Demographic and Clinical Characteristics Associated With Serum GFAP Levels in an Ethnically Diverse Cohort.

BACKGROUND AND OBJECTIVES: Elevations in circulating glial fibrillary acidic protein (GFAP), a putative marker of reactive astrocytosis, have been found to associate with cognitive decline and dementia status. Further validation in diverse cohorts and evaluation of potential health disparities are necessary for broader generalization. The goal of this study was to examine the associations between demographics, cardiovascular risk factors, and APOE ε4 status with serum GFAP levels among Mexican American and non-Hispanic White older adults across the continuum from cognitively unimpaired to Alzheimer disease dementia. METHODS: Serum GFAP levels were assayed using a Simoa HD-1 analyzer in older adults enrolled in the observational Texas Alzheimer Research and Care Consortium. Associations between demographic and clinical characteristics with serum GFAP levels were evaluated using linear regression. The diagnostic accuracy of serum GFAP was further examined using area under the receiver operating characteristic curves (AUROC) in univariate and adjusted models, and optimal cut points were derived using the maximum Kolmogorov-Smirnov metric. All models were also stratified by ethnicity and disease stage. RESULTS: A total of 1,156 Mexican American and 587 non-Hispanic White participants were included (mean age = 68 years, standard deviation = 10; 65% female). Older age (ß = 0.562 (95% CI 0.515-0.609), p < 0.001), apolipoprotein ε4 status (ß = 0.139 (95% CI 0.092-0.186), p < 0.001), and cognitive impairment (ß = 0.150 (95% CI 0.103-0.197), p < 0.001) were positively associated with serum GFAP. By contrast, higher body mass index (ß = -0.181 (95% CI -0.228 to -0.134), p < 0.001), diabetes (ß = -0.065 (95% CI -0.112 to -0.018), p < 0.001), and tobacco use (ß = -0.059 (95% CI -0.106 to -0.012), p < 0.001) were inversely associated with serum GFAP. AUROC values were generally comparable across ethnicities and model fit improved with inclusion of additional covariates. However, optimal cut-off values were consistently lower in Mexican Americans relative to non-Hispanic White participants. DISCUSSION: The study results highlight the importance of understanding the role of broader demographic and clinical factors on circulating GFAP levels within diverse cohorts to enhance precision across clinical, research, and community settings.

End-of-Life Experiences Within a Dementia Support Program During COVID-19: Context and Circumstances Surrounding Death During the Pandemic.

Background: Persons with dementia (PWD) and their caregivers are uniquely impacted by the COVID-19 pandemic, including higher risk of mortality for PWD. Objectives: To describe the context and circumstances of deaths of PWD within a dementia support program during the COVID-19 pandemic. Design: Retrospective data collection of PWD deaths between March 1, 2020 and February 28, 2021. Setting/Subjects: Decedents enrolled in Care Ecosystem, a multidisciplinary team model for dementia care at University of California San Francisco, Ochsner Health, and UCHealth. Measurements: Using mixed methods, we analyzed data using descriptive measures and team-based thematic analysis to understand the end-of-life (EOL) experience of PWD-caregiver dyads. Results: Twenty-nine PWD died across three sites. Almost half (45%) were between ages 70-79 and 12 (41%) were women. Eighteen (62%) died at a private residence; two died in the hospital. Hospice was involved for 22 (76%) patients. There were known causes of death for 15 (53%) patients. Only two deaths were directly related to COVID-19 infection. Social isolation was perceived to have a high or very high impact for 12 (41%) decedents. Four qualitative themes were identified: (1) isolation due to the pandemic, (2) changes in use of dementia supports and resources, (3) impact on goals of care decisions, and (4) communication challenges for EOL care coordination. Conclusion: Among PWD and caregivers enrolled in a dementia support program, the COVID-19 pandemic had direct and indirect influences on mortality and EOL experiences of PWD. Caregivers' experiences of caring, decision making, and bereavement were also affected.

Evaluating racial disparities in healthcare system utilization and caregiver burden among older adults with dementia.

OBJECTIVE: To evaluate racial differences in healthcare utilization and caregiver burden in a culturally diverse population of older adults with dementia. METHOD: One hundred and thirty-three dyads (person with dementia, PWD and caregiver, CG), with at least one emergency department (ED) visit or hospitalization 12 months prior, were enrolled. Independent sample t-tests and chi-squared analyses were performed to compare racial groups on healthcare utilization and CG burden. Mann-Whitney U test was used for item-level analyses, principal component analysis was used to examine relationships among outcomes, and regressions were used to identify the relationship between race and potential covariates. RESULTS: PWD sample mean age was 79 years, predominantly female, and with high school education. Racial distribution was 65% White and 35% Black. CG sample mean age was 64 years, predominantly female, with more than 12 years of education. No differences were found for age or dementia severity across racial groups. Black PWD experienced more ED and ambulance utilization when compared to White counterparts. Non-emergency hospitalization rates were higher for White PWD. No significant differences were found by race for CG burden total score; however, item-level analysis suggested more anger, reduced social life, uncertainty, and inadequacy in White CGs. Regressions demonstrated a positive relationship between Black race and adult-child CGs with increased ED visits, while dyad educational attainment was associated with hospitalizations independent of race. CONCLUSIONS: Healthcare utilization disparities extend to older adults with dementia diagnoses. Our findings suggest that culturally tailored interventions may be appropriate. Future research is encouraged to explore the effect of other covariates.

Acceptability and Feasibility of a Multicomponent Telehealth Care Management Program in Older Adults With Advanced Dementia in a Residential Memory Care Unit.

The aim of the current study was to examine the acceptability and feasibility of a multicomponent care management program in older adults with advanced dementia in a long-term memory care unit. Eighteen older adults with moderate to severe dementia were asked to wear an activity monitor (Fitbit Charge 2 HR) and participate in a once monthly telehealth intervention via iPads over a 6-month period. Activity monitor data were used to assess compliance. Acceptability was assessed through qualitative interviews conducted with the caregiving staff on the memory unit. The care management program was acceptable to residents and their caregivers. Results indicated that the care management program is feasible in older adults with advanced dementia although activity monitor adherence was better during the day than at night. Telehealth session compliance was excellent throughout the study. A long-term multicomponent dementia care program is acceptable and feasible in individuals with advanced dementia. Future studies should aim to evaluate whether data received from activity monitors can be used in a dementia care intervention program.

Baseline Performance and Psychometric Properties of the Child Sport Concussion Assessment Tool 3 (Child-SCAT3) in 5- to 13-year-old Athletes.

OBJECTIVE: To determine the normative, baseline performance and psychometric properties of the Child Sport Concussion Assessment Tool 3 (Child-SCAT3) in 5- to 13-year-old athletes. DESIGN: Cross-sectional study. SETTING: Practice fields. PARTICIPANTS: Contact sport athletes (N = 155) 5 to 13 years old. INDEPENDENT VARIABLES: Age, gender, verbal intellectual functioning (receptive vocabulary). MAIN OUTCOME MEASURES: Child-SCAT3: self-reported and parent-reported symptoms, cognitive performance (child form of the Standardized Assessment of Concussion; SAC-C), and balance (modified Balance Error Scoring System, mBESS-C; tandem gait). A subset of the sample repeated the Child-SCAT3 at another date. Some subjects also completed the Adult-SCAT3 version of the symptom checklist and mBESS. RESULTS: Small-to-medium-sized effects of age were observed on all Child-SCAT3 components. Effects of gender and receptive vocabulary were observed on select components of the SCAT3. Younger age and lower receptive vocabulary were independently associated with greater symptom endorsement, yet parents rated higher symptom burden for older children. Internal consistency reliability and stability of symptom ratings was good to excellent. Stability was more modest for SAC-C and tandem gait scores and very poor for mBESS-C scores, perhaps due to restricted variance. Inter-rater reliability (self-rated vs parent-rated symptoms) was fair. CONCLUSIONS: The Child-SCAT3 self-report symptom checklist may be inappropriate to administer to younger school-aged children. Some of the age effects observed warrant use of demographically appropriate norms in Child-SCAT3 interpretation. The findings can provide guidance for clinicians assessing children of varying ages and point to directions for further development of refined approaches for pediatric concussion assessment.

Preinjury somatization symptoms contribute to clinical recovery after sport-related concussion.

OBJECTIVE: To determine the degree to which preinjury and acute postinjury psychosocial and injury-related variables predict symptom duration following sport-related concussion. METHODS: A total of 2,055 high school and collegiate athletes completed preseason evaluations. Concussed athletes (n = 127) repeated assessments serially (<24 hours and days 8, 15, and 45) postinjury. Cox proportional hazard modeling was used to predict concussive symptom duration (in days). Predictors considered included demographic and history variables; baseline psychological, neurocognitive, and balance functioning; acute injury characteristics; and postinjury clinical measures. RESULTS: Preinjury somatic symptom score (Brief Symptom Inventory-18 somatization scale) was the strongest premorbid predictor of symptom duration. Acute (24-hour) postconcussive symptom burden (Sport Concussion Assessment Tool-3 symptom severity) was the best injury-related predictor of recovery. These 2 predictors were moderately correlated (r = 0.51). Path analyses indicated that the relationship between preinjury somatization symptoms and symptom recovery was mediated by postinjury concussive symptoms. CONCLUSIONS: Preinjury somatization symptoms contribute to reported postconcussive symptom recovery via their influence on acute postconcussive symptoms. The findings highlight the relevance of premorbid psychological factors in postconcussive recovery, even in a healthy athlete sample relatively free of psychopathology or medical comorbidities. Future research should elucidate the neurobiopsychosocial mechanisms that explain the role of this individual difference variable in outcome following concussive injury.

Acute white matter changes following sport-related concussion: A serial diffusion tensor and diffusion kurtosis tensor imaging study.

Recent neuroimaging studies have suggested that following sport-related concussion (SRC) physiological brain alterations may persist after an athlete has shown full symptom recovery. Diffusion MRI is a versatile technique to study white matter injury following SRC, yet serial follow-up studies in the very acute stages following SRC utilizing a comprehensive set of diffusion metrics are lacking. The aim of the current study was to characterize white matter changes within 24 hours of concussion in a group of high school and collegiate athletes, using Diffusion Tensor and Diffusion Kurtosis Tensor metrics. Participants were reassessed a week later. At 24 hours post-injury, the concussed group reported significantly more concussion symptoms than a well-matched control group and demonstrated poorer performance on a cognitive screening measure, yet these differences were nonsignificant at the 8-day follow-up. Similarly, within 24-hours after injury, the concussed group exhibited a widespread decrease in mean diffusivity, increased axial kurtosis and, to a lesser extent, decreased axial and radial diffusivities compared with control subjects. At 8 days post injury, the differences in these diffusion metrics were even more widespread in the injured athletes, despite improvement of symptoms and cognitive performance. These MRI findings suggest that the athletes might not have reached full physiological recovery a week after the injury. These findings have significant implications for the management of SRC because allowing an athlete to return to play before the brain has fully recovered from injury may have negative consequences. Hum Brain Mapp 37:3821-3834, 2016. © 2016 Wiley Periodicals, Inc.

Sport-Related Concussion Reporting and State Legislative Effects.

OBJECTIVE: To investigate concussion rates and reporting frequencies in high school and collegiate athletes in 2013, compare results to those obtained from 1999 to 2002, and examine to what extent the 2012 Wisconsin state concussion law affected reporting in 2013. DESIGN: Retrospective 2013 survey compared with prior survey. SETTING: High schools and colleges in the Milwaukee, Wisconsin, area. PARTICIPANTS: Athletes (N = 784) from multiple sports were surveyed in 2013. Football players (N = 1532) from 1999 to 2002 completed the same measure. MAIN OUTCOME MEASURES: Both surveys assessed concussion history, concussion incidence during the current season, whether incident concussions were reported, who concussions were reported to, and reasons for not reporting. The 2013 survey also assessed awareness of the Wisconsin state law and its effect on reporting. RESULTS: Rates of concussion in the surveyed season were comparable to previous findings from 1999 to 2002 (16.6% vs 15.3%, P = 0.558). Notably, athletes were significantly more likely to report their concussions in 2013 (70.6% vs 47.3% previously, P = 0.011). Among high school athletes surveyed, 59.5% were aware of the Wisconsin state law, with 55.1% stating it would make them more likely to report a concussion. CONCLUSIONS: Rates of concussion for 1 sport season have not changed significantly over the past 14 years. The percentage of concussions that are reported to someone has increased significantly. Awareness of the Wisconsin state law does not fully account for the increase in concussion reporting. CLINICAL RELEVANCE: Given the finite amount of knowledge regarding the influence of concussion-related cultural and legal changes, these findings will help to inform clinicians of the current concussion milieu from the perspective of athletes. It will inform practitioners involved in concussion management to what extent athletes are aware of and report concussions.

Cerebral Blood Flow Alterations in Acute Sport-Related Concussion.

Sport-related concussion (SRC) is a major health problem, affecting millions of athletes each year. While the clinical effects of SRC (e.g., symptoms and functional impairments) typically resolve within several days, increasing evidence suggests persistent neurophysiological abnormalities beyond the point of clinical recovery after injury. This study aimed to evaluate cerebral blood flow (CBF) changes in acute SRC, as measured using advanced arterial spin labeling (ASL) magnetic resonance imaging (MRI). We compared CBF maps assessed in 18 concussed football players (age, 17.8 ± 1.5 years) obtained within 24 h and at 8 days after injury with a control group of 19 matched non-concussed football players. While the control group did not show any changes in CBF between the two time-points, concussed athletes demonstrated a significant decrease in CBF at 8 days relative to within 24 h. Scores on the clinical symptom (Sport Concussion Assessment Tool 3, SCAT3) and cognitive measures (Standardized Assessment of Concussion [SAC]) demonstrated significant impairment (vs. pre-season baseline levels) at 24 h (SCAT, p < 0.0001; SAC, p < 0.01) but returned to baseline levels at 8 days. Two additional computerized neurocognitive tests, the Automated Neuropsychological Assessment Metrics and Immediate Post-Concussion and Cognitive Testing, showed a similar pattern of changes. These data support the hypothesis that physiological changes persist beyond the point of clinical recovery after SRC. Our results also indicate that advanced ASL MRI methods might be useful for detecting and tracking the longitudinal course of underlying neurophysiological recovery from concussion.

Prospective, Head-to-Head Study of Three Computerized Neurocognitive Assessment Tools (CNTs): Reliability and Validity for the Assessment of Sport-Related Concussion.

Limited data exist comparing the performance of computerized neurocognitive tests (CNTs) for assessing sport-related concussion. We evaluated the reliability and validity of three CNTs-ANAM, Axon Sports/Cogstate Sport, and ImPACT-in a common sample. High school and collegiate athletes completed two CNTs each at baseline. Concussed (n=165) and matched non-injured control (n=166) subjects repeated testing within 24 hr and at 8, 15, and 45 days post-injury. Roughly a quarter of each CNT's indices had stability coefficients (M=198 day interval) over .70. Group differences in performance were mostly moderate to large at 24 hr and small by day 8. The sensitivity of reliable change indices (RCIs) was best at 24 hr (67.8%, 60.3%, and 47.6% with one or more significant RCIs for ImPACT, Axon, and ANAM, respectively) but diminished to near the false positive rates thereafter. Across time, the CNTs' sensitivities were highest in those athletes who became asymptomatic within 1 day before neurocognitive testing but was similar to the tests' false positive rates when including athletes who became asymptomatic several days earlier. Test-retest reliability was similar among these three CNTs and below optimal standards for clinical use on many subtests. Analyses of group effect sizes, discrimination, and sensitivity and specificity suggested that the CNTs may add incrementally (beyond symptom scores) to the identification of clinical impairment within 24 hr of injury or within a short time period after symptom resolution but do not add significant value over symptom assessment later. The rapid clinical recovery course from concussion and modest stability probably jointly contribute to limited signal detection capabilities of neurocognitive tests outside a brief post-injury window. (JINS, 2016, 22, 24-37).