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. 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). 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. 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. 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. 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). 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.
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