Incidence of Dementia Before Age 65 Years Among World Trade Center Attack Responders.

Importance: Reports suggest that the individuals who served in rescue operations following the terrorist attacks on the World Trade Center (WTC) have poorer brain health than expected. Objective: To assess the incidence of dementia before age 65 years in a prospective study of WTC responders and to compare incidence among responders with severe exposures to debris vs responders not exposed to building debris or who wore personalized protective equipment (PPE). Design, Setting, and Participants: This prospective cohort study was conducted from November 1, 2014, to January 1, 2023, in an academic medical monitoring program available to verified WTC responders residing on Long Island, New York. Responders 60 years of age or younger without dementia at the time of their first cognitive assessment were followed up every 18 months, on average, for up to 5 years. Exposures: Exposure severity was based on responses to a detailed questionnaire of WTC exposures and exposure-related activities that included exposures to fine particulate dust and potentially neurotoxic debris, duration of work, and the use of PPE. Exposure level was divided into 5 categories ranging from low to severe. Main Outcomes and Measures: Incidence of all-cause dementia before age 65 years was the primary outcome. Dementia was diagnosed following standard guidelines relying on repeated measures of cognition. Results: Of 9891 responders, 5010 were eligible for inclusion in this study of cognitive function (median [IQR] age, 53 [48-57] years; 4573 [91.3%] male). There were 228 cases of dementia identified during 15 913.1 person-years of follow-up. Increasing WTC exposure severity was associated with incremental increases in the incidence rate of dementia per 1000 person-years (low, 2.95 [95% CI, 1.07-11.18]; mild, 12.16 [95% CI, 10.09-14.79]; moderate, 16.53 [95% CI, 13.30-20.81]; high, 30.09 [95% CI, 21.35-43.79]; and severe, 42.37 [95% CI, 24.86-78.24]). Adjusting for social, demographic, and relevant medical factors, each unit increase in exposure severity was associated with increased incidence of dementia (adjusted hazard ratio, 1.42 [95% CI, 1.18-1.71]; P < .001; mean risk difference, 9.74 [95% CI, 2.94-32.32] per 1000 person-years; P < .001). Conclusions and Relevance: In this cohort study of WTC responders who survived these unique exposures and participated in a longitudinal follow-up study of cognition from 2014 through 2022, when compared with responders with the lowest exposure levels or responders who used PPE, more severe exposure to dust or debris was significantly associated with a higher risk of dementia before 65 years of age. This study suggests that the reliable use of PPE might help prevent the onset of dementia before age 65 years among individuals exposed to an uncontrolled building collapse. Future research is warranted to determine cerebral biomarkers for individuals with exposure-associated dementia.

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.

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.

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.

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.

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.

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.

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.

The Impact of World Trade Center Related Medical Conditions on the Severity of COVID-19 Disease and Its Long-Term Sequelae.

The individuals who served our country in the aftermath of the attacks on the World Trade Center (WTC) following the attacks of 11 September 2001 have, since then, been diagnosed with a number of conditions as a result of their exposures. In the present study, we sought to determine whether these conditions were risk factors for increased COVID-19 disease severity within a cohort of N = 1280 WTC responders with complete information on health outcomes prior to and following COVID-19 infection. We collected data on responders diagnosed with COVID-19, or had evidence of receiving positive SARS-CoV-2 polymerase chain reaction or antigen testing, or were asymptomatic but had IgG positive antibody testing. The presence of post-acute COVID-19 sequelae was measured using self-reported symptom severity scales. Analyses revealed that COVID-19 severity was associated with age, Black race, obstructive airway disease (OAD), as well as with worse self-reported depressive symptoms. Similarly, post-acute COVID-19 sequelae was associated with initial analysis for COVID-19 severity, upper respiratory disease (URD), gastroesophageal reflux disease (GERD), OAD, heart disease, and higher depressive symptoms. We conclude that increased COVID-19 illness severity and the presence of post-acute COVID-19 sequelae may be more common in WTC responders with chronic diseases than in those responders without chronic disease processes resulting from exposures at the WTC disaster.

Reduced cerebellar cortical thickness in World Trade Center responders with cognitive impairment.

Prior research has demonstrated high levels of cognitive and physical functional impairments in World Trade Center (WTC) responders. A follow-up neuroimaging study identified changes to white matter connectivity within the cerebellum in responders with cognitive impairment (CI). In the first study to examine cerebellar cortical thickness in WTC responders with CI, we fielded a structural magnetic resonance imaging protocol. WTC responders (N = 99) participated in a structural magnetic resonance imaging (MRI) study, of whom 48 had CI. Participants with CI did not differ demographically or by intracranial volume when compared to cognitively unimpaired participants. MRIs were processed using the CERES imaging pipeline; bilateral cortical thickness in 12 cerebellar lobules was reported. Analyses were completed comparing mean cerebellar cortical thickness across groups. Lobules were examined to determine the location and functional correlates of reduced cerebellar cortical thickness. Multivariable-adjusted analyses accounted for the false discovery rate. Mean cerebellar cortical thickness was reduced by 0.17 mm in responders with CI. Decrements in cerebellar cortical thickness were symmetric and located in the Cerebellar Crus (I and II), and in Lobules IV, VI, VIIb, VIIIa, VIIIb, and IX. Cerebellar cortical thickness was associated with episodic memory, response speed, and tandem balance. WTC responders with CI had evidence of reduced cerebellar cortical thickness that was present across lobules in a pattern unique to this cohort.

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.

A cortical thinning signature to identify World Trade Center responders with possible dementia.

Introduction: World Trade Center (WTC) responders have a high risk of early-onset cognitive impairment (CI), but little is known about the etiology including the extent to which CI in WTC responders is accompanied by cortical atrophy as is common in progressive diseases causing age-related CI such as Alzheimer's disease and related dementias. In the current study, we entrained an artificial neural network (ANN) to determine the accuracy of cortical thickness (CTX) on magnetic resonance imaging to identify World Trade Center responders at midlife (aged 44-65 years) with possible dementia. Methods: A total of 119 WTC responders (57 with CI and 62 with intact cognition) underwent a structural MRI scanning protocol including T1-weighted MPRAGE as part of two imaging studies. The discovery study was divided into training and validation samples, while a second replication sample was used. An ANN was trained using regional CTX measured across 34 unilateral regions of interest (ROIs) using Freesurfer software and 'Desikan-Killiany' brain atlas. The discovery sample was used for model development, and the replication sample was used to evaluate predictive accuracy. Results: In the WTC responder cohort, the ANN algorithm showed high discrimination performance for CI. The ANN model using regional CTX data from both hemispheres achieved an area under the receiver operating characteristic curve (AUC) of 0.96 95% C.I. = [0.91-1.00] (Accuracy = 96.0%, Precision = 97.8%, Recall = 95.8%, Sensitivity = 95.8%, Specificity = 98.0%, F1 = 96.8%) for the discovery sample and AUC = 0.90 [0.70-1.00] (Accuracy = 90.0%, Precision = 90.0%, Sensitivity = 90.0%, Specificity = 90.0%, F1 = 90.0%) in the replication sample. Conclusion: Analysis of bilateral regional CTX data derived from T1-weighted MPRAGE images by ANN analysis demonstrated excellent accuracy in distinguishing WTC responders with early-onset CI.

Cortical complexity in world trade center responders with chronic posttraumatic stress disorder.

Approximately 23% of World Trade Center (WTC) responders are experiencing chronic posttraumatic stress disorder (PTSD) associated with their exposures at the WTC following the terrorist attacks of 9/11/2001, which has been demonstrated to be a risk factor for cognitive impairment raising concerns regarding their brain health. Cortical complexity, as measured by analyzing Fractal Dimension (FD) from T1 MRI brain images, has been reported to be reduced in a variety of psychiatric and neurological conditions. In this report, we hypothesized that FD would be also reduced in a case-control sample of 99 WTC responders as a result of WTC-related PTSD. The results of our surface-based morphometry cluster analysis found alterations in vertex clusters of complexity in WTC responders with PTSD, with marked reductions in regions within the frontal, parietal, and temporal cortices, in addition to whole-brain absolute bilateral and unilateral complexity. Furthermore, region of interest analysis identified that the magnitude of changes in regional FD severity was associated with increased PTSD symptoms (reexperiencing, avoidance, hyperarousal, negative affect) severity. This study confirms prior findings on FD and psychiatric disorders and extends our understanding of FD associations with posttraumatic symptom severity. The complex and traumatic experiences that led to WTC-related PTSD were associated with reductions in cortical complexity. Future work is needed to determine whether reduced cortical complexity arose prior to, or concurrently with, onset of PTSD.

A deep learning approach for monitoring parietal-dominant Alzheimer's disease in World Trade Center responders at midlife.

Little is known about the characteristics and causes of early-onset cognitive impairment. Responders to the 2001 New York World Trade Center disaster represent an ageing population that was recently shown to have an excess prevalence of cognitive impairment. Neuroimaging and molecular data demonstrate that a subgroup of affected responders may have a unique form of parietal-dominant Alzheimer's Disease. Recent neuropsychological testing and artificial intelligence approaches have emerged as methods that can be used to identify and monitor subtypes of cognitive impairment. We utilized data from World Trade Center responders participating in a health monitoring program and applied a deep learning approach to evaluate neuropsychological and neuroimaging data to generate a cortical atrophy risk score. We examined risk factors associated with the prevalence and incidence of high risk for brain atrophy in responders who are now at midlife. Training was conducted in a randomly selected two-thirds sample (N = 99) enrolled using of the results of a structural neuroimaging study. Testing accuracy was estimated for each training cycle in the remaining third subsample. After training was completed, the scoring methodology that was generated was applied to longitudinal data from 1441 World Trade Center responders. The artificial neural network provided accurate classifications of these responders in both the testing (Area Under the Receiver Operating Curve, 0.91) and validation samples (Area Under the Receiver Operating Curve, 0.87). At baseline and follow-up, responders identified as having a high risk of atrophy (n = 378) showed poorer cognitive functioning, most notably in domains that included memory, throughput, and variability as compared to their counterparts at low risk for atrophy (n = 1063). Factors associated with atrophy risk included older age [adjusted hazard ratio, 1.045 (95% confidence interval = 1.027-1.065)], increased duration of exposure at the WTC site [adjusted hazard ratio, 2.815 (1.781-4.449)], and a higher prevalence of post-traumatic stress disorder [aHR, 2.072 (1.408-3.050)]. High atrophy risk was associated with an increased risk of all-cause mortality [adjusted risk ratio, 3.19 (1.13-9.00)]. In sum, the high atrophy risk group displayed higher levels of previously identified risk factors and characteristics of cognitive impairment, including advanced age, symptoms of post-traumatic stress disorder, and prolonged duration of exposure to particulate matter. Thus, this study suggests that a high risk of brain atrophy may be accurately monitored using cognitive data.

Selective hippocampal subfield volume reductions in World Trade Center responders with cognitive impairment.

INTRODUCTION: The objective of this study was to investigate associations between dementia in World Trade Center (WTC) responders and in vivo volumetric measures of hippocampal subfield volumes in WTC responders at midlife. METHODS: A sample of 99 WTC responders was divided into dementia and unimpaired groups. Participants underwent structural T1-weighted magnetic resonance imaging. Volumetric measures included the overall hippocampus and eight subfields. Regression models examined volumetric measure of interest adjusting for confounders including intracranial volume. RESULTS: Dementia was associated with smaller hippocampal volume and with reductions across hippocampal subfields. Smaller hippocampal subfield volumes were associated with longer cumulative time worked at the WTC. Domain-specific cognitive performance was associated with lower volumetric measures across hippocampal subregions. CONCLUSIONS: This is the first study to investigate hippocampal subfield volumes in a sample of WTC responders at midlife. Selective hippocampal subfield volume reductions suggested abnormal cognition that were associated with WTC exposure duration.

Reduced cortical thickness in World Trade Center responders with cognitive impairment.

INTRODUCTION: This study examined cortical thickness (CTX) in World Trade Center (WTC) responders with cognitive impairment (CI). METHODS: WTC responders (N = 99) with/without CI, recruited from an epidemiologic study, completed a T1-MPRAGE protocol. CTX was automatically computed in 34 regions of interest. Region-based and surface-based morphometry examined CTX in CI versus unimpaired responders. CTX was automatically computed in 34 regions of interest. Region-based measures were also compared to published norms. RESULTS: Participants were 55.8 (SD = 0.52) years old; 48 had CI. Compared to unimpaired responders, global mean CTX was reduced in CI and across 21/34 cortical subregions. Surface-based analyses revealed reduced CTX across frontal, temporal, and parietal lobes when adjusting for multiple comparisons. Both CI and unimpaired WTC groups had reduced CTX in the entorhinal and temporal cortices compared to published normative data. DISCUSSION: Results from the first structural magnetic resonance imaging study in WTC responders identified reduced CTX consistent with a neurodegenerative disease of unknown etiology.