Home, but Homebound After Traumatic Brain Injury: Risk Factors and Associations With Nursing Home Entry and Death.

OBJECTIVE: To examine risk factors associated with homeboundness 1-year after traumatic brain injury (TBI) and to explore associations between homebound status and risk of future mortality and nursing home entry. DESIGN: Secondary analysis of a longitudinal prospective cohort study. SETTING: TBI Model Systems centers. PARTICIPANTS: Community-dwelling TBI Model Systems participants (n=6595) who sustained moderate-to-severe TBI between 2006 and 2016, and resided in a private residence 1-year postinjury. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Homebound status (leaving home ≤1-2d per week), 5-year mortality, and 2- or 5-year nursing home entry. RESULTS: In our sample, 14.2% of individuals were homebound 1-year postinjury, including 2% who never left home. Older age, having less than a bachelor's degree, Medicaid insurance, living in the Northeast or Midwest, dependence on others or special services for transportation, unemployment or retirement, and needing assistance for locomotion, bladder management, and social interactions at 1-year postinjury were associated with being homebound. After adjustment for potential confounders and an inverse probability weight for nonrandom attrition bias, being homebound was associated with a 1.69-times (95% confidence interval, 1.35-2.11) greater risk of 5-year mortality, and a nonsignificant but trending association with nursing home entry by 5 years postinjury (RR=1.90; 95% confidence interval, 0.94-3.87). Associations between homeboundness and mortality were consistent by age subgroup (±65y). CONCLUSIONS: The negative long-term health outcomes among persons with TBI who rarely leave home warrants the need to re-evaluate home discharge as unequivocally positive. The identified risk factors for homebound status, and its associated negative long-term outcomes, should be considered when preparing patients and their families for discharge from acute and postacute rehabilitation care settings. Addressing modifiable risk factors for homeboundness, such as accessible public transportation options and home care to address mobility, could be targets for individual referrals and policy intervention.

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.

The Effects of Repetitive Head Impact Exposure on Mental Health Symptoms Following Traumatic Brain Injury.

OBJECTIVE: This study aimed to characterize the types and timing of repetitive head impact (RHI) exposures in individuals with moderate to severe traumatic brain injury (TBI) and to examine the effects of RHI exposures on mental health outcomes. SETTING: TBI Model Systems National Database. PARTICIPANTS: 447 patients with moderate to severe TBI who reported RHI exposure between 2015 and 2022. DESIGN: Secondary data analysis. MAIN MEASURES: RHI exposures reported on the Ohio State University TBI Identification Method (OSU TBI-ID) were characterized by exposure category, duration, and timing relative to the index TBI. Mental health outcomes were evaluated at the 5-year follow-up assessment using the Patient Health Questionnaire-9 (PHQ-9) for depression symptoms and the Generalized Anxiety Disorder-7 (GAD-7) for anxiety symptoms. RESULTS: The majority of RHI exposures were sports-related (61.1%), followed by other causes (20.8%; including falls), repetitive violence/assault (18.8%), and military exposures (6.7%). Males predominantly reported sports and military exposures, while a larger proportion of females reported violence and falls. Sports exposures were most common before the index TBI, while exposures from falls and violence/abuse were most common after TBI. RHI exposures occurring after the index TBI were associated with higher levels of depression (ß = 5.05; 95% CI, 1.59-8.50) and anxiety (ß = 4.53; 95% CI, 1.02-8.05) symptoms than exposures before the index TBI. CONCLUSION: The findings emphasize the need to consider RHI exposures and their interaction with TBI when assessing mental health outcomes. Understanding the prevalence and challenges associated with RHI post-TBI can inform targeted interventions and improve the well-being of individuals with TBI. Preventive measures and ongoing care should be implemented to address the risks posed by RHI, particularly in individuals with prior TBI, especially surrounding fall and violence/abuse prevention.

Cognitive Performance is Associated With 1-Year Participation and Life Satisfaction Outcomes: A Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To determine, in persons with traumatic brain injury (TBI), the association between cognitive change after inpatient rehabilitation discharge and 1-year participation and life satisfaction outcomes. DESIGN: Secondary analysis of prospectively collected TBI Model Systems (TBIMS) data. SETTING: Inpatient rehabilitation and community. PARTICIPANTS: 499 individuals with TBI requiring inpatient rehabilitation who completed the Brief Test of Adult Cognition by Telephone (BTACT) at inpatient rehabilitation discharge (ie, baseline) and 1-year postinjury. MAIN OUTCOME MEASURES: Participation Assessment with Recombined Tools-Objective (PART-O) and Satisfaction with Life Scale (SWLS). RESULTS: Of 2,840 TBIMS participants with baseline BTACT, 499 met inclusion criteria (mean [standard deviation] age = 45 [19] years; 72% male). Change in BTACT executive function (EF) was not associated with 1-year participation (PART-O; ß = 0.087, 95% CI [-0.004, 0.178], P = .061) when it was the sole model predictor. Change in BTACT episodic memory (EM) was associated with 1-year participation (ß = 0.096, [0.007, 0.184], P = .035), but not after adjusting for demographic, clinical, and functional status covariates (ß = 0.067, 95% CI [-0.010, 0.145], P = .089). Change in BTACT EF was not associated with life satisfaction total scores (SWLS) when it was the sole model predictor (ß = 0.091, 95% CI [-0.001, 0.182], P = .0503). Change in BTACT EM was associated with 1-year life satisfaction before (ß = 0.114, 95% CI [0.025, 0.202], P = .012) and after adjusting for covariates (ß = 0.103, [0.014, 0.191], P = .023). In secondary analyses, change in BTACT EF was associated with PART-O Social Relations and Out and About subdomains before (Social Relations: ß = 0.127, 95% CI [0.036, 0.217], P = .006; Out and About: ß = 0.141, 95% CI [0.051, 0.232], P = .002) and after (Social Relations: ß = 0.168, 95% CI [0.072, 0.265], P < .002; Out and About: ß = 0.156, 95% CI [0.061, 0.252], P < .002) adjusting for functional status and further adjusting for covariates (Social Relations: ß = 0.127, 95% CI [0.040, 0.214], P = .004; Out and About: ß = 0.136, 95% CI [0.043, 0.229], P = .004). However, only the models adjusting for functional status remained significant after multiple comparison correction (ie, Bonferroni-adjusted alpha level = 0.002). CONCLUSION: EF gains during the first year after TBI were related to 1-year social and community participation. Gains in EM were associated with 1-year life satisfaction. These results highlight the potential benefit of cognitive rehabilitation after inpatient rehabilitation discharge and the need for interventions targeting specific cognitive functions that may contribute to participation and life satisfaction after TBI.

The TBI Model Systems Neighborhood Socioeconomic Disadvantage Index (TBIMS-NSDI): Development and Comparison to Individual Socioeconomic Characteristics.

OBJECTIVE: To create a census-based composite neighborhood socioeconomic deprivation index (NSDI) from geocoded residential addresses and to quantify how NSDI aligns with individual-level socioeconomic factors among people with traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: People enrolled in the TBI Model Systems National Database (TBIMS NDB). DESIGN: Secondary analysis of a longitudinal cohort study. MAIN MEASURES: The TBIMS-NSDI was calculated at the census tract level for the United States population based on a principal components analysis of eight census tract-level variables from the American Community Survey. Individual socioeconomic characteristics from the TBIMS NDB were personal household income, education (years), and unemployment status. Neighborhood:Individual NSDI residuals represent the difference between predicted neighborhood disadvantage based on individual socioeconomic characteristics versus observed neighborhood disadvantage based on the TBIMS-NSDI. RESULTS: A single principal component was found to encompass the eight socioeconomic neighborhood-level variables. It was normally distributed across follow-up years 2, 5, and 10 post-injury in the TBIMS NDB. In all years, the TBIMS-NDSI was significantly associated with individual-level measures of household income and education but not unemployment status. Males, persons of Black and Hispanic background, Medicaid recipients, persons with TBI caused by violence, and those living in urban areas, as well as in the Northeast or Southern regions of the United States, were more likely to have greater neighborhood disadvantage than predicted based on their individual socioeconomic characteristics. CONCLUSIONS: The TBIMS-NSDI provides a neighborhood-level indicator of socioeconomic disadvantage, an important social determinant of outcomes from TBI. The Neighborhood:Individual NSDI residual adds another dimension to the TBIMS-NSDI by summarizing how a person's socioeconomic status aligns with their neighborhood socioeconomics. Future studies should evaluate how both measures affect TBI recovery and life quality. Research studying neighborhood socioeconomic disadvantage may improve our understanding of how systemic adversity influences outcomes after TBI.

Predictors of Multidimensional Profiles of Participation After Traumatic Brain Injury: A TBI Model Systems Study.

OBJECTIVES: To identify personal, clinical, and environmental factors associated with 4 previously identified distinct multidimensional participation profiles of individuals following traumatic brain injury (TBI). SETTING: Community. PARTICIPANTS: Participants (n = 408) enrolled in the TBI Model Systems (TBIMS) Participation Module, all 1 year or more postinjury. DESIGN: Secondary data analysis of cross-sectional data from participants in a multicenter TBIMS module study on participation conducted between May 2006 and September 2007. Participants provided responses to questionnaires via a telephone interview at their study follow-up (1, 2, 5, 10, or 15 years postinjury). MAIN MEASURES: Participants provided responses to personal (eg, demographic), clinical (eg, function), environmental (eg, neighborhood type), and participation measures to create multidimensional participation profiles. Data from measures collected at the time of injury (preinjury questionnaire, injury characteristics) were also included. The primary outcome was assignment to one of 4 multidimensional participation profile groups based on participation frequency, importance, satisfaction, and enfranchisement. The measures used to develop the profiles were: Participation Assessment with Recombined Tools-Objective, Importance, and Satisfaction scores, each across 3 domains (Productivity, Social Relationships, Out and About in the Community) and the Enfranchisement Scale (contributing to one's community, feeling valued by the community, choice and control). RESULTS: Results of the multinomial regression analysis, with 4 distinct participation profile groups as the outcome, indicated that education, current employment, current illicit drug use, current driving status, community type, and Functional Independence Measure Cognitive at follow-up significantly distinguished participation profile groups. Findings suggest a trend toward differences in participation profile groups by race/Hispanic ethnicity. CONCLUSIONS: Understanding personal, clinical, and environmental factors associated with distinct participation outcome profiles following TBI may provide more personalized and nuanced guidance to inform rehabilitation intervention planning and/or ongoing clinical monitoring.

Cerebral amyloid angiopathy interacts with neuritic amyloid plaques to promote tau and cognitive decline.

Accumulating data suggest that cerebrovascular disease contributes to Alzheimer's disease pathophysiology and progression toward dementia. Cerebral amyloid angiopathy is a form of cerebrovascular pathology that results from the build-up of ß-amyloid in the vessel walls. Cerebral amyloid angiopathy commonly co-occurs with Alzheimer's disease pathology in the ageing brain and increases the risk of Alzheimer's disease dementia. In the present study, we examined whether cerebral amyloid angiopathy influences tau deposition and cognitive decline independently or synergistically with parenchymal ß-amyloid burden. Secondly, we examined whether tau burden mediates the association between cerebral amyloid angiopathy and cognitive decline. We included data from autopsied subjects recruited from one of three longitudinal clinical-pathological cohort studies: the Rush Memory and Aging Project, the Religious Orders Study and the Minority Aging Research Study. Participants completed annual clinical and cognitive evaluations and underwent brain autopsy. Cerebral amyloid angiopathy pathology was rated as none, mild, moderate or severe. Bielschowsky silver stain was used to visualize neuritic ß-amyloid plaques and neurofibrillary tangles. We used linear regression and linear mixed models to test independent versus interactive associations of cerebral amyloid angiopathy and neuritic plaque burden with tau burden and longitudinal cognitive decline, respectively. We used causal mediation models to examine whether tau mediates the association between cerebral amyloid angiopathy and cognitive decline. The study sample included 1722 autopsied subjects (age at baseline = 80.2 ± 7.1 years; age at death = 89.5 ± 6.7 years; 68% females). Cerebral amyloid angiopathy interacted with neuritic plaques to accelerate tau burden and cognitive decline. Specifically, those with more severe cerebral amyloid angiopathy pathology and higher levels of neuritic plaque burden had greater tau burden and faster cognitive decline. We also found that tau mediated the association between cerebral amyloid angiopathy and cognitive decline among participants with higher neuritic plaque burden. In summary, more severe levels of cerebral amyloid angiopathy and higher parenchymal ß-amyloid burden interacted to promote cognitive decline indirectly via tau deposition. These results highlight the dynamic interplay between cerebral amyloid angiopathy and Alzheimer's disease pathology in accelerating progression toward dementia. These findings have implications for Alzheimer's disease clinical trials and therapeutic development.

Sex-specific effects of microglial activation on Alzheimer's disease proteinopathy in older adults.

Females show a disproportionate burden of Alzheimer's disease pathology and higher Alzheimer's disease dementia prevalences compared to males, yet the mechanisms driving these vulnerabilities are unknown. There is sexual dimorphism in immunological functioning, and neuroimmune processes are implicated in Alzheimer's disease genesis. Using neuropathology indicators from human brain tissue, we examined the mediational role of microglial activation on the relationship between amyloid and tau and how it differs by sex. 187 decedents (64% female; 89 mean age at death; 62% non-demented) from the Rush Memory and Aging Project completed neuropathological evaluations with brain tissue quantified for microglial activation, amyloid-ß and tau. Proportion of morphologically activated microglia was determined via immunohistochemistry (HLA-DP-DQ-DR) and morphological staging (stage I, II or III). Amyloid-ß and tau burden were quantified via immunohistochemistry (M00872 or AT8, respectively). Using causal counterfactual modelling, we estimated the mediational effect of microglial activation on the amyloid-ß to tau relationship in the whole sample and stratified by sex (amyloid-ß â†’ microglial activation → tau). Alternative models tested the role of microglia activation as the precipitating event (microglial activation → amyloid-ß â†’ tau). Microglial activation significantly mediated 33% [95% confidence interval (CI) 10-67] of the relationship between amyloid-ß and tau in the whole sample; stratified analyses suggested this effect was stronger and only statistically significant in females. 57% (95% CI 22-100) of the effect of amyloid-ß on tau was mediated through microglial activation in females, compared to 19% (95% CI 0-64) in males. Regional analyses suggested that mediational effects were driven by greater cortical versus subcortical microglial activation. Relationships were independent of cerebrovascular disease indices. Alternative models suggested that in females, microglial activation was a significant exposure both preceding the amyloid-ß to tau relationship (mediational effect: 50%, 95% CI 23-90) and directly related to tau burden (microglia direct effect: 50%, 95% CI 10-77). By contrast, in males, only the direct effect of microglial activation to tau reached significance (74%, 95% CI 32-100) (mediational effect: 26%, 95% CI 0-68). Our models suggest a reciprocal, bidirectional relationship between amyloid-ß and microglial activation that significantly accounts for tau burden in females. By contrast, in males, direct independent (non-mediational) relationships between microglial activation or amyloid-ß with tau were observed. Microglial activation may be disproportionately important for Alzheimer's disease pathogenesis in females. Determining sex-specific vulnerabilities to Alzheimer's disease development both inform fundamental pathophysiology and support precision health approaches for this heterogeneous disease.

Cognitive Performance, Depression, and Anxiety 1 Year After Traumatic Brain Injury.

OBJECTIVES: To evaluate associations between depression, anxiety, and cognitive impairment among individuals with complicated mild to severe traumatic brain injury (TBI) 1 year after injury. SETTING: Multiple inpatient rehabilitation units across the United States. PARTICIPANTS: A total of 498 adults 16 years and older who completed inpatient rehabilitation for complicated mild to severe TBI. DESIGN: Secondary analysis of a prospective, multicenter, cross-sectional observational cohort study. MAIN MEASURES: Assessments of depression (Traumatic Brain Injury Quality of Life [TBI-QOL] Depression) and anxiety (TBI-QOL Anxiety) as well as a telephone-based brief screening measure of cognitive functioning (Brief Test of Adult Cognition by Telephone [BTACT]). RESULTS: We found an inverse relationship between self-reported depression symptoms and the BTACT Composite score (ß = -0.18, P < .01) and anxiety symptoms and the BTACT Composite score (ß = -0.20, P < .01). There was no evidence this relationship varied by injury severity. Exploratory analyses showed depression and anxiety were negatively correlated with both BTACT Executive Function factor score and BTACT Memory factor score. CONCLUSIONS: Both depression and anxiety have a small but significant negative association with cognitive performance in the context of complicated mild to severe TBI. These findings highlight the importance of considering depression and anxiety when interpreting TBI-related neuropsychological impairments, even among more severe TBI.

Distal and Proximal Predictors of Rehospitalization Over 10 Years Among Survivors of TBI: A National Institute on Disability, Independent Living, and Rehabilitation Research Traumatic Brain Injury Model Systems Study.

OBJECTIVE: To describe the rates and causes of rehospitalization over a 10-year period following a moderate-severe traumatic brain injury (TBI) utilizing the Healthcare Cost and Utilization Project (HCUP) diagnostic coding scheme. SETTING: TBI Model Systems centers. PARTICIPANTS: Individuals 16 years and older with a primary diagnosis of TBI. DESIGN: Prospective cohort study. MAIN MEASURES: Rehospitalization (and reason for rehospitalization) as reported by participants or their proxies during follow-up telephone interviews at 1, 2, 5, and 10 years postinjury. RESULTS: The greatest number of rehospitalizations occurred in the first year postinjury (23.4% of the sample), and the rates of rehospitalization remained stable (21.1%-20.9%) at 2 and 5 years postinjury and then decreased slightly (18.6%) at 10 years postinjury. Reasons for rehospitalization varied over time, but seizure was the most common reason at 1, 2, and 5 years postinjury. Other common reasons were related to need for procedures (eg, craniotomy or craniectomy) or medical comorbid conditions (eg, diseases of the heart, bacterial infections, or fractures). Multivariable logistic regression models showed that Functional Independence Measure (FIM) Motor score at time of discharge from inpatient rehabilitation was consistently associated with rehospitalization at all time points. Other factors associated with future rehospitalization over time included a history of rehospitalization, presence of seizures, need for craniotomy/craniectomy during acute hospitalization, as well as older age and greater physical and mental health comorbidities. CONCLUSION: Using diagnostic codes to characterize reasons for rehospitalization may facilitate identification of baseline (eg, FIM Motor score or craniotomy/craniectomy) and proximal (eg, seizures or prior rehospitalization) factors that are associated with rehospitalization. Information about reasons for rehospitalization can aid healthcare system planning. By identifying those recovering from TBI at a higher risk for rehospitalization, providing closer monitoring may help decrease the healthcare burden by preventing rehospitalization.

Investigation of the association of military employment and Parkinson's disease with a validated Parkinson's disease case-finding strategy.

INTRODUCTION: Persons with military involvement may be more likely to have Parkinson's disease (PD) risk factors. As PD is rare, case finding remains a challenge, contributing to our limited understanding of PD risk factors. Here, we explore the validity of case-finding strategies and whether military employment is associated with PD. MATERIALS AND METHODS: We identified Adult Changes in Thought (ACT) study participants reporting military employment as their longest or second longest occupation. We used self-report and prescription fills to identify PD cases and validated this case-finding approach against medical record review. RESULTS: At enrollment, 6% of 5,125 eligible participants had military employment and 1.8% had prevalent PD; an additional 3.5% developed PD over follow-up (mean: 8.3 years). Sensitivity of our case-finding approach was higher for incident (80%) than prevalent cases (54%). Specificity was high (>97%) for both. Military employment was not associated with prevalent PD. Among nonsmokers, point estimates suggested an increased risk of incident PD with military employment, but the result was non-significant and based on a small number of cases. CONCLUSIONS: Self-report and prescription medications can accurately identify incident PD cases relative to the reference method of medical record review. We found no association between military employment and PD.

Health care utilization and costs in the years preceding dementia identification.

INTRODUCTION: There is evidence that health care utilization increases after incident dementia, particularly after dementia diagnosis and toward the end of life; however, less is known about utilization in the years before dementia identification. METHODS: In this retrospective cohort study we obtained data on n = 5547 beneficiaries from the Health and Retirement Study (HRS)-Medicare linked sample (n = 1241 with and n = 4306 without dementia) to compare longitudinal trends in health care costs and utilization in the 6 years preceding dementia identification relative to a confounder-balanced reference group without dementia. RESULTS: We found that persons with dementia had a greater prevalence of outpatient emergency department (ED), inpatient hospital, skilled nursing, and home health use, and total health care costs in the years preceding dementia identification compared to their similar counterparts without dementia across a comparable timespan in later life. CONCLUSIONS: This study provides evidence to suggest greater healthcare burden may exist well before clinical manifestation and identification of dementia. HIGHLIGHTS: Several studies have documented the tremendous healthcare-related costs of living with dementia, particularly toward the end of life. Dementia is a progressive neurodegenerative disease, which, for some, includes a prolonged pre-clinical phase. However, health services research to date has seldom considered the time before incident dementia. This study documents that health care utilization and costs are significantly elevated in the years before incident dementia relative to a demographically-similar comparison group without dementia.

AD and non-AD mediators of the pathway between the APOE genotype and cognition.

INTRODUCTION: The apolipoprotein E (APOE) genotype is a driver of cognitive decline and dementia. We used causal mediation methods to characterize pathways linking the APOE genotype to late-life cognition through Alzheimer's disease (AD) and non-AD neuropathologies. METHODS: We analyzed autopsy data from 1671 individuals from the Religious Orders Study, Memory and Aging Project, and Minority Aging Research Study (ROS/MAP/MARS) studies with cognitive assessment within 5 years of death and autopsy measures of AD (amyloid beta (Aß), neurofibrillary tangles), vascular (athero/arteriolo-sclerosis, micro-infarcts/macro-infarcts), and non-AD neurodegenerative neuropathologies (TAR DNA protein 43 [TDP-43], Lewy bodies, amyloid angiopathy, hippocampal sclerosis). RESULTS: The detrimental effect of APOE ε4 on cognition was mediated by summary measures of AD and non-AD neurodegenerative neuropathologies but not vascular neuropathologies; effects were strongest in individuals with dementia. The protective effect of APOE ε2 was partly mediated by AD neuropathology and stronger in women than in men. DISCUSSION: The APOE genotype influences cognition and dementia through multiple neuropathological pathways, with implications for different therapeutic strategies targeting people at increased risk for dementia. HIGHLIGHTS: Both apolipoprotein E (APOE) ε2 and APOE ε4 effects on late-life cognition are mediated by AD neuropathology. The estimated mediated effects of most measures of AD neuropathology were similar. Non-Alzheimer's disease (AD) neurodegenerative pathologies mediate the effect of ε4 independently from AD. Non-AD vascular pathologies did not mediate the effect of the APOE genotype on cognition. The protective effect of APOE ε2 on cognition was stronger in women.

Sex differences in associations between APOE ε2 and longitudinal cognitive decline.

INTRODUCTION: We examined whether sex modifies the association between APOE ε2 and cognitive decline in two independent samples. METHODS: We used observational data from cognitively unimpaired non-Hispanic White (NHW) and non-Hispanic Black (NHB) adults. Linear mixed models examined interactive associations of APOE genotype (ε2 or ε4 carrier vs. ε3/ε3) and sex on cognitive decline in NHW and NHB participants separately. RESULTS: In both Sample 1 (N = 9766) and Sample 2 (N = 915), sex modified the association between APOE ε2 and cognitive decline in NHW participants. Specifically, relative to APOE ε3/ε3, APOE ε2 protected against cognitive decline in men but not women. Among APOE ε2 carriers, men had slower decline than women. Among APOE ε3/ε3 carriers, cognitive trajectories did not differ between sexes. There were no sex-specific associations of APOE ε2 with cognition in NHB participants (N = 2010). DISCUSSION: In NHW adults, APOE ε2 may protect men but not women against cognitive decline. HIGHLIGHTS: We studied sex-specific apolipoprotein E (APOE) ε2 effects on cognitive decline. In non-Hispanic White (NHW) adults, APOE ε2 selectively protects men against decline. Among men, APOE ε2 was more protective than APOE ε3/ε3. In women, APOE ε2 was no more protective than APOE ε3/ε3. Among APOE ε2 carriers, men had slower decline than women. There were no sex-specific APOE ε2 effects in non-Hispanic Black (NHB) adults.

Research Letter: Characterization of Older Adults Hospitalized With Traumatic Brain Injury Admitted to Long-Term Acute Care Hospitals.

OBJECTIVE: To describe patient, hospital, and geographic characteristics of older adult Medicare beneficiaries hospitalized with traumatic brain injury (TBI) and admitted to long-term acute care hospitals (LTACHs). SETTING: Acute hospital and LTACH facilities. PARTICIPANTS: In total, 15 148 Medicare beneficiaries 65 years and older with an acute TBI hospitalization who were discharged to an LTACH. DESIGN: This retrospective cohort study used data from Centers for Medicare & Medicaid Services' Medicare Enrollment and Provider Analysis and Review data files from 2011 to 2016. MAIN MEASURES: Patient variables (age, sex, premorbid health burden, medical complications and procedures), hospital variables (for-profit status, bed size), and state/regional geographic variation associated with LTACH TBI admission. RESULTS: Older adult Medicare beneficiaries admitted to LTACH facilities following TBI hospitalization were on average 77.1 years old and predominantly White males. In total, 94.6% of the sample had 2+ multimorbidities present during acute hospitalization. Average acute hospital length of stay of the sample was 19.4 days, and rates of acute mechanical ventilation of any duration and tracheostomy procedures were 56.6% and 40%, respectively. Only 4.1% of patients seen in LTACHs were discharged home after LTACH stay; the primary discharge disposition was skilled nursing facilities (41.3%). Geographic analyses indicated that selected Southern and Midwestern states had the greatest number of LTACH facilities and proportion of LTACH admissions. CONCLUSIONS: There has been limited characterization of the hospitalized TBI population admitted to LTACHs. Our findings among older adult Medicare beneficiaries suggest this population is highly medically complex and are seldom discharged home after their LTACH stay. There are also notable geographic variations in LTACH TBI admissions across the United States. More research is warranted to understand long-term functional outcomes among this population.

Preinjury Health Status of Adults With Traumatic Brain Injury: A Preliminary Matched Case-Control Study.

OBJECTIVE: To discern whether there is evidence that individuals who sustained a traumatic brain injury (TBI) had the greater odds of preexisting health conditions and/or poorer health behaviors than matched controls without TBI. SETTING: Brain Injury Inpatient Rehabilitation Unit at Mount Sinai Hospital. Midlife in the United States (MIDUS) control data were collected via random-digit-dialing phone survey. PARTICIPANTS: TBI cases were enrolled in the TBI Health Study and met at least 1 of the following 4 injury severity criteria: abnormal computed tomography scan; Glasgow Coma Scale score between 3 and 12; loss of consciousness greater than 30 minutes; or post-TBI amnesia longer than 24 hours. Sixty-two TBI cases and 171 matched MIDUS controls were included in the analyses; controls were excluded if they reported having a history of head injury. DESIGN: Matched case-control study. MAIN MEASURES: Self-reported measures of depression symptoms, chronic pain, health status, alcohol use, smoking status, abuse of controlled substances, physical activity, physical health composite score, and behavioral health composite score. RESULTS: Pre-index injury depression was nearly 4 times higher in TBI cases than in matched controls (OR= 3.98, 95% CI, 1.71-9.27; P = .001). We found no significant differences in the odds of self-reporting 3 or more medical health conditions in year prior to index injury (OR = 1.52; 95% CI, 0.82-2.81; P = .183) or reporting more risky health behaviors (OR = 1.48; 95% CI; 0.75-2.91; P = .254]) in individuals with TBI than in controls. CONCLUSION: These preliminary findings suggest that the odds of depression in the year prior to index injury far exceed those reported in matched controls. Further study in larger samples is required to better understand the relative odds of prior health problems in those who sustain a TBI, with a goal of elucidating the implications of preinjury health on post-TBI disease burden.

Health and cognition among adults with and without Traumatic Brain Injury: A matched case-control study.

OBJECTIVES: To evaluate associations between traumatic brain injury (TBI) and presence of health conditions, and to compare associations of health and cognition between TBI cases and controls. METHODS: This matched case-control study used data from the TBI Model Systems National Database (TBI cases) and Midlife in the United States II and Refresher studies (controls).  248 TBI cases were age-, sex-, race-, and education-matched without replacement to three controls. Cases and controls were compared on prevalence of 18 self-reported conditions, self-rated health, composite scores from the Brief Test of Adult Cognition by Telephone. RESULTS: The following conditions were significantly more prevalent among TBI cases versus controls: anxiety/depression (OR = 3.12, 95% CI: 2.20, 4.43, p < .001), chronic sleeping problems (OR = 2.76, 95% CI: 1.86, 4.10, p < .001), headache/migraine (OR = 2.61, 95% CI: 1.50, 4.54, p = .0007), and stroke (OR = 6.42, 95% CI: 2.93, 14.10, p < .001). The relationship between self-rated health and cognition significantly varied by TBI (pinteraction = 0.002). CONCLUSION: Individuals with TBI have greater odds of selected neurobehavioral conditions compared to their demographically similar uninjured peers. Among persons with TBI there was a stronger association between poorer self-rated health and cognition than controls. TBI is increasingly conceptualized as a chronic disease; current findings suggest post-TBI health management requires cognitive supports.

Association of Lifetime TBI and Military Employment with Late Life ADL Functioning: A Population-Based Prospective Cohort Study.

OBJECTIVE: To determine associations of traumatic brain injury (TBI) and military employment with activities of daily living (ADL) in late life. DESIGN: Population-based prospective cohort study with biennial follow-up and censoring at the time of dementia diagnosis. SETTING: Community-based integrated health care delivery system. PARTICIPANTS: Participants (N=4953) were men (n=2066) and women (n=2887) aged ≥65 years who were dementia free. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: ADL difficulties at baseline and accumulation during follow-up. RESULTS: TBI with loss of consciousness (LOC) before the age of 40 years was associated with slightly higher ADL difficulty at baseline for women (rate ratio [RR], 1.44; 95% confidence interval [CI], 1.08-1.93; P=.01). For men, TBI with LOC at any age was associated with greater ADL difficulty at baseline (age <40y: RR, 1.58; 95% CI, 1.20-2.08; P=.001; age ≥40y: RR, 2.14; 95% CI, 1.24-3.68; P=.006). TBI with LOC was not associated with the rate of accumulation of ADL difficulties over time in men or women. There was no evidence of an association between military employment and either outcome, nor of an interaction between military employment and TBI with LOC. Findings were consistent across a variety of sensitivity analyses. CONCLUSIONS: Further investigation into factors underlying greater late life functional impairment among survivors of TBI is warranted.

Reinjury After Moderate to Severe TBI: Rates and Risk Factors in the NIDILRR Traumatic Brain Injury Model Systems.

OBJECTIVES: To compare characteristics of those who do and do not sustain subsequent traumatic brain injuries (TBIs) following index TBI and to identify reinjury risk factors. DESIGN: Secondary data analysis of an ongoing longitudinal cohort study. SETTING: TBI Model Systems Centers. PARTICIPANTS: In total, 11 353 individuals aged 16+ years. MAIN OUTCOME MEASURES: Ohio State University TBI Identification Method. RESULTS: In total, 7.9% of individuals reported sustaining a TBI post-index TBI. Twenty percent of reinjuries occurred within a year of the index TBI. Reinjury risk followed an approximate U-shaped distribution such that risk was higher in the first year, declined 2 to 10 years postinjury, and then increased after 10 years. A multivariable Weibull model identified predictors of reinjury: younger (<29 years) and middle-aged and older (50+ years) age at index TBI relative to middle age, pre-index TBI, pre-index alcohol and illicit drug use, incarceration history, and less severe index TBI. CONCLUSIONS: A subset of individuals who receive inpatient rehabilitation for TBI are at an increased risk for reinjury, and an injury-prone phenotype may be characterized by engagement in risk behaviors. Factors associated with reinjury risk may differ for younger versus middle-aged and older adults. Findings underscore the need for empirically informed risk stratification models to identify TBI survivors at risk for reinjury.

Research Letter: Performance of the Brief Test of Adult Cognition by Telephone in a National Sample.

OBJECTIVE: To create a larger, more representative community comparison sample of the Brief Test of Adult Cognition by Telephone (BTACT) data to facilitate assessment of cognitive function in research studies. SETTING: National US community-based survey. PARTICIPANTS: In total, 6747 healthy adults aged 23 to 84 years (53% female; mean age = 55 years, SD = 13). DESIGN: Secondary data analysis of BTACT data collected from the National Survey of Midlife Development in the United States (MIDUS) II and MIDUS Refresher cohorts. MAIN MEASURES: The BTACT, a brief (15-20 minute) measure of global cognitive function validated for telephone administration. RESULTS: This article provides BTACT community comparison sample data based on age, sex, and education from a national sample. Similar to other cognitive measures, BTACT scores decreased with age and increased with education. CONCLUSIONS: The BTACT community comparison sample will facilitate investigation of cognitive functioning in large-scale traumatic brain injury research studies and will support secondary analysis of existing BTACT data gathered through the MIDUS study.