in two Ohio towns: Marietta, a town near a ferro-manganese smelter, and East Liverpool, a town adjacent to a facility processing, crushing, screening, and packaging Mn products., Methods: Chronic (≥ 10 years) exposure to ambient air Mn in adult residents and effects on neuropsychological and neurological outcomes were investigated. Participants from Marietta (n=100) and East Liverpool (n=86) were combined for analyses. AERMOD dispersion modeling of fixed-site outdoor air monitoring data estimated Mn inhalation over a ten year period. Adult Mn-exposed residents' psychomotor ability was assessed using Finger Tapping, Hand Dynamometer, Grooved Pegboard, and the Computerized Adaptive Testing System (CATSYS) Tremor system. Bayesian structural equation modeling was used to assess associations between air-Mn and motor function and tremor., Results: Air-Mn exposure was significantly correlated in bivariate analyses with the tremor test (CATSYS) for intensity, center frequency and harmonic index. The Bayesian path analysis model showed associations of air-Mn with the CATSYS non-dominant center frequency and harmonic index; while the Bayesian structural equation model revealed associations between air-Mn and lower Finger Tapping scores. Household income was significantly associated with motor dysfunction but not with tremor., Conclusion: Tremor and motor function were associated with higher exposure to airborne Mn., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Manganese (Mn), an essential element, can be neurotoxic in high doses. This cross-sectional study explored the cognitive function of adults residing in two towns (Marietta and East Liverpool, Ohio, USA) identified as having high levels of environmental airborne Mn from industrial sources. Air-Mn site surface emissions method modeling for total suspended particulate (TSP) ranged from 0.03 to 1.61 μg/m(3) in Marietta and 0.01-6.32 μg/m(3) in East Liverpool. A comprehensive screening test battery of cognitive function, including the domains of abstract thinking, attention/concentration, executive function and memory was administered. The mean age of the participants was 56 years (±10.8 years). Participants were mostly female (59.1) and primarily white (94.6%). Significant relationships (p<0.05) were found between Mn exposure and performance on working and visuospatial memory (e.g., Rey-O Immediate β=-0.19, Rey-O Delayed β=-0.16) and verbal skills (e.g., Similarities β=-0.19). Using extensive cognitive testing and computer modeling of 10-plus years of measured air monitoring data, this study suggests that long-term environmental exposure to high levels of air-Mn, the exposure metric of this paper, may result in mild deficits of cognitive function in adult populations., (Copyright © 2015 Elsevier Inc. All rights reserved.)