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

Clouston, Sean; Kritikos, Minos; Deri, Yael; Horton, Megan; Pellecchia, Alison C.; Santiago-Michels, Stephanie; Carr, Melissa; Gandy, Sam; Sano, Mary; Bromet, Evelyn J.; Lucchini, Roberto; Luft, Benjamin J.

doi:10.1016/j.ibmed.2021.100032

Cited by 6 publications

(2 citation statements)

References 43 publications

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“…The presence of any of these activities was thought to amplify exposure effects unless PPE was used; thus, we calculated a unit-weighted sum of these activities, to make an ordinal exposure variable with 5 distinct categories ranging from low (score, 1) to severe (score, 5) exposure. To validate and accentuate our expert-scaling scoring schema for high-exposure categories, we also used a validated artificial neural network protocol 18 , 19 to define a novel empirically derived high-exposure algorithm (eAppendix 1 in Supplement 1 ). Finally, consistent with a prior study, 14 we split the neural network moderate- and high-exposure categories based on working for at least 15 weeks on or adjacent to Ground Zero to create an ordinal exposure variable with 5 categories ranging from low (score, 1) to severe (score, 5) exposure.…”

Section: Methodsmentioning

confidence: 99%

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

Clouston,

Mann,

Meliker

et al. 2024

JAMA Netw Open

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ImportanceReports 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.ObjectiveTo 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 ParticipantsThis 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.ExposuresExposure 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 MeasuresIncidence of all-cause dementia before age 65 years was the primary outcome. Dementia was diagnosed following standard guidelines relying on repeated measures of cognition.ResultsOf 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 &lt; .001; mean risk difference, 9.74 [95% CI, 2.94-32.32] per 1000 person-years; P &lt; .001).Conclusions and RelevanceIn 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.

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Section: Methodsmentioning

confidence: 99%

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

Clouston,

Mann,

Meliker

et al. 2024

JAMA Netw Open

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“…Neurodegeneration in WTC responders does not fit a pattern consistent with known ADRD. 25,26 Noting that, we previously improved our cognitive profiling efforts by applying a deep learning approach to data from neuroimaging 27 and cognitive impairment diagnoses to estimate the risk of cortical atrophy for WTC responders. 28 This classification algorithm allows researchers to study and monitoring the potential progression of WTC-related neurodegenerative disease in this population using the results of cognitive testing when lacking intrusive and expensive methods such as structural neuroimaging and molecular diagnosis.…”

mentioning

confidence: 99%

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

Chen,

Ismail,

Mann

et al. 2023

J Geriatr Psychiatry Neurol

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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.

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Cognitive impact of exposure to airborne particles captured by brain imaging

Azmoun

Diaz

Tang

et al. 2022

Advances in Neurotoxicology

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

Cited by 6 publications

References 43 publications

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

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

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

Cognitive impact of exposure to airborne particles captured by brain imaging

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