Prevalence of Mild and Severe Cognitive Impairment in World Trade Center Exposed Fire Department of the City of New York (FDNY) and General Emergency Responders.

Background: The emergency personnel who responded to the World Trade Center (WTC) attacks endured severe occupational exposures, yet the prevalence of cognitive impairment remains unknown among WTC-exposed-FDNY-responders. The present study screened for mild and severe cognitive impairment in WTC-exposed FDNY responders using objective tests, compared prevalence rates to a cohort of non-FDNY WTC-exposed responders, and descriptively to meta-analytic estimates of MCI from global, community, and clinical populations. Methods: A sample of WTC-exposed-FDNY responders (n = 343) was recruited to complete an extensive battery of cognitive, psychological, and physical tests. The prevalences of domain-specific impairments were estimated based on the results of norm-referenced tests, and the Montreal Cognitive Assessment (MoCA), Jak/Bondi criteria, Petersen criteria, and the National Institute on Aging and Alzheimer's Association (NIA-AA) criteria were used to diagnose MCI. NIA-AA criteria were also used to diagnose severe cognitive impairment. Generalized linear models were used to compare prevalence estimates of cognitive impairment to a large sample of WTC-exposed-non-FDNY responders from the General Responder Cohort (GRC; n = 7102) who completed the MoCA during a similar time frame. Result: Among FDNY responders under 65 years, the unadjusted prevalence of MCI varied from 52.57% to 71.37% depending on the operational definition of MCI, apart from using a conservative cut-off applied to MoCA total scores (18 < MoCA < 23), which yielded a markedly lower crude prevalence (24.31%) compared to alternative criteria. The prevalence of MCI was higher among WTC-exposed-FDNY-responders, compared to WTC-exposed-non-FDNY-GRC-responders (adjusted RR = 1.53, 95% C.I . = [1.24, 1.88], p < .001) and meta-analytic estimates from different global, community, and clinical populations. Following NIA-AA diagnostic guidelines, 4.96% of WTC-exposed-FDNY-responders met the criteria for severe impairments (95% CI = [2.91% to 7.82%]), a prevalence that remained largely unchanged after excluding responders over the age of 65 years. Discussion: There is a high prevalence of mild and severe cognitive impairment among WTC-responders highlighting the putative role of occupational/environmental and disaster-related exposures in the etiology of accelerated cognitive decline.

Cross-sectional association between posttraumatic stress and cognition is moderated by pulmonary functioning in world trade center responders.

BACKGROUND: Posttraumatic stress disorder (PTSD) symptomatology and poorer pulmonary function are highly prevalent psychiatric and medical conditions. In the present study, we tested for the individual, additive, and modifying associations of PTSD symptomatology and pulmonary function with cognitive performance. METHODS: In this cross-sectional study, a total of 1,401 World Trade Center (WTC) responders (mean age = 53, SD = 8 years, 92% males) participated in the study. Cogstate assessment measured cognitive performance. PTSD symptomatology was measured using the trauma-specific version of the posttraumatic stress disorder checklist (PCL-17) adapted for the WTC attacks. The 1-second forced expiratory volume and forced vital capacity (FEV1/FVC) ratio was used to measure pulmonary function. Linear regressions with cognitive performance as the outcome were conducted to assess individual, additive, and moderating associations of PTSD symptomatology and pulmonary function. RESULTS: Higher PTSD symptomatology and poorer pulmonary function were negatively associated with cognitive performance. A 10% increase on the FEV1/FVC ratio moderated the association between PTSD symptomatology and cognition, whereby its association with cognition was stronger when PTSD symptomatology was higher (est. = 0.01, 95%CI = 0.004, 0.01, p < 0.001). When stratified by responder type, these associations persisted in trained (est. = 0.01, 95%CI = 0.01, 0.02, p < 0.001), but not in non-trained (est. = 0.004, 95% C.I. = -0.01, 0.02, p = 0.39) responders. CONCLUSIONS: In the presence of higher PTSD, better pulmonary functioning is associated with better cognitive performance. Early intervention efforts to mitigate preventable cognitive decline in high-risk populations should be studied, especially since intervention in one modality may have an impact on others.

Interstitial Lung Disease and Progressive Pulmonary Fibrosis: a World Trade Center Cohort 20-Year Longitudinal Study.

PURPOSE: World Trade Center (WTC) exposure is associated with obstructive airway diseases and sarcoidosis. There is limited research regarding the incidence and progression of non-sarcoidosis interstitial lung diseases (ILD) after WTC-exposure. ILD encompasses parenchymal diseases which may lead to progressive pulmonary fibrosis (PPF). We used the Fire Department of the City of New York's (FDNY's) WTC Health Program cohort to estimate ILD incidence and progression. METHODS: This longitudinal study included 14,525 responders without ILD prior to 9/11/2001. ILD incidence and prevalence were estimated and standardized to the US 2014 population. Poisson regression modeled risk factors, including WTC-exposure and forced vital capacity (FVC), associated with ILD. Follow-up time ended at the earliest of incident diagnosis, end of study period/case ascertainment, transplant or death. RESULTS: ILD developed in 80/14,525 FDNY WTC responders. Age, smoking, and gastroesophageal reflux disease (GERD) prior to diagnosis were associated with incident ILD, though FVC was not. PPF developed in 40/80 ILD cases. Among the 80 cases, the average follow-up time after ILD diagnosis was 8.5 years with the majority of deaths occurring among those with PPF (PPF: n = 13; ILD without PPF: n = 6). CONCLUSIONS: The prevalence of post-9/11 ILD was more than two-fold greater than the general population. An exposure-response gradient could not be demonstrated. Half the ILD cases developed PPF, higher than previously reported. Age, smoking, and GERD were risk factors for ILD and PPF, while lung function was not. This may indicate that lung function measured after respirable exposures would not identify those at risk for ILD or PPF.

Association of firefighting exposures with lung function using a novel job exposure matrix (JEM).

OBJECTIVES: Characterisation of firefighters' exposures to dangerous chemicals in smoke from non-wildfire incidents, directly through personal monitoring and indirectly from work-related records, is scarce. The aim of this study was to evaluate the association between smoke particle exposures (P) and pulmonary function. METHODS: The study period spanned from January 2010 through September 2021. Routine firefighting P were estimated using fire incident characteristics, response data and emission factors from a novel job exposure matrix. Linear mixed effects modelling was employed to estimate changes in pulmonary function as measured by forced expiratory volume in one second (FEV1). Models controlled for age, race/ethnicity, height, smoking and weight. RESULTS: Every 1000 kg P was associated with 13 mL lower FEV1 (ß=-13.34; 95% CI=-13.98 to -12.70) over the entire 12-year follow-up period. When analysing exposures within 3 months before PFT measurements, 1000 kg P was associated with 27 mL lower FEV1 (ß=-26.87; 95% CI=-34.54 to -19.20). When evaluating P estimated within 3 months of a pulmonary function test (PFT), stronger associations were observed among those most highly exposed to the World Trade Center (WTC) disaster (ß=-12.90; 95% CI=-22.70 to -2.89); the association of cumulative exposures was similar for both highly and less highly exposed individuals. DISCUSSION: Smoke particle exposures were observed to have modest short-term and long-term associations with pulmonary function, particularly in those who, previously, had high levels of WTC exposure. Future work examining the association between P and pulmonary function among non-WTC exposed firefighters will be essential for disentangling the effects of ageing, routine firefighting and WTC exposures.

Normal Lung Function and Mortality in World Trade Center Responders and National Health and Nutrition Examination Survey III Participants.

Rationale: Low FEV1 is a biomarker of increased mortality. The association of normal lung function and mortality is not well described. Objectives: To evaluate the FEV1-mortality association among participants with normal lung function. Methods: A total of 10,999 Fire Department of the City of New York (FDNY) responders and 10,901 Third National Health and Nutrition Examination Survey (NHANES III) participants, aged 18-65 years with FEV1 ⩾80% predicted, were analyzed, with FEV1 percent predicted calculated using Global Lung Function Initiative Global race-neutral reference equations. Mortality data were obtained from linkages to the National Death Index. Cox proportional hazards models estimated the association between FEV1 and all-cause mortality, controlling for age, sex, race/ethnicity, smoking history, and, for FDNY, work assignment. Cohorts were followed for a maximum of 20.3 years. Measurements and Main Results: We observed 504 deaths (4.6%) of 10,999 for FDNY and 1,237 deaths (9.4% [weighted]) of 10,901 for NHANES III. Relative to FEV1 ⩾120% predicted, mortality was significantly higher for FEV1 100-109%, 90-99%, and 80-89% predicted in the FDNY cohort. In the NHANES III cohort, mortality was significantly higher for FEV1 90-99% and 80-89% predicted. Each 10% higher predicted FEV1 was associated with 15% (hazard ratio, 0.85; 95% confidence interval, 0.80-0.91) and 23% (hazard ratio, 0.77; 95% confidence interval, 0.71-0.84) lower mortality for FDNY and NHANES III, respectively. Conclusions: In both cohorts, higher FEV1 is associated with lower mortality, suggesting higher FEV1 is a biomarker of better health. These findings demonstrate that a single cross-sectional measurement of FEV1 is predictive of mortality over two decades, even when FEV1 is in the normal range.

Self-reported Cardiovascular Disease in Career Firefighters With and Without World Trade Center Exposure.

OBJECTIVE: To assess the effect of World Trade Center (WTC) exposure on cardiovascular disease (CVD) in career firefighters. Methods: Firefighters from four US cities completed health questionnaires that provide information about demographics, CVD diagnoses, and CVD risk factors. Firefighters were also compared with respondents of the 2019 National Health Interview Survey. Results: Greater WTC exposure was positively associated with combined coronary artery disease, myocardial infarction, and angina (termed "CAD") when comparing WTC-exposed with non-WTC-exposed firefighters. Compared with the National Health Interview Survey population, firefighters had lower odds of CAD and stroke. Conclusions: An occupationally appropriate comparison is important to mitigate potential bias from the healthy worker effect. While the risk of CVD in WTC-exposed and non-WTC-exposed firefighters was significantly lower than a general US population, we observed an exposure gradient where greater WTC exposure was associated with greater odds of CVD.

Correction: Colbeth et al. Mortality among Fire Department of the City of New York Rescue and Recovery Workers Exposed to the World Trade Center Disaster, 2001-2017. Int. J. Environ. Res. Public Health 2020, 17, 6266.

The original publication [...].

Association of Lung Function Decline with All-Cause and Cancer-Cause Mortality after World Trade Center Dust Exposure.

Rationale: In numerous cohorts, lung function decline is associated with all-cause and cardiovascular-cause mortality, but the association between the decrease in forced expiratory volume in 1 second (FEV1) and cancer-cause mortality, particularly after occupational/environmental exposure(s), is unclear. Exposure to dust/smoke from the World Trade Center (WTC) disaster caused inflammation and lung injury in Fire Department of the City of New York rescue/recovery workers. In addition, prior research found that >10% of the cohort experienced greater than twice the age-related decrease in FEV1 (⩾64 ml/yr). Objectives: To evaluate the association of longitudinal lung function with all-cause and cancer-cause mortality after exposure to the WTC disaster. Methods: We conducted a prospective cohort study using longitudinal prebronchodilator FEV1 data for 12,264 WTC-exposed firefighters and emergency medical service providers. All-cause and cancer-cause mortality were ascertained using National Death Index data from September 12, 2001, through December 31, 2021. Joint longitudinal survival models evaluated the association of baseline FEV1 and change in FEV1 from baseline with all-cause and cancer-cause mortality adjusted for age, race/ethnicity, height, smoking, work assignment (firefighters vs. emergency medical service providers), and WTC exposure. Results: By December 31, 2021, 607 of the 12,264 individuals in the cohort (4.9%) had died (crude rate = 259.5 per 100,000 person-years), and 190 of 12,264 (1.5%) had died from cancer (crude rate = 81.2 per 100,000 person-years). Baseline FEV1 was ⩾80% predicted in 10,970 of the 12,264 (89.4%); final FEV1 was ⩾80% in 9,996 (81.5%). Lower FEV1 at baseline was associated with greater risk for all-cause mortality (hazard ratio [HR] per liter = 2.32; 95% confidence interval [95% CI] = 1.98-2.72) and cancer-cause mortality (HR per liter = 1.99; 95% CI = 1.49-2.66). Longitudinally, each 100-ml/yr decrease in FEV1 was associated with an 11% increase in all-cause mortality (HR = 1.11; 95% CI = 1.06-1.15) and a 7% increase in cancer-cause mortality (HR = 1.07; 95% CI = 1.00-1.15). Compared with FEV1 decrease <64 ml/yr, those with FEV1 decrease ⩾64 ml/yr had higher all-cause (HR = 2.91; 95% CI = 2.37-3.56) and cancer-cause mortality (HR = 2.68; 95% CI = 1.90-3.79). Conclusions: Baseline FEV1 and longitudinal FEV1 decrease are associated with increased risk of all-cause and cancer-cause mortality in a previously healthy occupational cohort, the majority of whom had normal lung function, after intense exposure to dust/smoke. Further investigation is needed to define pathways by which lung function impacts mortality after an irritant exposure.

All-cause and cause-specific mortality in a cohort of WTC-exposed and non-WTC-exposed firefighters.

OBJECTIVE: To compare mortality rates in World Trade Center (WTC)-exposed Fire Department of the City of New York (FDNY) firefighters with rates in similarly healthy, non-WTC-exposed/non-FDNY firefighters, and compare mortality in each firefighter cohort with the general population. METHODS: 10 786 male WTC-exposed FDNY firefighters and 8813 male non-WTC-exposed firefighters from other urban fire departments who were employed on 11 September 2001 were included in the analyses. Only WTC-exposed firefighters received health monitoring via the WTC Health Programme (WTCHP). Follow-up began 11 September 2001 and ended at the earlier of death date or 31 December 2016. Death data were obtained from the National Death Index and demographics from the fire departments. We estimated standardised mortality ratios (SMRs) in each firefighter cohort versus US males using demographic-specific US mortality rates. Poisson regression models estimated relative rates (RRs) of all-cause and cause-specific mortality in WTC-exposed versus non-WTC-exposed firefighters, controlling for age and race. RESULTS: Between 11 September 2001 and 31 December 2016, there were 261 deaths among WTC-exposed firefighters and 605 among non-WTC-exposed. Both cohorts had reduced all-cause mortality compared with US males (SMR (95% CI)=0.30 (0.26 to 0.34) and 0.60 (0.55 to 0.65) in WTC-exposed and non-WTC-exposed, respectively). WTC-exposed firefighters also had lower rates of all-cause mortality (RR=0.54, 95% CI=0.49 to 0.59) and cancer-specific, cardiovascular-specific and respiratory disease-specific mortality compared with non-WTC-exposed firefighters. CONCLUSION: Both firefighter cohorts had lower than expected all-cause mortality. Fifteen years post 11 September 2001, mortality was lower in WTC-exposed versus non-WTC-exposed firefighters. Lower mortality in the WTC-exposed suggests not just a healthy worker effect, but additional factors such as greater access to free health monitoring and treatment that they receive via the WTCHP.

Comparing self-reported obstructive airway disease in firefighters with and without World Trade Center exposure.

BACKGROUND: The degree to which routine, non-World Trade Center (WTC) firefighting exposures contribute to the WTC exposure-obstructive airway disease (OAD) relationship is unknown. Our objective was to compare the frequency of self-reported OAD diagnoses in WTC-exposed firefighters from the Fire Department of the City of New York (FDNY) compared with non-WTC-exposed firefighters from other cities and the general population. METHODS: A total of 9792 WTC-exposed male FDNY firefighters and 3138 non-WTC-exposed male firefighters from Chicago, Philadelphia, and San Francisco who were actively employed on 9/11/01 and completed a health questionnaire were included. Logistic regression estimated odds ratios of self-reported asthma and COPD diagnoses in firefighters (WTC-exposed vs. non-WTC-exposed; all firefighters vs. general population), adjusting for age, race, smoking status, and last medical visit. RESULTS: WTC-exposed firefighters were, on average, younger on 9/11 (mean ± SD = 40.2 ± 7.4 vs. 44.1 ± 9.1) and less likely to report ever-smoking (32.9% vs. 41.8%) than non-WTC-exposed firefighters. Odds of any OAD and asthma were 4.5 and 6.3 times greater, respectively, in WTC-exposed versus non-WTC-exposed. Odds of COPD were also greater in WTC-exposed versus non-WTC-exposed, particularly among never-smokers. Compared with the general population, WTC-exposed firefighters had greater odds of both asthma and COPD, while the nonexposed had lower odds of asthma and greater odds of COPD. CONCLUSIONS: Odds ratios for OAD diagnoses were greater in WTC-exposed firefighters versus both non-WTC-exposed and the general population after adjusting for covariates. While asthma and other OADs are known occupational hazards of firefighting, WTC exposure significantly compounded these adverse respiratory effects.

A 15-year follow-up study of mortality in a pooled cohort of World Trade Center rescue and recovery workers.

INTRODUCTION: Hazardous exposures from the World Trade Center (WTC) terrorist attacks have been linked to increased incidence of adverse health conditions, often associated with increased mortality. We assessed mortality in a pooled cohort of WTC rescue/recovery workers over 15 years of follow-up. MATERIALS AND METHODS: We analyzed mortality through 2016 in a pooled and deduplicated cohort of WTC rescue/recovery workers from three WTC-exposed cohorts (N = 60,631): the Fire Department of the City of New York (FDNY); the WTC Health Registry (WTCHR); and the General Responder Cohort (GRC). Standardized mortality ratios (SMRs) were estimated to assess mortality vs. the US and NY state populations. Multivariable Cox proportional hazards models were used to examine associations of WTC exposures (date of first arrival, working on the WTC debris pile) with mortality risk. RESULTS: There were 1912 deaths over 697,943.33 person-years of follow-up. The SMR for all-cause mortality was significantly lower-than-expected, both when using US (SMR 0.43, 95% confidence interval [CI] 0.42-0.45) and NYS (SMR 0.51, 95% CI 0.49-0.53) as reference populations. SMRs were not elevated for any of the 28 major causes of death. Arriving at the WTC site on 9/11-9/17/2001 vs. 9/18/2001-6/30/2002 was associated with 30-50% higher risk of all-cause, heart disease and smoking-related mortality in non-FDNY/non-GRC members. Conversely, arriving on 9/11/2001 vs. 9/18/2001-6/30/2002 was associated with 40% lower all-cause and smoking-related mortality risk in FDNY members. Working on vs. off the WTC pile was associated with an increased risk of all-cause mortality in non-FDNY/non-GRC members (adjusted hazard ratio [aHR] 1.25, 95% CI 1.04-1.50), and cancer-specific mortality in GRC members (aHR 1.39, 95% CI 1.05-1.84), but lower mortality risks were found in FDNY members. CONCLUSIONS: We did not observe excess mortality among WTC rescue/recovery workers compared with general populations. However, significantly increased mortality risks among some sub-groups with high WTC exposure warrant further investigation.

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.

Association Between Socioeconomic and Insurance Status and Delayed Diagnosis of Gastrointestinal Cancers.

INTRODUCTION: Association between socioeconomic status (SES) and stage at diagnosis in gastrointestinal (GI) cancers is poorly described. Relationship between low SES and stage at diagnosis as well as the mediating role of insurance status (IS) was examined. METHODS: The Surveillance, Epidemiology, and End Results database was queried for esophageal, gastric, liver, biliary, pancreatic, colon, and rectal cancers diagnosed in 2012-2016. Relationship between census-tract SES index quintiles and late diagnosis (distant disease at diagnosis) was examined. Uni and multivariable logistic regressions were performed. Mediation analyses were conducted to determine the degree to which IS (private/Medicare versus Medicaid/uninsured) mediates the relationship between SES and late diagnosis of cancer. RESULTS: Analysis included 236,713 adult patients from 18 Surveillance, Epidemiology, and End Results areas. In univariable analysis, lowest SES quintile was significantly associated with late diagnosis for all cancers except gastric and biliary cancers. In multivariable analysis controlling for age, gender, marital status and race, this association remained significant for liver (odds ratio (OR) 1.41 [95% confidence interval (CI) 1.25-1.58]), pancreatic (OR 1.13 [95% CI 1.06-1.21]), and rectal (OR 1.31 [95% CI 1.20-1.42]) cancers. Further controlling for IS showed the largest effect size reduction for rectal cancer (OR 1.18 [95% CI 1.09-1.29]), with IS mediating 36.5% (P < 0.0001) of SES effect. CONCLUSIONS: Low SES is an independent risk factor for late diagnosis in liver, pancreas, and rectal cancers. Insurance is not a critical mediator of difference by SES for most GI cancers, with the exception of rectal cancer. Further research is needed to understand factors beyond IS that can account for SES differences in late diagnosis for GI cancers. Insurance related differences for rectal cancer deserves further attention.

Relationship between low serum immunoglobulin E levels and malignancies in 9/11 World Trade Center responders.

BACKGROUND: Individuals with very low immunoglobulin E (IgE) levels have a high risk of developing malignancy. Previous studies have revealed that World Trade Center (WTC) responders exposed to carcinogens have an elevated risk of some cancers. OBJECTIVE: To evaluate the association between low-serum IgE levels and cancer development in WTC-exposed responders. METHODS: IgE levels were measured in 1851 WTC responders after September 11, 2001. This is the first pilot study in humans comparing the odds of developing cancer in this high-risk population, between the "low-IgE" (IgE in the lowest third percentile) vs "non-low-IgE" participants. RESULTS: A significantly higher proportion of hematologic malignancies was found in low-IgE (4/55, 7.3%) compared with non-low-IgE (26/1796, 1.5%, P < .01) responders. The proportion of solid tumors were similar in both groups (5.5% vs 11.4%, P > .05). After adjustment for relevant confounders (race, sex, age at blood draw, WTC arrival time, smoking status), the low-IgE participants had 7.81 times greater odds (95% confidence interval, 1.77-29.35) of developing hematologic cancer when compared with non-low-IgE participants. The hematologic cancers found in this cohort were leukemia (n = 1), multiple myeloma (n = 1), and lymphoma (n = 2). No statistical significance was found when estimating the odds ratio for solid tumors in relation to IgE levels. CONCLUSION: WTC responders with low serum IgE levels had the highest odds of developing hematologic malignancies. This hypothesis-generating study suggests that low serum IgE levels might be associated with the development of specific malignancies in at-risk individuals exposed to carcinogens. Larger, multicenter studies with adequate follow-up of individuals with different IgE levels are needed to better evaluate this relationship.

Application of predictive models in boosting power of Alzheimer's disease clinical trials: A post hoc analysis of phase 3 solanezumab trials.

Background: The ideal participants for Alzheimer's disease (AD) clinical trials would show cognitive decline in the absence of treatment (i.e., placebo arm) and would also respond to the therapeutic intervention. Objective: To investigate if predictive models can be an effective tool for identifying and excluding people unlikely to show cognitive decline as an enrichment strategy in AD trials. Method: We used data from the placebo arms of two phase 3, double-blind trials, EXPEDITION and EXPEDITION2. Patients had 18 months of follow-up. Based on the longitudinal data from the placebo arm, we classified participants into two groups: one showed cognitive decline (any negative slope) and the other showed no cognitive decline (slope is zero or positive) on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-cog). We used baseline data for EXPEDITION to train regression-based classifiers and machine learning classifiers to estimate probability of cognitive decline. Models were applied to EXPEDITION2 data to assess predicted performance in an independent sample. Features used in predictive models included baseline demographics, apolipoprotein E ε4 genotype, neuropsychological scores, functional scores, and volumetric magnetic resonance imaging. Result: In EXPEDITION, 46.3% of placebo-treated patients showed no cognitive decline and the proportion was similar in EXPEDITION2 (45.6%). Models had high sensitivity and modest specificity in both the training (EXPEDITION) and replication samples (EXPEDITION2) for detecting the stable group. Positive predictive value of models was higher than the base prevalence of cognitive decline, and negative predictive value of models were higher than the base rate of participants who had stable cognition. Conclusion: Excluding persons with AD unlikely to decline from the active and placebo arms of clinical trials using predictive models may boost the power of AD trials through selective inclusion of participants expected to decline.

Cancer risk among World Trade Center rescue and recovery workers: A review.

Twenty years after the September 11th, 2001 terrorist attacks, the association between exposures present at the World Trade Center (WTC) site and the risk of several specific types of cancer has been reported among rescue and recovery workers. The authors' objective was to conduct an updated review of these data. Most studies have found elevated rates of both prostate and thyroid cancers compared with rates in the general population, and some have reported statistically significant differences for the rates of all cancers as well. Studies including a larger combined cohort of WTC-exposed rescue and recovery workers from 3 main cohorts have since replicated findings for these cancers, with additional years of follow-up. Among this combined cohort, although a lower-than-expected standardized incidence ratio for all cancers was observed, WTC exposure was also related to an increased risk of cutaneous melanoma and tonsil cancer. Importantly, another study found that WTC-exposed rescue and recovery workers who are enrolled in the federally funded medical monitoring and treatment program experienced improved survival post-cancer diagnosis compared with New York state patients with cancer. On the basis of these combined cohort studies, the full effect of WTC exposure on cancer risk is becoming clearer. Consequently, the authors believe that surveillance of those with WTC exposure should be continued, and in-depth analysis of epidemiologic, molecular, and clinical aspects of specific cancers in these workers should be pursued.

Temporal Aspects of the Association between Exposure to the World Trade Center Disaster and Risk of Cutaneous Melanoma.

Rescue/recovery workers who responded to the World Trade Center (WTC) attacks were exposed to known/suspected carcinogens. Studies have identified a trend toward an elevated risk of cutaneous melanoma in this population; however, few found significant increases. Furthermore, temporal aspects of the association have not been investigated. A total of 44,540 non-Hispanic White workers from the WTC Combined Rescue/Recovery Cohort were studied between March 12, 2002 and December 31, 2015. Cancer data were obtained through linkages with 13 state registries. Poisson regression was used to estimate hazard ratios and 95% confidence intervals using the New York State population as the reference; change points in hazard ratios were estimated using profile likelihood. We observed 247 incident cases of melanoma. No increase in incidence was detected during 2002-2004. From 2005 to 2015, the hazard ratio was 1.34 (95% confidence interval = 1.18-1.52). A dose‒response relationship was observed by arrival time at the WTC site. Risk was elevated just over 3 years after the attacks. Whereas WTC-related exposures to UVR or other agents might have contributed to this result, exposures other than those at the WTC site, enhanced medical surveillance, and lack of a control group with a similar proportion of rescue/recovery workers cannot be discounted. Our results support continued study of this population for melanoma.

Cognitive impairment and World Trade Centre-related exposures.

On 11 September 2001 the World Trade Center (WTC) in New York was attacked by terrorists, causing the collapse of multiple buildings including the iconic 110-story 'Twin Towers'. Thousands of people died that day from the collapse of the buildings, fires, falling from the buildings, falling debris, or other related accidents. Survivors of the attacks, those who worked in search and rescue during and after the buildings collapsed, and those working in recovery and clean-up operations were exposed to severe psychological stressors. Concurrently, these 'WTC-affected' individuals breathed and ingested a mixture of organic and particulate neurotoxins and pro-inflammogens generated as a result of the attack and building collapse. Twenty years later, researchers have documented neurocognitive and motor dysfunctions that resemble the typical features of neurodegenerative disease in some WTC responders at midlife. Cortical atrophy, which usually manifests later in life, has also been observed in this population. Evidence indicates that neurocognitive symptoms and corresponding brain atrophy are associated with both physical exposures at the WTC and chronic post-traumatic stress disorder, including regularly re-experiencing traumatic memories of the events while awake or during sleep. Despite these findings, little is understood about the long-term effects of these physical and mental exposures on the brain health of WTC-affected individuals, and the potential for neurocognitive disorders. Here, we review the existing evidence concerning neurological outcomes in WTC-affected individuals, with the aim of contextualizing this research for policymakers, researchers and clinicians and educating WTC-affected individuals and their friends and families. We conclude by providing a rationale and recommendations for monitoring the neurological health of WTC-affected individuals.

Cancer Incidence in World Trade Center Rescue and Recovery Workers: 14 Years of Follow-Up.

BACKGROUND: Statistically significantly increased cancer incidence has been reported from 3 cohorts of World Trade Center (WTC) disaster rescue and recovery workers. We pooled data across these cohorts to address ongoing public concerns regarding cancer risk 14 years after WTC exposure. METHODS: From a combined deduplicated cohort of 69 102 WTC rescue and recovery workers, a sample of 57 402 workers enrolled before 2009 and followed through 2015 was studied. Invasive cancers diagnosed in 2002-2015 were identified from 13 state cancer registries. Standardized incidence ratios (SIRs) were used to assess cancer incidence. Adjusted hazard ratios (aHRs) were estimated from Cox regression to examine associations between WTC exposures and cancer risk. RESULTS: Of the 3611 incident cancers identified, 3236 were reported as first-time primary (FP) cancers, with an accumulated 649 724 and 624 620 person-years of follow-up, respectively. Incidence for combined FP cancers was below expectation (SIR = 0.96, 95% confidence interval [CI] = 0.93 to 0.99). Statistically significantly elevated SIRs were observed for melanoma-skin (SIR = 1.43, 95% CI = 1.24 to 1.64), prostate (SIR = 1.19, 95% CI = 1.11 to 1.26), thyroid (SIR = 1.81, 95% CI = 1.57 to 2.09), and tonsil (SIR = 1.40, 95% CI = 1.00 to 1.91) cancer. Those arriving on September 11 had statistically significantly higher aHRs than those arriving after September 17, 2001, for prostate (aHR = 1.61, 95% CI = 1.33 to 1.95) and thyroid (aHR = 1.77, 95% CI = 1.11 to 2.81) cancers, with a statistically significant exposure-response trend for both. CONCLUSIONS: In the largest cohort of 9/11 rescue and recovery workers ever studied, overall cancer incidence was lower than expected, and intensity of WTC exposure was associated with increased risk for specific cancer sites, demonstrating the value of long-term follow-up studies after environmental disasters.

Education, Occupational Complexity, and Incident Dementia: A COSMIC Collaborative Cohort Study.

BACKGROUND: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. OBJECTIVE: This project aimed to examine the unique contributions of education and occupational complexity to incident dementia, and to assess the mediating effects of occupational complexity on the association between education and dementia across diverse cohorts. METHOD: We used data from 10,195 participants (median baseline age = 74.1, range = 58∼103), representing 9 international datasets from 6 countries over 4 continents. Using a coordinated analysis approach, the accelerated failure time model was applied to each dataset, followed by meta-analysis. In addition, causal mediation analyses were performed. RESULT: The meta-analytic results indicated that both education and occupational complexity were independently associated with increased dementia-free survival time, with 28%of the effect of education mediated by occupational complexity. There was evidence of threshold effects for education, with increased dementia-free survival time associated with 'high school completion' or 'above high school' compared to 'middle school completion or below'. CONCLUSION: Using datasets from a wide range of geographical regions, we found that both early life education and adulthood occupational complexity were independently predictive of dementia. Education and occupational experiences occur during early life and adulthood respectively, and dementia prevention efforts could thus be made at different stages of the life course.