Change in Enlarged Perivascular Spaces over Time and Associations with Outcomes After Traumatic Brain Injury.

Enlarged perivascular spaces (EPVs) can be seen on magnetic resonance imaging (MRI) scans in various neurological diseases, including traumatic brain injury (TBI). EPVs have been associated with cognitive dysfunction and sleep disturbances; however, their clinical significance remains unclear. The goal of this study was to identify MRI burden of EPVs over time following TBI and to explore their relationship with postinjury outcomes. Individuals with TBI underwent postinjury data collection at Day 1 (blood), 2 weeks (blood, MRI, outcomes), and 6 months (blood, MRI, outcomes). EPV burden was assessed using T1 and FLAIR sequences on representative slices in the centrum semiovale, basal ganglia, and midbrain. Serum blood was assayed to measure concentrations of neurofilament light (NfL) and glial fibrillary acidic protein (GFAP). Thirty-two participants with TBI were included (mean age 36.8 years, 78% male, 50% White). Total EPVs count did not significantly change from 2 weeks (23.5 [95% confidence interval or CI = 22.0-32.0]) to 6 months (26.0 [95% CI = 22.0-30.0], p = 0.16). For self-reported measures of sleep, there were no significant associations between EPVs count and Insomnia Severity Index (2 weeks: ß = -0.004; 95% CI = -0.094, 0.086; 6 months: ß = 0.002; 95% CI = -0.122, 0.125) or the subset of sleep questions on the Rivermead Post-Concussion Symptoms Questionnaire (2 weeks: ß = -0.005; 95% CI = -0.049, 0.039; 6 months: ß = -0.019; 95% CI = -0.079, 0.042). Functional outcome, determined by 6 months incomplete recovery (Glasgow Outcome Scale-Extended [GOS-E < 8]) versus complete recovery (GOS-E = 8), was significantly associated with a higher number of EPVs at 2 weeks (odds ratio = 0.94, 95% CI = 0.88-0.99). Spearman correlations showed no significant relationship between EPVs count and GFAP or NfL. This study used commonly acquired MRI sequences to quantify EPVs and investigated their utility as a potential imaging biomarker in TBI. Given the minimal change in EPVs over time, this period may not be long enough for potential recovery or may indicate that EPVs are structural findings that do not significantly change over time.

Associations of Neighborhood Environments and Socioeconomic Status With Subclinical Atherosclerosis: An Integrative Review.

BACKGROUND: A limited understanding exists on the associations of neighborhood environment with subclinical atherosclerosis and its progression. PURPOSE: The purpose of this integrative review was to explore associations of neighborhood environments and socioeconomic status (SES) with subclinical atherosclerosis and its long-term progression. RESULTS: Three themes were identified: environmental exposure affects the natural history of atherosclerosis, neighborhood characteristics are associated with subclinical atherosclerosis, and individual SES is associated with development and progression of subclinical atherosclerosis more so than neighborhood SES. Some variations in results were noted based on the vascular site examined. CLINICAL IMPLICATIONS: Disadvantaged neighborhoods and low SES are associated with greater subclinical atherosclerosis. Inconsistencies in a few studies seemed to be related to lack of coronary artery progression among the relatively young adults. This suggests further examination is needed of the contextual associations of neighborhood and SES with markers of generalized atherosclerosis, such as carotid intima-media thickness.

Correlations of Socioeconomic and Clinical Determinants with United States County-Level Stroke Prevalence.

Socioeconomic status (SES) is a multi-faceted theoretical construct associated with stroke risk and outcomes. Knowing which SES measures best correlate with population stroke metrics would improve its accounting in observational research and inform interventions. Using the Centers for Disease Control and Prevention's (CDC) Population Level Analysis and Community Estimates (PLACES) and other publicly available databases, we conducted an ecological study comparing correlations of different United States county-level SES, health care access and clinical risk factor measures with age-adjusted stroke prevalence. The prevalence of adults living below 150% of the federal poverty level most strongly correlated with stroke prevalence compared to other SES and non-SES measures (correlation coefficient = 0.908, R2 = 0.825; adjusted partial correlation coefficient: 0.589, R2 = 0.347). ANN NEUROL 2024.

Associations of Sex and Sport Contact-Level with Recovery Timelines Among Collegiate Athletes with Sport-Related Concussion.

BACKGROUND: Growing interest has motivated recent studies to examine differences in recovery after sport-related concussion (SRC) by sex. However, heterogeneity in study design, participants, and recovery outcomes has led to mixed findings. Further work is needed to evaluate potential differences by sex and to investigate the role of related characteristics, such as sport contact-level, in recovery timelines. This study aimed to investigate whether concussion recovery trajectories differ by sex, considering a priori clinical and demographic covariates, and accounting for the sequence of recovery outcomes. Our secondary question was whether sport contact-level modifies the relationship between sex and time to outcomes. Using data from the Ivy League-Big Ten Epidemiology of Concussion Study, we included SRCs reported across five academic years; 2015-2020 (February 2020). We used Cox proportional hazards regressions to estimate associations between sex and time from injury to three outcomes: (1) symptom resolution, (2) return to academics, (3) return to full play, accounting for measured confounders. RESULTS: Among 1160 SRCs (male, n = 667; female, n = 493) with complete data, median age overall was 20 years (25th-75th percentiles:19-21), and most occurred among athletes playing high-contact sports (78.0%). Males were slightly more likely to complete symptom resolution over time compared to females (HR = 1.18, 95%CI = 1.05-1.33), but results were attenuated in fully adjusted models (HR 1.13, 95%CI = 0.99-1.29). Similarly, the HR of full academic return for males compared to females was 1.22 (95%CI = 1.07-1.38), but was attenuated in fully adjusted models (HR = 1.11, 95%CI = 0.97-1.28). The HR of full return to play for males compared to females was 1.14 (95%CI = 1.02-1.28), and was attenuated after adjustment (HR = 1.06, 95%CI = 0.93-1.20) as well. The interaction between sex and playing a high/low-contact sport was not statistically significant across models, though differences were apparent. CONCLUSIONS: Among a cohort of collegiate athletes with SRC, recovery timelines appeared similar between male and female athletes, adjusting for measured confounders. Differences by sex, considering sport contact-level, were evident and may be important clinically and in future studies. This study used robust methods, accounting for nesting in the sequence of RTP outcomes. Results inform concussion management protocols and planned qualitative work to further elucidate how collegiate athletes experience concussion recovery. KEY POINTS: Heterogeneity in study design, participants, and recovery outcomes has led to mixed findings in determining differences in recovery trajectories after concussion by sex. We found that having longer time to symptom resolution, and also the sequence of having academic return before symptoms resolve and longer time to academic return were confounders in the relationship between sex and RTP timelines. Time to sequential recovery outcomes appeared similar between male and female athletes, adjusting for observable confounders. Further differences by sex were evident when considering contact-level, and may be important to consider clinically and in future research. Results indicate that differences in concussion recovery trajectories by sex may be largely attributed to and driven by differences in sports with a men's or women's team only, such as football, and this should be explored further.

Traumatic brain injury and cognitive change over 30 years among community-dwelling older adults.

INTRODUCTION: There is limited evidence regarding the rate of long-term cognitive decline after traumatic brain injury (TBI) among older adults. METHODS: In this prospective cohort study, time-varying TBI was defined by self-report and International Classification of Disease diagnostic codes. Cognitive testing was performed at five visits over 30 years and scores were combined into a global cognition factor score. Adjusted linear mixed-effects models estimated the association of TBI with cognitive change. RESULTS: A total of 11,701 Atherosclerosis Risk in Communities (ARIC) Study participants (mean baseline age 58 years, 58% female, 25% Black) without TBI at baseline were included. Over follow-up, 18% experienced TBI. The adjusted average decline in cognition per decade (standard deviation units) was more than twice as fast among individuals with ≥ 2 incident TBIs (𝛽 = -0.158, 95% confidence interval [CI] = -0.253,-0.063), but not among individuals with 1 TBI (𝛽 = -0.052, 95% CI = -0.107, 0.002), compared to without TBI (𝛽 = -0.057, 95% CI = -0.095, -0.020). DISCUSSION: This study provides robust evidence that TBIs fundamentally alter the trajectories of cognitive decline. HIGHLIGHTS: The adjusted average decline in cognition per decade (standard deviation units) was more than twice as fast among individuals with ≥ 2 incident traumatic brain injuries (TBIs; 𝛽 = -0.158, 95% confidence interval [CI] = -0.253, -0.063), but not with 1 TBI (𝛽 = -0.052, 95% CI = -0.107, 0.002), compared to without TBI (𝛽 = -0.057, 95% CI = -0.095, -0.020). Over a period of 30 years, this difference in cognitive decline is equivalent to individuals with ≥ 2 TBIs being 9.7 years older at baseline. Associations of TBI were stronger among individuals with one or two apolipoprotein E (APOE) ε4 alleles than among individuals with zero APOE ε4 alleles (P interaction = 0.007).

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.

Derivation and Validation of ICD-10 Codes for Identifying Incident Stroke.

Importance: Claims data with International Statistical Classification of Diseases, Tenth Revision (ICD-10) codes are routinely used in clinical research. However, the use of ICD-10 codes to define incident stroke has not been validated against expert-adjudicated outcomes in the US population. Objective: To develop and validate the accuracy of an ICD-10 code list to detect incident stroke events using Medicare inpatient fee-for-service claims data. Design, Setting, and Participants: This cohort study used data from 2 prospective population-based cohort studies, the Atherosclerosis Risk in Communities (ARIC) study and the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, and included participants aged 65 years or older without prior stroke who had linked Medicare claims data. Stroke events in the ARIC and REGARDS studies were identified via active surveillance and adjudicated by expert review. Medicare-linked ARIC data (2016-2018) were used to develop a list of ICD-10 codes for incident stroke detection. The list was validated using Medicare-linked REGARDS data (2016-2019). Data were analyzed from September 1, 2022, through September 30, 2023. Exposures: Stroke events detected in Medicare claims vs expert-adjudicated stroke events in the ARIC and REGARDS studies. Main Outcomes and Measures: The main outcomes were sensitivity and specificity of incident stroke detection using ICD-10 codes. Results: In the ARIC study, there were 110 adjudicated incident stroke events among 5194 participants (mean [SD] age, 80.1 [5.3] years) over a median follow-up of 3.0 (range, 0.003-3.0) years. Most ARIC participants were women (3160 [60.8%]); 993 (19.1%) were Black and 4180 (80.5%) were White. Using the primary diagnosis code on a Medicare billing claim, the ICD-10 code list had a sensitivity of 81.8% (95% CI, 73.3%-88.5%) and a specificity of 99.1% (95% CI, 98.8%-99.3%) to detect incident stroke. Using any diagnosis code on a Medicare billing claim, the sensitivity was 94.5% (95% CI, 88.5%-98.0%) and the specificity was 98.4% (95% CI, 98.0%-98.8%). In the REGARDS study, there were 140 adjudicated incident strokes among 6359 participants (mean [SD] age, 75.8 [7.0] years) over a median follow-up of 4.0 (range, 0-4.0) years. More than half of the REGARDS participants were women (3351 [52.7%]); 1774 (27.9%) were Black and 4585 (72.1%) were White. For the primary diagnosis code, the ICD-10 code list had a sensitivity of 70.7% (95% CI, 63.2%-78.3%) and a specificity of 99.1% (95% CI, 98.9%-99.4%). For any diagnosis code, the ICD-10 code list had a sensitivity of 77.9% (95% CI, 71.0%-84.7%) and a specificity of 98.9% (95% CI, 98.6%-99.2%). Conclusions and Relevance: These findings suggest that ICD-10 codes could be used to identify incident stroke events in Medicare claims with moderate sensitivity and high specificity.

Head Injury and Risk of Incident Ischemic Stroke in Community-Dwelling Adults.

BACKGROUND: While stroke is a recognized short-term sequela of traumatic brain injury, evidence about long-term ischemic stroke risk after traumatic brain injury remains limited. METHODS: The Atherosclerosis Risk in Communities Study is an ongoing prospective cohort comprised of US community-dwelling adults enrolled in 1987 to 1989 followed through 2019. Head injury was defined using self-report and hospital-based diagnostic codes and was analyzed as a time-varying exposure. Incident ischemic stroke events were physician-adjudicated. We used Cox regression adjusted for sociodemographic and cardiovascular risk factors to estimate the hazard of ischemic stroke as a function of head injury. Secondary analyses explored the number and severity of head injuries; the mechanism and severity of incident ischemic stroke; and heterogeneity within subgroups defined by race, sex, and age. RESULTS: Our analysis included 12 813 participants with no prior head injury or stroke. The median follow-up age was 27.1 years (25th-75th percentile=21.1-30.5). Participants were of median age 54 years (25th-75th percentile=49-59) at baseline; 57.7% were female and 27.8% were Black. There were 2158 (16.8%) participants with at least 1 head injury and 1141 (8.9%) participants with an incident ischemic stroke during follow-up. For those with head injuries, the median age to ischemic stroke was 7.5 years (25th-75th percentile=2.2-14.0). In adjusted models, head injury was associated with an increased hazard of incident ischemic stroke (hazard ratio [HR], 1.34 [95% CI, 1.12-1.60]). We observed evidence of dose-response for the number of head injuries (1: HR, 1.16 [95% CI, 0.97-1.40]; ≥2: HR, 1.94 [95% CI, 1.39-2.71]) but not for injury severity. We observed evidence of stronger associations between head injury and more severe stroke (National Institutes of Health Stroke Scale score ≤5: HR, 1.31 [95% CI, 1.04-1.64]; National Institutes of Health Stroke Scale score 6-10: HR, 1.64 [95% CI, 1.06-2.52]; National Institutes of Health Stroke Scale score ≥11: HR, 1.80 [95% CI, 1.18-2.76]). Results were similar across stroke mechanism and within strata of race, sex, and age. CONCLUSIONS: In this community-based cohort, head injury was associated with subsequent ischemic stroke. These results suggest the importance of public health interventions aimed at preventing head injuries and primary stroke prevention among individuals with prior traumatic brain injuries.

Epidemiology of fractures in adults of African ancestry with diabetes mellitus: A systematic review and meta-analysis.

Diabetes mellitus (DM) is associated with increased fracture risk in White adults. However, the impact of DM on fractures in Black adults is unknown. This systematic review and meta-analysis investigated the association between DM and fractures in adults of African ancestry. MEDLINE, Scopus, CINAHL and Embase databases were searched from their inception up to November 2023 for all studies in the English language investigating the epidemiology of fractures (prevalence, incidence, or risk) in Black men and women (age ≥ 18 years) with type 1 or type 2 DM. Effect sizes for prevalence of previous fractures (%) and incident fracture risk (hazard ratio [HR]) were calculated using a random-effects model on Stata (version 18.0). There were 13 eligible studies, of which 12 were conducted in Black adults from the United States, while one was conducted in adults of West African ancestry from Trinidad and Tobago. We found no fracture data in Black adults with DM living in Africa. Five studies were included in a meta-analysis of incident fracture risk, reporting data from 2926 Black and 6531 White adults with DM. There was increased risk of fractures in Black adults with DM compared to non-DM (HR = 1.65; 95 % confidence interval [CI]: 1.14, 2.39). The risk of fractures was also higher in White adults with DM compared to non-DM (HR = 1.31; 95 % CI: 1.06, 1.61) among these studies. Five studies were included in a meta-analysis of fracture prevalence, of which three also reported fracture prevalence in White adults. There were 175 previous fractures among 993 Black adults with DM and 384 previous fractures among 1467 White adults with DM, with a pooled prevalence of 17.5 % (95 % CI: 15.4, 19.6) and 25.8 % (95 % CI: 4.8, 46.8), respectively. Our results indicate a high burden of fractures in Black adults with DM.

Sex differences in the extent of acute axonal pathologies after experimental concussion.

Although human females appear be at a higher risk of concussion and suffer worse outcomes than males, underlying mechanisms remain unclear. With increasing recognition that damage to white matter axons is a key pathologic substrate of concussion, we used a clinically relevant swine model of concussion to explore potential sex differences in the extent of axonal pathologies. At 24 h post-injury, female swine displayed a greater number of swollen axonal profiles and more widespread loss of axonal sodium channels than males. Axon degeneration for both sexes appeared to be related to individual axon architecture, reflected by a selective loss of small caliber axons after concussion. However, female brains had a higher percentage of small caliber axons, leading to more extensive axon loss after injury compared to males. Accordingly, sexual dimorphism in axonal size is associated with more extensive axonal pathology in females after concussion, which may contribute to worse outcomes.

Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study.

INTRODUCTION: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. METHODS: Current or most recent occupation at ARIC baseline (1987-1989; aged 45-64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999-2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990-1992) to visit 5 (2011-2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. RESULTS: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition. CONCLUSION: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences.

Posttraumatic Epilepsy and Dementia Risk.

Importance: Although both head injury and epilepsy are associated with long-term dementia risk, posttraumatic epilepsy (PTE) has only been evaluated in association with short-term cognitive outcomes. Objective: To investigate associations of PTE with dementia risk. Design, Setting, and Participants: The Atherosclerosis Risk in Communities (ARIC) study initially enrolled participants from 1987 to 1989 and this prospective cohort study uses data through December 31, 2019, with a median follow-up of 25 years. Data were analyzed between March 14, 2023, and January 2, 2024. The study took place in 4 US communities in Minnesota, Maryland, North Carolina, and Mississippi. Of 15 792 ARIC study participants initially enrolled, 2061 were ineligible and 1173 were excluded for missing data, resulting in 12 558 included participants. Exposures: Head injury was defined by self-report and International Classification of Diseases (ICD) diagnostic codes. Seizure/epilepsy was defined using ICD codes. PTE was defined as a diagnosis of seizure/epilepsy occurring more than 7 days after head injury. Head injury, seizure/epilepsy, and PTE were analyzed as time-varying exposures. Main Outcomes and Measures: Dementia was defined using cognitive assessments, informant interviews, and ICD and death certificate codes. Adjusted Cox and Fine and Gray proportional hazards models were used to estimate dementia risk. Results: Participants had a mean (SD) age of 54.3 (5.8) years at baseline, 57.7% were female, 28.2% were of self-reported Black race, 14.4% were ultimately categorized as having head injury, 5.1% as having seizure/epilepsy, and 1.2% as having PTE. Over a median follow-up of 25 (25th to 75th percentile, 17-30) years, 19.9% developed dementia. In fully adjusted models, compared with no head injury and no seizure/epilepsy, PTE was associated with 4.56 (95% CI, 4.49-5.95) times the risk of dementia, while seizure/epilepsy was associated with 2.61 (95% CI, 2.21-3.07) times the risk and head injury with 1.63 (95% CI, 1.47-1.80) times the risk. The risk of dementia associated with PTE was significantly higher than the risk associated with head injury alone and with nontraumatic seizure/epilepsy alone. Results were slightly attenuated in models accounting for the competing risks of mortality and stroke, but patterns of association remained similar. In secondary analyses, the increased dementia risk associated with PTE occurring after first vs second head injury and after mild vs moderate/severe injury was similar. Conclusions and Relevance: In this community-based cohort, there was an increased risk of dementia associated with PTE that was significantly higher than the risk associated with head injury or seizure/epilepsy alone. These findings provide evidence that PTE is associated with long-term outcomes and supports both the prevention of head injuries via public health measures and further research into the underlying mechanisms and the risk factors for the development of PTE, so that efforts can also be focused on the prevention of PTE after a head injury.

Stroke Subtype and Risk of Subsequent Hospitalization: The Atherosclerosis Risk in Communities Study

BACKGROUND AND OBJECTIVES: Risk of readmission after stroke differs by stroke (sub)type and etiology, with higher risks reported for hemorrhagic stroke and cardioembolic stroke. We examined the risk and cause of first readmission by stroke subtype over the years post incident stroke. METHODS: Atherosclerosis Risk in Communities (ARIC) study participants (n = 1,412) with first-ever stroke were followed up for all-cause readmission after incident stroke. Risk of first readmission was examined by stroke subtypes (cardioembolic, thrombotic/lacunar, and hemorrhagic [intracerebral and subarachnoid]) using Cox and Fine-Gray proportional hazards models, adjusting for sociodemographic and cardiometabolic risk factors. RESULTS: Among 1,412 participants (mean [SD] age 72.4 [9.3] years, 52.1% women, 35.3% Black), 1,143 hospitalizations occurred over 41,849 person-months. Overall, 81% of participants were hospitalized over a maximum of 26.6 years of follow-up (83% of participants with thrombotic/lacunar stroke, 77% of participants with cardioembolic stroke, and 78% of participants with hemorrhagic stroke). Primary cardiovascular and cerebrovascular diagnoses were reported for half of readmissions. Over the entire follow-up period, compared with cardioembolic stroke, readmission risk was lower for thrombotic/lacunar stroke (hazard ratio [HR] 0.82, 95% CI 0.71-0.95) and hemorrhagic stroke (HR 0.74, 95% CI 0.58-0.93) in adjusted Cox proportional hazards models. By contrast, there was no statistically significant difference among subtypes when adjusting for atrial fibrillation and competing risk of death. Compared with cardioembolic stroke, thrombotic/lacunar stroke was associated with lower readmission risk within 1 month (HR 0.66, 95% CI 0.46-0.93) and during 1 month-1 year (HR 0.78, 95% CI 0.62-0.97), and hemorrhagic stroke was associated with lower risk during 1 month-1 year (HR 0.60, 95% CI 0.41-0.87). There was no significant difference between subtypes in readmission risk during later periods. DISCUSSION: Over 26 years of follow-up, 81% of stroke participants experienced a readmission. Cardiovascular and cerebrovascular diagnoses at readmission were most common across stroke subtypes. Though cardioembolic stroke has previously been reported to confer higher risk of readmission, in this study, the readmission risk was not statistically significantly different between stroke subtypes or over different periods when accounting for the competing risk of death.

Associations Between Prior Head Injury, Physical Functioning, and Frailty in the Atherosclerosis Risk in Communities Study.

BACKGROUND: Older adults have the highest rates of head injury and are at the greatest risk for subsequent dysfunction, yet research on subsequent physical decline is limited. We sought to examine cross-sectional and prospective associations of head injury with physical functioning and frailty among older adults. METHODS: A total of 5 598 Atherosclerosis Risk in Communities Study participants from Visit 5 (2011-13) underwent assessments of physical functioning (Short Physical Performance Battery [SPPB], comprised of gait speed, chair stands, and balance) and frailty (defined using established criteria) were followed through Visit 7 (2018-19). Head injury was self-reported or based on ICD-9 codes. Adjusted linear and multinomial logistic regression models were used to estimate associations. Prospective models incorporated inverse probability of attrition weights to account for death or attrition. RESULTS: Participants were a mean age of 75 years, 58% were women, 22% were Black, and 27% had a prior head injury. Compared to individuals without head injury, individuals with head injury had worse physical functioning (SPPB total score, ß-coefficient = -0.22, 95% CI: -0.35 to -0.09) and were more likely to be pre-frail (OR = 1.19, 95% CI: 1.04 to 1.35) or frail (OR = 1.40, 95% CI: 1.08 to 1.80) compared to robust. Prospectively, head injury was associated with a 0.02 m/s greater decline (95% CI: -0.04 to -0.01) in gait speed over a median of 5 years. Among baseline robust individuals (n = 1 847), head injury was associated with increased odds of becoming pre-frail (OR = 1.32, 95% CI: 1.04 to 1.67) or frail (OR = 1.92, 95% CI: 1.05 to 3.51) compared to robust. CONCLUSIONS: Older adults with prior head injury had worse physical functioning and greater frailty at baseline and were more likely to become frail and walk slower over time, compared to individuals without head injury.

Association of Win-Loss Record With Neuropsychiatric Symptoms and Brain Health Among Professional Fighters.

OBJECTIVE: Repetitive head impacts in professional fighting commonly lead to head injuries. Increased exposure to repetitive head trauma, measured by the number of professional fights and years of fighting, has been associated with slower processing speed and smaller brain volumes. The impact of win-loss outcomes has been investigated in other sports, with several studies suggesting that individuals on losing teams experience more head injuries. Here, the authors hypothesized that fighters with a worse fight record would exhibit poorer brain health outcomes. METHODS: The Professional Fighters Brain Health Study examined changes in neuropsychiatric symptoms, regional brain volume, and cognition among professional boxers and mixed martial arts fighters. These data were used to evaluate the relationship between win-loss ratios and brain health outcomes among professional fighters (N=212) by using validated neuropsychiatric symptom and cognitive measures and MRI data. RESULTS: Retired fighters with a better record demonstrated more impulsiveness (B=0.21, df=48) and slower processing speed (B=-0.42, df=31). More successful fighters did not perform better than fighters with worse records on any neuropsychiatric or cognitive test. Retired fighters with better fight records had smaller brain volumes in the subcortical gray matter, anterior corpus callosum, left and right hippocampi, left and right amygdala, and left thalamus. More successful active fighters had a smaller left amygdala volume. CONCLUSIONS: These findings suggest that among retired fighters, a better fight record was associated with greater impulsiveness, slower processing speed, and smaller brain volume in certain regions. This study shows that even successful fighters experience adverse effects on brain health.

Timing of Cognitive Test Score Decline Prior to Incident Dementia Diagnosis in Blacks and Whites: The Atherosclerosis Risk in Communities Neurocognitive Study.

INTRODUCTION: Commonly occurring dementias include those of Alzheimer's, vascular, and mixtures of these and other pathologies. They are believed to evolve over many years, but that time interval has been difficult to establish. Our objective was to determine how many years in advance of a dementia diagnosis cognitive scores begin to change. METHODS: 14,086 dementia-free ARIC participants underwent a cognitive exam at baseline visit 2 (1990-1992, mean age 57 ± 5.72), and 11,244 at visit 4 (1996-1998), 5,640 at visit 5 (2011-2013), and 3,574 at visit 6 (2016-2017) with surveillance for dementias of all-causes combined. Within 5-year intervals after each visit, we compared performance on the Delayed Word Recall Test (DWRT), the Digit Symbol Substitution Test (DSST), the Word Fluency Test (WFT), and the combined mean of three cognitive tests at baseline in participants who were diagnosed with dementia within each interval versus those who survived the interval without a dementia diagnosis. Z-scores were adjusted for demographics and education in separate regression models for each visit. We plotted adjusted z-score means by time interval following each visit. RESULTS: During follow-up 3,334, 2,821, 1,218, and 329 dementia cases were ascertained after visits 2, 4, 5, and 6, respectively. Adjusted DWRT z-scores were significantly lower 20-25 years before dementia than those who did not experience dementia within 25 years. DSST z-scores were significantly lower at 25-30 years and 3-test combination z-scores were significantly lower as early as 30-31 years before onset. The difference between dementia and non-dementia group in the visit 2 3-test combination z-score was -0.20 at 30-31 years prior to dementia diagnosis. As expected, differences between the dementia and non-dementia groups increased closer to the time of dementia occurrence, up to their widest point at 0-5 years prior to dementia diagnosis. The difference between dementia and non-dementia groups in the visit 2 3-test combination z-score at 0-5 years was -0.90. WFT z-score differences were smaller than for the DSST or DWRT and began later. Patterns were similar in Black and White participants. CONCLUSION: DWRT, DSST, and combined 3-test z-scores were significantly lower more than 20 years prior to diagnosis in the dementia group versus the non-dementia group. Findings contribute to our knowledge of the long prodromal period in Blacks and Whites.

Trends in Traumatic Brain Injury Mortality in the US.

This cohort study characterizes US trends in traumatic brain injury­related mortality by age, sex, and race and ethnicity.

Associations of Prior Head Injury With Mild Behavioral Impairment Domains.

OBJECTIVE: This study investigated associations of prior head injury and number of prior head injuries with mild behavioral impairment (MBI) domains. SETTING: The Atherosclerosis Risk in Communities (ARIC) Study. PARTICIPANTS: A total of 2534 community-dwelling older adults who took part in the ARIC Neurocognitive Study stage 2 examination were included. DESIGN: This was a prospective cohort study. Head injury was defined using self-reported and International Classification of Diseases, Ninth Revision ( ICD -9) code data. MBI domains were defined using the Neuropsychiatric Inventory Questionnaire (NPI-Q) via an established algorithm mapping noncognitive neuropsychiatric symptoms to the 6 domains of decreased motivation, affective dysregulation, impulse dyscontrol, social inappropriateness, and abnormal perception/thought content. MAIN MEASURES: The primary outcome was the presence of impairment in MBI domains. RESULTS: Participants were a mean age of 76 years, with a median time from first head injury to NPI-Q administration of 32 years. The age-adjusted prevalence of symptoms in any 1+ MBI domains was significantly higher among individuals with versus without prior head injury (31.3% vs 26.0%, P = .027). In adjusted models, a history of 2+ head injuries, but not 1 prior head injury, was associated with increased odds of impairment in affective dysregulation and impulse dyscontrol domains, compared with no history of head injury (odds ratio [OR] = 1.83, 95% CI = 1.13-2.98, and OR = 1.74, 95% CI = 1.08-2.78, respectively). Prior head injury was not associated with symptoms in MBI domains of decreased motivation, social inappropriateness, and abnormal perception/thought content (all P > .05). CONCLUSION: Prior head injury in older adults was associated with greater MBI domain symptoms, specifically affective dysregulation and impulse dyscontrol. Our results suggest that the construct of MBI can be used to systematically examine the noncognitive neuropsychiatric sequelae of head injury; further studies are needed to examine whether the systematic identification and rapid treatment of neuropsychiatric symptoms after head injury is associated with improved outcomes.

Association between structural brain MRI abnormalities and epilepsy in older adults.

OBJECTIVE: To determine the association between brain MRI abnormalities and incident epilepsy in older adults. METHODS: Men and women (ages 45-64 years) from the Atherosclerosis Risk in Communities study were followed up from 1987 to 2018 with brain MRI performed between 2011 and 2013. We identified cases of incident late-onset epilepsy (LOE) with onset of seizures occurring after the acquisition of brain MRI. We evaluated the relative pattern of cortical thickness, subcortical volume, and white matter integrity among participants with incident LOE after MRI in comparison with participants without seizures. We examined the association between MRI abnormalities and incident LOE using Cox proportional hazards regression. Models were adjusted for demographics, hypertension, diabetes, smoking, stroke, and dementia status. RESULTS: Among 1251 participants with brain MRI data, 27 (2.2%) developed LOE after MRI over a median of 6.4 years (25-75 percentile 5.8-6.9) of follow-up. Participants with incident LOE after MRI had higher levels of cortical thinning and white matter microstructural abnormalities before seizure onset compared to those without seizures. In longitudinal analyses, greater number of abnormalities was associated with incident LOE after controlling for demographic factors, risk factors for cardiovascular disease, stroke, and dementia (gray matter: hazard ratio [HR]: 2.3, 95% confidence interval [CI]: 1.0-4.9; white matter diffusivity: HR: 3.0, 95% CI: 1.2-7.3). INTERPRETATION: This study demonstrates considerable gray and white matter pathology among individuals with LOE, which is present prior to the onset of seizures and provides important insights into the role of neurodegeneration, both of gray and white matter, and the risk of LOE.

Normative Data for the 12-Item Sniffin' Sticks Odor Identification Test in Older Adults.

OBJECTIVE: Quantitative olfactory assessment has demonstrated clinical utility for the evaluation of a range of neurologic, psychiatric, and sinonasal conditions. Here, we provide age, sex, race, and education-specific normative data for the 12-item Sniffin Sticks Odor Identification Test (SSOIT-12) in older Black and White U.S. adults without preclinical or clinical dementia or sinonasal disease. METHOD: A sample of 2,224 Atherosclerosis Risk in Communities study participants aged 66-89 years were included. A normative regression equation was developed using a linear model for the association of age, sex, race, and education with odor identification score. Regression-based normative mean scores and percentiles were generated by age, sex, race, and education groups. RESULTS: Participants (mean age = 74 years, 59% women, 20% Black, 48% > high school education) had a mean SSOIT-12 score of 9.8. Age, sex, race, and education were all associated with odor identification performance (all ps < .05). A linear regression model for the predicted SSOIT-12 score was developed for use with an individual's actual SSOIT-12 score in order to calculate the Z-score and corresponding percentile for a specific age, sex, race, and education group. Data are also reported in tabular format. CONCLUSIONS: Our study provides SSOIT-12 normative data obtained from a large population of White and Black older adults without preclinical or clinical dementia or sinonasal disease living in the USA. These findings can aid clinicians in assessing the degree of olfactory loss, establishing concordance with a person's perception of olfactory difficulties and quantitatively monitoring changes in olfactory performance over time.