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.

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.

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.

Daily Sleep-Stress Reactivity and Functional Impairment in World Trade Center Responders.

BACKGROUND: How sleep is impacted by stress ("sleep reactivity to stress") and how stress is impacted by sleep ("stress reactivity to sleep") are trait-like characteristics of individuals that predict depression, anxiety, and insomnia. However, pathways between reactivity and functional impairment (e.g., impairment in social relationships and interpersonal functioning) have not been explored, which may be a critical pathway in understanding the link between reactivity and the development of psychological disorders. PURPOSE: We examined associations between reactivity and changes in functional impairment among a cohort of 9/11 World Trade Center responders. METHODS: Data from 452 responders (Mage = 55.22 years; 89.4% male) were collected between 2014 and 2016. Four baseline sleep and stress reactivity indices (i.e., sleep duration and efficiency reactivity to stress; stress reactivity to sleep duration and efficiency) were calculated from 14 days of sleep and stress data using random slopes from multilevel models. Functional impairment was assessed approximately 1 year and 2 years after baseline via semi-structured interviews. Latent change score analyses examined associations between baseline reactivity indices and changes in functional impairment. RESULTS: Greater baseline sleep efficiency reactivity to stress was associated with decreases in functioning (ß = -0.05, p = .039). In addition, greater stress reactivity to sleep duration (ß = -0.08, p = .017) and sleep efficiency (ß = -0.22, p < .001) was associated with lower functioning at timepoint one. CONCLUSION: People who are more reactive to daily fluctuations in stress and sleep have poorer interpersonal relationships and social functioning. Identifying individuals with high reactivity who could benefit from preventative treatment may foster better social integration.

How sleep is impacted by stress ("sleep reactivity to stress") and how stress is impacted by sleep ("stress reactivity to sleep") are trait-like characteristics of individuals that may contribute to an individual's risk of developing of psychological disorders, such as depression, anxiety, and insomnia. It is possible that individuals with high sleep-stress reactivity are more likely to experience long-term functional impairment (e.g., impairment in social relationships and interpersonal functioning)­a predisposing factor for psychological disorders, yet this pathway has not been explored. Therefore, we examined associations between sleep-stress reactivity and changes in functional impairment across a 1-year period in a large sample of 9/11 World Trade Center responders. The study results suggest that 9/11 World Trade Center responders who are more reactive to daily fluctuations in stress and sleep have poorer interpersonal relationships and social functioning. Identifying individuals with high sleep-stress reactivity who could benefit from preventative treatment may foster better social integration.

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.

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.

Genetic Liability, Exposure Severity, and Post-Traumatic Stress Disorder Predict Cognitive Impairment in World Trade Center Responders.

BACKGROUND: There is a high incidence of cognitive impairment among World Trade Center (WTC) responders, comorbid with post-traumatic stress disorder (PTSD). Yet, it remains unknown whether genetic liability for Alzheimer's disease, PTSD, educational attainment, or for a combination of these phenotypes, is associated with cognitive impairment in this high-risk population. Similarly, whether the effects of genetic liability are comparable to PTSD and indicators of exposure severity remains unknown. OBJECTIVE: In a study of 3,997 WTC responders, polygenic scores for Alzheimer's disease, PTSD, and educational attainment were used to test whether genome-wide risk for one or more of these phenotypes is associated with cognitive impairment, controlling for population stratification, while simultaneously estimating the effects of demographic factors and indicators of 9/11 exposure severity, including symptoms of PTSD. RESULTS: Polygenic scores for Alzheimer's disease and educational attainment were significantly associated with an increase and decrease, respectively, in the hazard rate of mild cognitive impairment. The polygenic score for Alzheimer's disease was marginally associated with an increase in the hazard rate of severe cognitive impairment, but only age, exposure severity, and symptoms of PTSD were statistically significant predictors. CONCLUSION: These results add to the emerging evidence that many WTC responders are suffering from mild cognitive impairments that resemble symptoms of Alzheimer's disease, as genetic liability for Alzheimer's disease predicted incidence of mild cognitive impairment. However, compared to polygenic scores, effect sizes were larger for PTSD and the type of work that responders completed during rescue and recovery efforts.

Discovery and replication of blood-based proteomic signature of PTSD in 9/11 responders.

Proteomics provides an opportunity to develop biomarkers for the early detection and monitoring of post-traumatic stress disorder (PTSD). However, research to date has been limited by small sample sizes and a lack of replication. This study performed Olink Proseek Multiplex Platform profiling of 81 proteins involved in neurological processes in 936 responders to the 9/11 disaster (mean age at blood draw = 55.41 years (SD = 7.93), 94.1% white, all men). Bivariate correlations and elastic net regressions were used in a discovery subsample to identify concurrent associations between PTSD symptom severity and the profiled proteins, and to create a multiprotein composite score. In hold-out subsamples, nine bivariate associations between PTSD symptoms and differentially expressed proteins were replicated: SKR3, NCAN, BCAN, MSR1, PVR, TNFRSF21, DRAXIN, CLM6, and SCARB2 (|r| = 0.08-0.17, p < 0.05). There were three replicated bivariate associations between lifetime PTSD diagnosis and differentially expressed proteins: SKR3, SIGLEC, and CPM (OR = 1.38-1.50, p < 0.05). The multiprotein composite score retained 38 proteins, including 10/11 proteins that replicated in bivariate tests. The composite score was significantly associated with PTSD symptom severity (ß = 0.27, p < 0.001) and PTSD diagnosis (OR = 1.60, 95% CI: 1.17-2.19, p = 0.003) in the hold-out subsample. Overall, these findings suggest that PTSD is characterized by altered expression of several proteins implicated in neurological processes. Replicated associations with TNFRSF21, CLM6, and PVR support the neuroinflammatory signature of PTSD. The multiprotein composite score substantially increased associations with PTSD symptom severity over individual proteins. If generalizable to other populations, the current findings may inform the development of PTSD biomarkers.

Genomic Confirmation of Borrelia garinii, United States.

Lyme disease is a multisystem disorder primarily caused by Borrelia burgdorferi sensu lato. However, B. garinii, which has been identified on islands off the coast of Newfoundland and Labrador, Canada, is a cause of Lyme disease in Eurasia. We report isolation and whole-genome nucleotide sequencing of a B. garinii isolate from a cotton mouse (Peromyscus gossypinus) in South Carolina, USA. We identified a second B. garinii isolate from the same repository. Phylogenetic analysis does not associate these isolates with the previously described isolates of B. garinii from Canada.

World Trade Center Site Exposure Duration Is Associated with Hippocampal and Cerebral White Matter Neuroinflammation.

Responders to the World Trade Center (WTC) attacks on 9/11/2001 inhaled toxic dust and experienced severe trauma for a prolonged period. Studies report that WTC site exposure duration is associated with peripheral inflammation and risk for developing early-onset dementia (EOD). Free Water Fraction (FWF) can serve as a biomarker for neuroinflammation by measuring in vivo movement of free water across neurons. The present case-controlled study aimed to examine associations between WTC site exposure duration as well as EOD status with increased hippocampal and cerebral neuroinflammation. Ninety-nine WTC responders (mean age of 56) were recruited between 2017 and 2019 (N = 48 with EOD and 51 cognitively unimpaired). Participants were matched on age, sex, occupation, race, education, and post-traumatic stress disorder (PTSD) status. Participants underwent neuroimaging using diffusion tensor imaging protocols for FWF extraction. Region of interest (ROI) analysis and correlational tractography explored topographical distributions of FWF associations. Apolipoprotein-e4 allele (APOEε4) status was available for most responders (N = 91). Hippocampal FWF was significantly associated with WTC site exposure duration (r = 0.30, p = 0.003), as was cerebral white matter FWF (r = 0.20, p = 0.044). ROI analysis and correlational tractography identified regions within the limbic, frontal, and temporal lobes. Hippocampal FWF and its association with WTC exposure duration were highest when the APOEε4 allele was present (r = 0.48, p = 0.039). Our findings demonstrate that prolonged WTC site exposure is associated with increased hippocampal and cerebral white matter neuroinflammation in WTC responders, possibly exacerbated by possession of the APOEε4 allele.

Longitudinal associations between PTSD and sleep disturbances among World Trade Center responders.

OBJECTIVE/BACKGROUND: Post-traumatic stress disorder (PTSD) is characterized by substantial disruptions in sleep quality, continuity, and depth. Sleep problems also may exacerbate PTSD symptom severity. Understanding how PTSD and sleep may reinforce one another is critical for informing effective treatments. PATIENTS/METHODS: In a sample of 452 World Trade Center 9/11 responders (mean age = 55.22, 89.4% male, 66.1% current or former police), we examined concurrent and cross-lagged associations between PTSD symptom severity, insomnia symptoms, nightmares, and sleep quality at 3 time points ∼1 year apart. Data were analyzed using random intercept cross-lagged panel models. RESULTS: PTSD symptom severity and sleep variables were relatively stable across time (intraclass correlation coefficients: 0.63 to 0.84). Individuals with more insomnia symptoms, more nightmares, and poorer sleep quality had greater PTSD symptom severity, on average. Within-person results revealed that greater insomnia symptoms and nightmares at Time 1 were concurrently associated with greater PTSD symptoms at Time 1. Insomnia symptoms were also concurrently associated with PTSD symptoms at Times 2 and 3, respectively. Cross-lagged and autoregressive results revealed that PTSD symptoms and nightmares predicted nightmares at the next timepoint. CONCLUSIONS: Overall, results suggest PTSD and sleep problems may be linked at the same point in time but may not always influence each other longitudinally. Further, individuals who experience more sleep disturbances on average may suffer from more debilitating PTSD. Evidence-based treatments for PTSD may consider incorporating treatment of underlying sleep disturbances and nightmares.

The World Trade Center Health Program: an introduction to best practices.

More than 20 years have elapsed since the September 11, 2001 (9/11) terrorist attacks on the World Trade Center (WTC), Pentagon and at Shanksville, PA. Many persons continue to suffer a variety of physical and mental health conditions following their exposures to a mixture of incompletely characterized toxicants and psychological stressors at the terrorist attack sites. Primary care and specialized clinicians should ask patients who may have been present at any of the 9/11 sites about their 9/11 exposures, especially patients with cancer, respiratory symptoms, chronic rhinosinusitis, gastroesophageal reflux disease, psychiatric symptoms, and substance use disorders. Clinicians, especially those in the NY metropolitan area, should know how to evaluate, diagnose, and treat patients with conditions that could be associated with exposure to the 9/11 attacks and its aftermath. As such, this issue of Archives contains a series of updates to clinical best practices relevant to medical conditions whose treatment is covered by the WTC Health Program. This first paper in the 14-part series describes the purpose of this series, defines the WTC Health Program and its beneficiaries, and explains how relevant Clinical Practice Guidelines were identified. This paper also reminds readers that because physical and mental health conditions are often intertwined, a coordinated approach to care usually works best and referral to health centers affiliated with the WTC Health Program may be necessary, since all such Centers offer multidisciplinary care.

World Trade Center responders in their own words: predicting PTSD symptom trajectories with AI-based language analyses of interviews.

BACKGROUND: Oral histories from 9/11 responders to the World Trade Center (WTC) attacks provide rich narratives about distress and resilience. Artificial Intelligence (AI) models promise to detect psychopathology in natural language, but they have been evaluated primarily in non-clinical settings using social media. This study sought to test the ability of AI-based language assessments to predict PTSD symptom trajectories among responders. METHODS: Participants were 124 responders whose health was monitored at the Stony Brook WTC Health and Wellness Program who completed oral history interviews about their initial WTC experiences. PTSD symptom severity was measured longitudinally using the PTSD Checklist (PCL) for up to 7 years post-interview. AI-based indicators were computed for depression, anxiety, neuroticism, and extraversion along with dictionary-based measures of linguistic and interpersonal style. Linear regression and multilevel models estimated associations of AI indicators with concurrent and subsequent PTSD symptom severity (significance adjusted by false discovery rate). RESULTS: Cross-sectionally, greater depressive language (ß = 0.32; p = 0.049) and first-person singular usage (ß = 0.31; p = 0.049) were associated with increased symptom severity. Longitudinally, anxious language predicted future worsening in PCL scores (ß = 0.30; p = 0.049), whereas first-person plural usage (ß = -0.36; p = 0.014) and longer words usage (ß = -0.35; p = 0.014) predicted improvement. CONCLUSIONS: This is the first study to demonstrate the value of AI in understanding PTSD in a vulnerable population. Future studies should extend this application to other trauma exposures and to other demographic groups, especially under-represented minorities.

Physical Functional Impairment and the Risk of Incident Mild Cognitive Impairment in an Observational Study of World Trade Center Responders.

Background and Objectives: Posttraumatic stress disorder (PTSD) has been linked to increased risk of cognitive dysfunction and physical functional impairment (PFI). The objective of this prospective cohort study was to examine whether PFI was associated with increased risk of incident mild cognitive impairment (MCI) among World Trade Center (WTC) responders with PTSD. We hypothesized that responders with PTSD would have an elevated risk of incident MCI and that PFI would mediate this increase. Methods: We examined responder participants in the WTC Aging Study whose baseline physical assessments were completed by May 2016-April 2017 and were followed up at least once before December 2019. Those without complete demographic, medical, or behavioral data were excluded. PFI was assessed using measures of upper body strength (maximal handgrip strength [HGS]) and lower extremity physical functioning (Short Physical Performance Battery). PTSD was rated using a diagnostic interview and symptom checklist; MCI and dementia were assessed using the Montreal Cognitive Assessment and diagnosed using the National Institute on Aging-Alzheimer's Association criteria. Group differences and longitudinal comparisons were examined. Cox proportional hazards models were evaluated from time to incident MCI and conversion to dementia. A mediation analysis examined whether PFI mediated associations between PTSD and MCI. Results: Within the sample of 2,687 WTC responders, 324 (12.06%, 95% CI = [10.83-13.29]) had lower extremity PFI. Responders with lower extremity PFI were older, had lower education and higher body mass, and were at a higher risk of pulmonary embolisms and PTSD. Responders with lower extremity PFI demonstrated lower baseline cognition and had increased hazards of MCI (multivariable-adjusted hazards ratio [aHR] = 1.55 [95% CI 1.21-1.98]); those with MCI converted to dementia more rapidly than those without PFI (2.73 [1.38-5.39] p = 0.004). In addition, each standard deviation decrease in HGS was associated with increased hazards of developing MCI (aHR = 1.35 [95% CI 1.10-1.66]). A mediation model suggested PFI played an intermediary role in the relationship between PTSD and MCI. Discussion: WTC responders with PFI demonstrated worse cognitive and behavioral outcomes, and PFI played an intermediary role in the relationship between PTSD and incident MCI, suggesting that PFI may be an early indicator of MCI in responders with PTSD. Regular monitoring of PFI should be considered among PTSD populations.

The Role of Personality in the Mental and Physical Health of World Trade Center Responders: Self- versus Informant-Reports.

Personality is linked to important health outcomes, but most prior studies have relied on self-reports, making it possible that shared-method variance explains the associations. The present study examined self- versus informant-reports of personality and multi-method outcomes. World Trade Center (WTC) responders and informants, 283 pairs, completed five-factor model personality measures and multi-method assessments of stressful events, functioning, mental disorders, 9/11-related treatment costs, BMI, and daily activity across three years. Self-reports were uniquely related to stressful events and functioning. Both self-reports and informant-reports showed incremental validity over one another for mental disorder diagnoses and treatment costs. For objective outcomes daily activity and BMI, informant-reports showed incremental validity over self-reports, accounting for all self-report variance and more. The findings suggest that informant-reports of personality provide better validity for objective health outcomes, which has implications for understanding personality and its role in mental and physical health.

Assessment of Alzheimer's Disease Imaging Biomarkers in World Trade Center Responders with Cognitive Impairment at Midlife.

Purpose Incidence of early onset neurocognitive dysfunction has been reported in World Trade Center (WTC) responders. Ongoing studies are investigating the underlying etiology, as we are concerned that an underlying risk of neurodegenerative dementia may be occurring because of their stressful and neurotoxic exposures to particulate matter when they responded to the search and rescue efforts on September 11, 2001. The purpose of this study is to report preliminary results from two ongoing positron emission tomography (PET)/magnetic resonance imaging (MRI) imaging studies investigating the presence of Alzheimer's disease (AD) biomarkers, such as ß-amyloid, tau, and neurodegeneration, and compare our findings to published norms. Methods We present findings on 12 WTC responders diagnosed with either cognitive impairment (CI) or mild cognitive impairment (MCI), now at midlife, who underwent PET/MRI brain imaging as part of ongoing studies. Six responders with CI received [ 18 F] florbetaben (FBB) to detect ß-amyloidosis and six separate responders with MCI received [ 18 F] flortaucipir (FTP) to detect tauopathy. All 12 responders underwent concomitant MRI scans for gray matter volume analysis of neurodegeneration. Results PET analysis revealed 50% FBB and 50% of FTP scans were clinically read as positive and that 50% of FTP scans identified as consistent with Braak's stage I or II. Furthermore, one responder identified as centiloid positive for AD. Gray matter volumes from MRI analyses were compared with age/sex-matched norms (Neuroquant), identifying abnormally low cortical volumes in the occipital and temporal lobes, as well as the inferior temporal gyri and the entorhinal cortex. Conclusion These preliminary results suggest that WTC responders with neurocognitive dysfunction may be at increased risk for a neurodegenerative dementia process as a result of their exposures at September 11, 2001.

The prognostic utility of personality traits versus past psychiatric diagnoses: Predicting future mental health and functioning.

Past psychiatric diagnoses are central to patient case formulation and prognosis. Recently, alternative classification models such as the Hierarchical Taxonomy of Psychopathology (HiTOP) proposed to assess traits to predict clinically-relevant outcomes. The current study directly compared personality traits and past diagnoses as predictors of future mental health and functioning in three independent, prospective samples. Regression analyses found that personality traits significantly predicted future first onsets of psychiatric disorders (ΔR2=06-.15), symptom chronicity (ΔR2=.03-.06), and functioning (ΔR2=.02-.07), beyond past and current psychiatric diagnoses. Conversely, past psychiatric diagnoses did not provide an incremental prediction of outcomes when personality traits and other concurrent predictors were already included in the model. Overall, personality traits predicted a variety of outcomes in diverse settings, beyond diagnoses. Past diagnoses were generally not informative about future outcomes when personality was considered. Together, these findings support the added value of personality traits assessment in case formulation, consistent with HiTOP model.

Myeloma precursor disease (MGUS) among rescue and recovery workers exposed to the World Trade Center disaster.

An elevated risk of myeloma precursor disease, monoclonal gammopathy of undetermined significance (MGUS), was identified among Fire Department of the City of New York (FDNY) World Trade Center (WTC)-exposed firefighters. Further investigation was needed to determine if these findings were reproducible in a more heterogeneous WTC-exposed rescue/recovery workers cohort, the Stony Brook University-General Responder Cohort GRC (SBU-GRC). MGUS risk was compared between the cohorts and to published general population estimates from Olmsted County, MN, USA. In this observational seroprevalence study, odds ratios (OR) and age-standardized risk ratios (RR) of MGUS (M-spike and light-chain-MGUS combined), M-spike, and light-chain-MGUS were estimated using logistic regression. Age-standardized prevalences were calculated for white males aged 50-79; RRs were estimated by comparing risk in the WTC-exposed cohort with the Olmsted County screened cohort. SBU-GRC had elevated odds of MGUS compared with FDNY (OR = 1.38; 95%CI = 1.00-1.89). The age-standardized prevalence of MGUS was 9.0/100 persons (95%CI = 7.5-10.6), over two-fold higher than the general population (RR = 2.08; 95%CI = 1.72-2.51); the age-standardized prevalence of light-chain-MGUS was 3.5-fold higher (RR = 3.54; 95%CI = 2.52-4.97). This study adds to mounting evidence supporting an association between WTC/environmental exposures and MGUS among rescue/recovery workers. Access to MGUS screenings for the entire WTC-exposed cohort could allow for treatment interventions that improve survival.

DTI Connectometry Analysis Reveals White Matter Changes in Cognitively Impaired World Trade Center Responders at Midlife.

BACKGROUND: More than 8% of responders who participated in the search and rescue efforts at the World Trade Center (WTC) following 9/11 developed early-onset cognitive impairment (CI). Approximately 23% were also diagnosed with chronic post-traumatic stress disorder (PTSD). OBJECTIVE: To shed light on the pathophysiology of these WTC-related conditions, we examined diffusion connectometry to identify altered white matter tracts in WTC responders with CI and/or PTSD compared to unaffected responders. METHODS: 99 WTC responders (mean age 56 years) consisting of CI-/PTSD- (n = 27), CI+/PTSD- (n = 25), CI-/PTSD+ (n = 24), and CI+/PTSD+ (n = 23) were matched on age, sex, occupation, race, and education. Cognitive status was determined using the Montreal Cognitive Assessment and PTSD status was determined using the DSM-IV SCID. Diffusion tensor imaging was acquired on a 3T Siemens Biograph mMR scanner. Connectometry analysis was used to examine whole-brain tract-level differences in white matter integrity as reflected by fractional anisotropy (FA) values after adjusting for confounders. RESULTS: Analyses identified that FA was negatively correlated with CI and PTSD status in the fornix, cingulum, forceps minor of the corpus callosum and the right uncinate fasciculus. Furthermore, FA was negatively correlated with PTSD status, regardless of CI status in the superior thalamic radiation and the cerebellum. CONCLUSION: This is the first connectometry study to examine altered white matter tracts in a sample of WTC responders with CI and/or PTSD. Results from this study suggest that WTC responders with early-onset CI may be experiencing an early neurodegenerative process characterized by decreased FA in white matter tracts.