Robust language-based mental health assessments in time and space through social media.

In the most comprehensive population surveys, mental health is only broadly captured through questionnaires asking about "mentally unhealthy days" or feelings of "sadness." Further, population mental health estimates are predominantly consolidated to yearly estimates at the state level, which is considerably coarser than the best estimates of physical health. Through the large-scale analysis of social media, robust estimation of population mental health is feasible at finer resolutions. In this study, we created a pipeline that used ~1 billion Tweets from 2 million geo-located users to estimate mental health levels and changes for depression and anxiety, the two leading mental health conditions. Language-based mental health assessments (LBMHAs) had substantially higher levels of reliability across space and time than available survey measures. This work presents reliable assessments of depression and anxiety down to the county-weeks level. Where surveys were available, we found moderate to strong associations between the LBMHAs and survey scores for multiple levels of granularity, from the national level down to weekly county measurements (fixed effects ß = 0.34 to 1.82; p < 0.001). LBMHAs demonstrated temporal validity, showing clear absolute increases after a list of major societal events (+23% absolute change for depression assessments). LBMHAs showed improved external validity, evidenced by stronger correlations with measures of health and socioeconomic status than population surveys. This study shows that the careful aggregation of social media data yields spatiotemporal estimates of population mental health that exceed the granularity achievable by existing population surveys, and does so with generally greater reliability and validity.

Genome-wide association analyses identify 95 risk loci and provide insights into the neurobiology of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Cognitive Decline After Divorce and Widowhood: Is Marital Loss Always a Loss?

Background and Objectives: We used longitudinal data to determine whether the type of marital loss is associated with the rate of cognitive change before and after divorce or widowhood. Previous research found that relationship status was associated with older adults' cognitive performance: married persons performed better on memory assessments and had lower dementia risk than unmarried-cohabitating, never-married, divorced, and widowed persons. However, the end of a marriage may cause distress or reduce distress because a stressor disappears. Questions thus remain about the mechanisms by which marital change affects cognitive outcomes and, specifically, whether termination of marriage can improve cognitive performance for some. Research Design and Methods: Using data from the 1998-2016 waves of the Health and Retirement Study (N = 23,393), we conducted two analyses. First, we used trajectory analysis to create clusters of participants with similar cognitive trajectories and tested the association between participants' cluster membership and marital loss type. Second, we used multilevel modeling to analyze the relationship between participants' cognitive scores while married and following divorce or widowhood and linked these to marital features. Results: Participants who divorced showed no difference in trajectory distribution; widowed participants were more likely to be in the lower-performing and more quickly declining groups. Participants had lower rates of decline following divorce (ß = .136, p < .001), while widowed participants had accelerated decline following spousal death (ß = -0.183, p < .001) and an immediate decline following spousal death (ß = -0.113, p = .028). Discussion and Implications: We found that the type of marital loss was important, and predicted improvements in cognition for some and decrements for others, with individuals who were divorced performing best while those who were widowed or separated but not divorced performing worse.

Optimization of [18F]-FDOPA Brain PET Acquisition Times for Assessment of Parkinsonism in the Clinical Setting.

BACKGROUND AND PURPOSE: Fluorine 18-fluoro-L-dopa ([18F]-FDOPA) was approved by the FDA in 2019 and reimbursed by the Centers for Medicare & Medicaid Services in 2022 for use with PET to visualize dopaminergic nerve terminals in the striatum for evaluation of parkinsonism. We sought to determine the optimal image acquisition time for [18F]-FDOPA PET by evaluating rater-estimated FDOPA positivity and image quality across 4 time points. MATERIALS AND METHODS: Brain PET/CT was acquired 90 minutes following injection of 185 megabecquerel (5 mCi) of [18F]-FDOPA. PET was acquired in list mode for 20 minutes, and data were replayed to represent 15-, 10-, and 5-minute acquisitions. By means of MIMneuro, PET/MR imaging or PET/CT was independently graded for FDOPA positivity and image quality by 2 readers, blinded to the clinical report and diagnosis. Expert neuroradiologist clinical reads were used as the criterion standard. RESULTS: Twenty patients were included, average age 65.6 years, 55% women. Image-quality ratings decreased with shorter acquisition times for both readers (reader 1, ρ = 0.23, P = .044; reader 2, ρ = 0.24, P = .036), but there was no association between abnormality confidence scores and acquisition time (reader 1, ρ = -0.13, P = .250; reader 2, ρ = -0.19, P = .100). There was a high degree of consistency in intra- and interrater agreement and agreement with the expert reads when using acquisition times of ≥10 minutes (maximal confidence score consistency [ρ = 0.92] and interrater agreement [κ = 0.90] were observed at 15 minutes), while image quality was consistently rated as low and FDOPA positivity ratings were inconsistent when using a 5-minute acquisition time. CONCLUSIONS: Our study suggests that image-quality ratings were stable after 15 minutes and that between-subject abnormality detection rates were highly consistent between the 2 readers when acquired for at least 10 and up to 20 minutes but were inconsistent at 5 minutes. Shorter [18F]-FDOPA PET acquisition times may help maximize patient comfort while increasing throughput in the clinical setting.

A novel approach to model cumulative stress: Area under the s-factor curve.

OBJECTIVE: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to model the accumulation of stressors, and to determine whether the rate of change in stressors or traditional composite scores of stressors are stronger predictors of health outcomes. METHOD: We used factor analysis to estimate a stress-factor score and then, to operationalize the accumulation of stressors we examined five approaches to aggregating information about repeated exposures to multiple stressors. The predictive validity of these approaches was then assessed in relation to different health outcomes. RESULTS: The prediction of chronic conditions, body mass index, difficulty with activities of daily living, executive function, and episodic memory later in life was strongest when the accumulation of stressors was modeled using total area under the curve (AUC) of estimated factor scores, compared to composite scores that have traditionally been used in studies of cumulative stress, as well as linear rates of change. CONCLUSIONS: Like endogenous, biological markers of stress reactivity, AUC for individual trajectories of self-reported stressors shows promise as a data reduction technique to model the accumulation of stressors in longitudinal studies. Overall, our results indicate that considering different quantitative models is critical to understanding the sequelae and predictive power of psychosocial stressors from midlife to late adulthood.

Mediterranean diet intervention among World Trade Center responders with post-traumatic stress disorder: Feasibility and outcomes of a pilot randomized controlled trial.

Objective: Responders of the World Trade Center (WTC) disaster suffer from co-morbidities. A Mediterranean Diet (MedDiet) nutrition intervention with physical activity was implemented among WTC responders with overweight/obesity and post-traumatic stress disorder (PTSD). Methods: WTC Health Program members (N = 62), 45-65 years, males 87%, body mass index (BMI) 27-45 kg/m2 randomized to MedDiet (n = 31) or usual nutrition counseling (n = 31). The 10-week intervention included online nutrition education, text messages, and group experiential cooking; both groups had three in-person individual nutrition counseling. Anthropometrics, serum biomarkers, psychosocial factors, MedDiet score, and PTSD symptoms were assessed at baseline, post-intervention, and 3-months (follow-up). The primary outcome was intervention feasibility and secondary outcomes were within- and between-group changes of all measures at post-intervention and follow-up. Nonparametric Wilcoxon rank sum tests for between-group comparisons and Wilcoxon signed rank tests for pre-post within-group comparisons. Results: A total of 58(94%) and 46(74%) participants completed the post-intervention and follow-up measurements, respectively. Both groups experienced significant improvements in anthropometrics, MedDiet score, oxidized low-density lipoprotein, and PTSD symptoms. Baseline median (range) were weight 100.42 (73.66-135.17) kg, BMI 33.20 (27.50-41.75) kg/m2, and Waist circumference (WC) 109.22 (90.17-150.62) cm. Median % weight loss at post-intervention was MedDiet: -3% (-11%-7%), p = 0.0002; Control: -1% (-13%-4%), p = 0.008 and at follow-up MedDiet: -2% (-14%-12%), p = 0.07; Control: -2% (-20%-3%), p = 0.006. The overall BMI was reduced by -0.68 kg/m2 (-4.61-2.09) kg/m2 p < 0.0001 at post-intervention and by -0.60 kg/m2 (-6.91-3.39) kg/m2, p < 0.0009 at follow-up. Overall, median WC was reduced (p < 0.0001); post-intervention -3.81 cm (-33.00-3.30)cm and follow-up -4.45(-38.10-4.57)cm. There were group differences in HbA1c (p = 0.019) and serum ω6/ω3 (p = 0.029) at post-intervention. Conclusion: Online intervention with personal counseling was feasible in this population. Improvements in anthropometrics, MedDiet score, selected serum biomarkers and PTSD symptoms were found in both groups; group differences in HbA1c and serum ω6/ω3. A larger study with a delayed control is needed to better assess intervention effects.

Quantifying Healthy Aging in Older Veterans Using Computational Audio Analysis.

BACKGROUND: Researchers are increasingly interested in better methods for assessing the pace of aging in older adults, including vocal analysis. The present study sought to determine whether paralinguistic vocal attributes improve estimates of the age and risk of mortality in older adults. METHODS: To measure vocal age, we curated interviews provided by male U.S. World War II Veterans in the Library of Congress collection. We used diarization to identify speakers and measure vocal features and matched recording data to mortality information. Veterans (N = 2 447) were randomly split into testing (n = 1 467) and validation (n = 980) subsets to generate estimations of vocal age and years of life remaining. Results were replicated to examine out-of-sample utility using Korean War Veterans (N = 352). RESULTS: World War II Veterans' average age was 86.08 at the time of recording and 91.28 at the time of death. Overall, 7.4% were prisoners of war, 43.3% were Army Veterans, and 29.3% were drafted. Vocal age estimates (mean absolute error = 3.255) were within 5 years of chronological age, 78.5% of the time. With chronological age held constant, older vocal age estimation was correlated with shorter life expectancy (aHR = 1.10; 95% confidence interval: 1.06-1.15; p < .001), even when adjusting for age at vocal assessment. CONCLUSIONS: Computational analyses reduced estimation error by 71.94% (approximately 8 years) and produced vocal age estimates that were correlated with both age and predicted time until death when age was held constant. Paralinguistic analyses augment other assessments for individuals when oral patient histories are recorded.

Behavioral Impairments and Increased Risk of Cortical Atrophy Risk Scores Among World Trade Center Responders.

Objective: World Trade Center (WTC) responders are susceptible to both cognitive and neuropsychiatric impairments, particularly chronic posttraumatic stress disorder. The present study examined self-reported behavioral impairments in a sample of 732 WTC responders, 199 of whom were determined to have high risk of WTC-related cortical atrophy by an artificial neural network. Results: We found that responders at increased risk of cortical atrophy showed behavioral impairment across five domains: motivation, mood, disinhibition, empathy, and psychosis (14.6% vs 3.9% in the low-risk group; P = 3.90 × 10-7). Factor analysis models revealed that responders at high risk of cortical atrophy tended to have deficits generalized across all aspects of behavioral impairment with focal dysfunction in sensory psychosis. We additionally describe how relationships are modulated by exposure severity and pharmacological treatments. Discussion: Our findings suggest a potential link between sensory deficits and the development of cortical atrophy in WTC responders and may indicate symptoms consistent with a clinical portrait of parietal dominant Alzheimer's disease or a related dementia (ADRD). Results underscore the importance of investigating neuropsychiatric symptomatology in clinical evaluations of possible ADRD.

ASSESSMENT AND CHARACTERIZATION OF COVID-19 RELATED COGNITIVE DECLINE: RESULTS FROM A NATURAL EXPERIMENT.

Background: Cognitive impairment is the most common and disabling manifestation of post-acute sequelae of SARS-CoV-2. There is an urgent need for the application of more stringent methods for evaluating cognitive outcomes in research studies. Objective: To determine whether cognitive decline emerges with the onset of COVID-19 and whether it is more pronounced in patients with Post-Acute Sequelae of SARS-CoV-2 or severe COVID-19. Methods: This longitudinal cohort study compared the cognitive performance of 276 patients with COVID-19 to that of 217 controls across four neuroinflammation or vascular disease-sensitive domains of cognition using data collected both before and after the pandemic starting in 2015. Results: The mean age of the COVID-19 group was 56.04±6.6 years, while that of the control group was 58.1±7.3 years. Longitudinal models indicated a significant decline in cognitive throughput ((ß=-0.168, P=.001) following COVID-19, after adjustment for pre-COVID-19 functioning, demographics, and medical factors. The effect sizes were large; the observed changes in throughput were equivalent to 10.6 years of normal aging and a 59.8% increase in the burden of mild cognitive impairment. Cognitive decline worsened with coronavirus disease 2019 severity and was concentrated in participants reporting post-acute sequelae of SARS-CoV-2. Conclusion: COVID-19 was most likely associated with the observed cognitive decline, which was worse among patients with PASC or severe COVID-19. Monitoring patients with post-acute sequelae of SARS-CoV-2 for declines in the domains of processing speed and visual working memory and determining the long-term prognosis of this decline are therefore warranted.

Racial/Ethnic Disparities in Prostate Cancer 5-Year Survival: The Role of Health-Care Access and Disease Severity.

INTRODUCTION: Prostate cancer (PCa) exhibits one of the widest racial and socioeconomic disparities. PCa disparities have also been widely linked to location, as living in more deprived regions was associated with lower healthcare access and worse outcomes. This study aims to examine PCa survival across various USA counties in function of different socioeconomic profiles and discuss the role of potential intermediary factors. METHODS: The SEER database linked to county-level SES was utilized. Five-year PCa-specific survival using the Kaplan-Meier method was performed for five racial/ethnic categories in function of SES quintiles. Multilevel Cox proportional hazards regression was performed to assess the relationship between county-level SES and PCa survival. Multivariate regression analysis was performed to examine the role of healthcare utilization and severity. RESULTS: A total of 239,613 PCa records were extracted, and 5-year PCa-specific survival was 94%. Overall, living in counties in the worst poverty/income quintile and the worst high-school level education increased PCa mortality by 38% and 33%, respectively, while the best bachelor's-level education rates decreased mortality risk by 23%. Associations varied considerably upon racial/ethnic stratification. Multilevel analyses showed varying contributions of individual and area-level factors to survival within minorities. The relationship between SES and PCa survival appeared to be influenced by healthcare utilization and disease stage/grade. DISCUSSION: Racial/ethnic categories responded differently under similar county-level SES and individual-level factors to the point where disparities reversed in Hispanic populations. The inclusion of healthcare utilization and severity factors may provide partial early support for their role as intermediaries. Healthcare access (insurance) might not necessarily be associated with better PCa survival through the performance of biopsy and or/surgery. County-level education plays an important role in PCa decision making as it might elucidate discussions of other non-invasive management options. CONCLUSIONS: The findings of this study demonstrate that interventions need to be tailored according to each group's needs. This potentially informs the focus of public health efforts in terms of planning and prioritization. This study could also direct further research delving into pathways between area-level characteristics with PCa survival.

Discovery of 95 PTSD loci provides insight into genetic architecture and neurobiology of trauma and stress-related disorders.

Posttraumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 novel). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (e.g., GRIA1, GRM8, CACNA1E ), developmental, axon guidance, and transcription factors (e.g., FOXP2, EFNA5, DCC ), synaptic structure and function genes (e.g., PCLO, NCAM1, PDE4B ), and endocrine or immune regulators (e.g., ESR1, TRAF3, TANK ). Additional top genes influence stress, immune, fear, and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Crisis response during the COVID-19 pandemic: Changes in social contact and social participation of older Americans.

OBJECTIVE: This study aimed to assess changes in social contact with family, friends and healthcare providers, as well as social participation in working, volunteering, religious services and other organized activities, among older adults during the COVID-19 pandemic while examining the role of pre-COVID sociodemographic characteristics or cognitive and physical limitations in changes in social contact and participation. METHODS: We conducted secondary data analyses in the National Health and Aging Trends Study (NHATS) COVID-19 questionnaire, collected in 2020 during a period of workplace closures and social distancing guidelines. We linked data to pre-COVID sociodemographic and medical information collected in 2019 before COVID interrupted social life. The frequency of participants' social contact and social participation prior to and during the COVID-19 pandemic, were compared using paired t-tests for summed scores. Multivariate linear regression was used to relate participants' socio-demographic, prior physical and cognitive performance with levels of social contact and participation and with changes reported during the COVID-19 pandemic. RESULTS: In total, results from 2,486 eligible participants revealed that COVID-19 was associated with decreased social contact among family and friends (change: -0.62; SE: 0.06; p<0.0001), and social participation among older adults (change: -0.58; SE: 0.02; p<0.0001). Pre-COVID characteristics including older age, lower educational attainment, poorer physical performance, and more chronic conditions were associated with lower social contact and social participation and with how older adults adapted their social lives during the COVID-19 pandemic. DISCUSSION: These results emphasize the importance of increasing digital inclusion for older adults in a major crisis.

Functional changes in neural mechanisms underlying post-traumatic stress disorder in World Trade Center responders.

World Trade Center (WTC) responders exposed to traumatic and environmental stressors during rescue and recovery efforts have a high prevalence of chronic WTC-related post-traumatic stress disorder (WTC-PTSD). We investigated neural mechanisms underlying WTC-PTSD by applying eigenvector centrality (EC) metrics and data-driven methods on resting state functional magnetic resonance (fMRI). We identified how EC differences relate to WTC-exposure and behavioral symptoms. We found that connectivity differentiated significantly between WTC-PTSD and non-PTSD responders in nine brain regions, as these differences allowed an effective discrimination of PTSD and non-PTSD responders based solely on analysis of resting state data. Further, we found that WTC exposure duration (months on site) moderates the association between PTSD and EC values in two of the nine brain regions; the right anterior parahippocampal gyrus and the left amygdala (p = 0.010; p = 0.005, respectively, adjusted for multiple comparisons). Within WTC-PTSD, a dimensional measure of symptom severity was positively associated with EC values in the right anterior parahippocampal gyrus and brainstem. Functional neuroimaging can provide effective tools to identify neural correlates of diagnostic and dimensional indicators of PTSD.

Social inequalities and the early provision and dispersal of COVID-19 vaccinations in the United States: A population trends study.

BACKGROUND: In December 2020 the U.S. began a massive COVID-19 vaccination campaign, an action that researchers felt could catalyze inequalities in COVID-19 vaccination utilization. While vaccines have the potential to be accessible regardless of social status, the objective of this study was to examine how and when socioeconomic status (SES) and racial/ethnic inequalities would emerge in vaccination distribution. METHODS: Population vaccination rates reported at the county level by the Centers for Disease Control and Prevention across 46 states on 3/30/2021. Correlates included SES, the share of the population who were Black, Hispanic, Female, or aged ≥65 years, and urbanicity (thousands of residents per square mile). Multivariable-adjusted analyses relied on zero-inflated negative binomial regression to estimate the odds of providing any vaccine, and vaccination rate ratios (aVRR) comparing the distribution rate for vaccinations across the U.S. RESULTS: Across the U.S., 16.3 % of adults and 37.9 % of adults aged 65 and older were vaccinated in lower SES counties, while 20.45 % of all adults and 48.15 % of adults aged 65 and older were vaccinated in higher SES counties. Inequalities emerged after 41 days, when < 2 % of Americans were vaccinated. Multivariable-adjusted analyses revealed that higher SES was associated with improved vaccination distribution (aVRR = 1.127, [1.100-1.155], p < 1E-06), while increases in the percent reporting Black or Hispanic race/ethnicity was associated with lower vaccination distribution (aVRR = 0.998, [0.996-0.999], p = 1.03E-04). CONCLUSIONS: Social inequalities in COVID-19 vaccines reflect an inefficient and inequitable distribution of these technologies. Future efforts to improve health should recognize the central role of social factors in impacting vaccine delivery.

Glial suppression and post-traumatic stress disorder: A cross-sectional study of 1,520 world trade center responders.

Background: Chronically re-experiencing the memory of a traumatic event might cause a glial response. This study examined whether glial activation would be associated with PTSD in a study of responders present after the 9/11 World Trade Center attacks without comorbid cerebrovascular disease. Methods: Plasma was retrieved from 1,520 WTC responders and stored for a cross-sectional sample of responders of varying levels of exposure and PTSD. Plasma levels (pg/ml) of glial fibrillary acidic protein (GFAP) were assayed. Because stroke and other cerebrovascular diseases cause distributional shifts in GFAP levels, multivariable-adjusted finite mixture models analyzed GFAP distributions in responders with and without possible cerebrovascular disease. Results: Responders were aged 56.3 years and primarily male; 11.07% (n = 154) had chronic PTSD. Older age was associated with increased GFAP, whereas higher body mass was associated with decreased GFAP. Multivariable-adjusted finite mixture models revealed that severe re-experiencing trauma from 9/11 was associated with lower GFAP (B = -0.558, p = 0.003). Conclusion: This study presents evidence of reduced plasma GFAP levels among WTC responders with PTSD. Results suggest re-experiencing traumatic events might cause glial suppression.

Explainable automated evaluation of the clock drawing task for memory impairment screening.

Introduction: The clock drawing task (CDT) is frequently used to aid in detecting cognitive impairment, but current scoring techniques are time-consuming and miss relevant features, justifying the creation of an automated quantitative scoring approach. Methods: We used computer vision methods to analyze the stored scanned images (N = 7,109), and an intelligent system was created to examine these files in a study of aging World Trade Center responders. Outcomes were CDT, Montreal Cognitive Assessment (MoCA) score, and incidence of mild cognitive impairment (MCI). Results: The system accurately distinguished between previously scored CDTs in three CDT scoring categories: contour (accuracy = 92.2%), digits (accuracy = 89.1%), and clock hands (accuracy = 69.1%). The system reliably predicted MoCA score with CDT scores removed. Predictive analyses of the incidence of MCI at follow-up outperformed human-assigned CDT scores. Discussion: We created an automated scoring method using scanned and stored CDTs that provided additional information that might not be considered in human scoring.

It Runs in the Family: Testing for Longitudinal Family Flynn Effects.

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that children in families with later-born mothers had higher average PIAT math scores, and lower average reading comprehension scores and growth, in young and middle childhood. Children in families where the first child was born later had higher average PIAT math, reading recognition, and reading comprehension scores, as well as larger developmental growth. The latter family-level Flynn effects were of higher magnitudes than the usual individual-level Flynn effect found in previous studies. Our results, showing family level-intercept and slope Flynn effects for both maternal birthyear and first child birthyear, have implications for research aiming to explain the Flynn effect.

Plasma amyloid beta 40/42, phosphorylated tau 181, and neurofilament light are associated with cognitive impairment and neuropathological changes among World Trade Center responders: A prospective cohort study of exposures and cognitive aging at midlife.

Introduction: World Trade Center (WTC) responders are experiencing a high risk of mild cognitive impairment (MCI) and dementia, though the etiology remains inadequately characterized. This study investigated whether WTC exposures and chronic post-traumatic stress disorder (PTSD) were correlated with plasma biomarkers characteristic of Alzheimer's disease (AD) neuropathology. Methods: Eligible participants included WTC-exposed individuals with a baseline cognitive assessment and available plasma sample. We examined levels of the amyloid beta (Aß)40/42 ratio, phosphorylated tau 181 (p-tau181), and neurofilament light chain (NfL) and associations with a WTC exposures (duration on site ≥15 weeks, dust cloud), the PTSD Symptom Checklist for Diagnostic and Statistical Manual of Mental Disorders, 4th edition PTSD, and classification of amyloid/tau/neurodegeneration (AT[N]) profiles. Multinomial logistic regressions assessed whether biomarkers predicted increased risk of MCI or dementia. Results: Of 1179 eligible responders, 93.0% were male, mean (standard deviation) age 56.6 years (7.8). Aß40/42, p-tau181, and NfL intercorrelated and increased with age. In subgroup analyses of responders with available neuroimaging data (n = 75), Aß40/42 and p-tau181 were further associated with decreased hippocampal volume (Spearman's ρ = -0.3). Overall, 58.08% of responders with dementia had ≥1 elevated biomarker, and 3.45% had elevations across all biomarkers. In total, 248 (21.05%) had MCI and 70 (5.94%) had dementia. Increased risk of dementia was associated with plasma AT(N) profile T+ or A+N+. Exposure on site ≥15 weeks was independently associated with T+ (adjusted risk ratio [aRR] = 1.03 [1.01-1.05], P = 0.009), and T+N+ profile (aRR = 2.34 [1.12-4.87]). The presence of PTSD was independently associated with risk of A+ (aRR = 1.77 [1.11-2.82]). Discussion: WTC exposures and chronic PTSD are associated with plasma biomarkers consistent with neurodegenerative disease.

Semiquantitative Approach to Amyloid Positron Emission Tomography Interpretation in Clinical Practice.

Objective Amyloid positron emission tomography (PET) plays a vital role in the in vivo detection of ß-amyloid accumulation in Alzheimer's disease. Increasingly, trainees and infrequent readers are relying on semiquantitative analyses to support clinical diagnostic efforts. Our objective was to determine if the visual assessment of amyloid PET may be facilitated by relying on semiquantitative analysis. Methods We conducted a retrospective review of [ 18 F]-florbetaben PET/computed tomographies (CTs) from 2016 to 2018. Visual interpretation to determine Aß+ status was conducted by two readers blinded to each other's interpretation. Scans were then post-processed utilizing the MIMneuro software, which generated regional-based semiquantitative Z-scores indicating cortical Aß-burden. Results Of 167 [ 18 F]-florbetaben PET/CTs, 92/167 (reader-1) and 101/167 (reader-2) were positive for amyloid deposition (agreement = 92.2%, κ = 0.84). Additional nine scans were identified as possible Aß-positive based solely on semiquantitative analyses. Largest semiquantitative differences were identified in the left frontal lobe (Z = 7.74 in Aß + ; 0.50 in Aß - ). All unilateral regions showed large statistically significant differences in Aß-burden ( P ≤ 2.08E-28). Semiquantitative scores were highly sensitive to Aß+ status and accurate in their ability to identify amyloid positivity, defined as a positive scan by both readers (AUC ≥ 0.90 [0.79-1.00]). Spread analyses suggested that amyloid deposition was most severe in the left posterior cingulate gyrus. The largest differences between Aß +/Aß- were in the left frontal lobe. Analyses using region-specific cutoffs indicated that the presence of amyloid in the temporal and anterior cingulate cortex, while exhibiting relatively low Z-scores, was most common. Conclusion Visual assessment and semiquantitative analysis provide highly congruent results, thereby enhancing reader confidence and improving scan interpretation. This is particularly relevant, given recent advances in amyloid-targeting disease-modifying therapeutics.

Polygenic risk scores for asthma and allergic disease associate with COVID-19 severity in 9/11 responders.

BACKGROUND: Genetic factors contribute to individual differences in the severity of coronavirus disease 2019 (COVID-19). A portion of genetic predisposition can be captured using polygenic risk scores (PRS). Relatively little is known about the associations between PRS and COVID-19 severity or post-acute COVID-19 in community-dwelling individuals. METHODS: Participants in this study were 983 World Trade Center responders infected for the first time with SARS-CoV-2 (mean age at infection = 56.06; 93.4% male; 82.7% European ancestry). Seventy-five (7.6%) responders were in the severe COVID-19 category; 306 (31.1%) reported at least one post-acute COVID-19 symptom at 4-week follow-up. Analyses were adjusted for population stratification and demographic covariates. FINDINGS: The asthma PRS was associated with severe COVID-19 category (odds ratio [OR] = 1.61, 95% confidence interval: 1.17-2.21) and more severe COVID-19 symptomatology (ß = .09, p = .01), independently of respiratory disease diagnosis. Severe COVID-19 category was also associated with the allergic disease PRS (OR = 1.97, [1.26-3.07]) and the PRS for COVID-19 hospitalization (OR = 1.35, [1.01-1.82]). PRS for coronary artery disease and type II diabetes were not associated with COVID-19 severity. CONCLUSION: Recently developed polygenic biomarkers for asthma, allergic disease, and COVID-19 hospitalization capture some of the individual differences in severity and clinical course of COVID-19 illness in a community population.