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.

A protocol for the prospective study of urinary cadmium with risk of fracture, bone loss, and muscle loss.

Cadmium (Cd) is a heavy metal and natural element found in soil and crops with increasing concentrations linked to phosphate fertilizers and sewage sludge applied to crop lands. A large fraction of older US men and woman have documented Cd exposure. Cd exposure has proven health concerns such as risk of lung cancer from inhalation and impaired renal function; however, growing evidence suggests it also influences bone and muscle health. Given that low levels of Cd could affect bone and muscle, we have designed prospective studies using the two largest and most detailed US studies of bone health in older men and women: the Osteoporotic Fractures in Men Study and the Study of Osteoporotic Fractures. We are investigating the association of urinary cadmium (U-Cd), as a surrogate for long-term Cd exposure, with bone and muscle health. Building off suggestive evidence from mechanistic and cross-sectional studies, this will be the first well-powered prospective study of incident fracture outcomes, bone loss, and muscle loss in relation to U-Cd, an established biomarker of long-term Cd exposure. The following is a proposed protocol for the intended study; if successful, the proposed studies could be influential in directing future US policy to decrease Cd exposure in the US population similar to recent policies adopted by the European Union to limit Cd in fertilizers.

Radon Exposure, Clonal Hematopoiesis, and Stroke Susceptibility in the Women's Health Initiative.

BACKGROUND AND OBJECTIVES: Studies suggest that clonal hematopoiesis of indeterminate potential (CHIP) may increase risk of hematologic malignancy and cardiovascular disease, including stroke. However, few studies have investigated plausible environmental risk factors for CHIP such as radon, despite the climate-related increases in and documented infrequency of testing for this common indoor air pollutant.The purpose of this study was to estimate the risk of CHIP related to radon, an established environmental mutagen. METHODS: We linked geocoded addresses of 10,799 Women's Health Initiative Trans-Omics for Precision Medicine (WHI TOPMed) participants to US Environmental Protection Agency-predicted, county-level, indoor average screening radon concentrations, categorized as follows: Zone 1 (>4 pCi/L), Zone 2 (2-4 pCi/L), and Zone 3 (<2 pCi/L). We defined CHIP as the presence of one or more leukemogenic driver mutations with variant allele frequency >0.02. We identified prevalent and incident ischemic and hemorrhagic strokes; subtyped ischemic stroke using Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria; and then estimated radon-related risk of CHIP as an odds ratio (OR) and 95% CI using multivariable-adjusted, design-weighted logistic regression stratified by age, race/ethnicity, smoking status, and stroke type/subtype. RESULTS: The percentages of participants with CHIP in Zones 1, 2, and 3 were 9.0%, 8.4%, and 7.7%, respectively (ptrend = 0.06). Among participants with ischemic stroke, Zones 2 and 1 were associated with higher estimated risks of CHIP relative to Zone 3: 1.39 (1.15-1.68) and 1.46 (1.15-1.87), but not among participants with hemorrhagic stroke: 0.98 (0.68-1.40) and 1.03 (0.70-1.52), or without stroke: 1.04 (0.74-1.46) and 0.95 (0.63-1.42), respectively (pinteraction = 0.03). Corresponding estimates were particularly high among TOAST-subtyped cardioembolism: 1.78 (1.30-2.47) and 1.88 (1.31-2.72), or other ischemic etiologies: 1.37 (1.06-1.78) and 1.50 (1.11-2.04), but not small vessel occlusion: 1.05 (0.74-1.49) and 1.00 (0.68-1.47), respectively (pinteraction = 0.10). Observed patterns of association among strata were insensitive to attrition weighting, ancestry adjustment, prevalent stroke exclusion, separate analysis of DNMT3A driver mutations, and substitution with 3 alternative estimates of radon exposure. DISCUSSION: The robust elevation of radon-related risk of CHIP among postmenopausal women who develop incident cardioembolic stroke is consistent with a potential role of somatic genomic mutation in this societally burdensome form of cerebrovascular disease, although the mechanism has yet to be confirmed.

Monitoring of over-the-counter (OTC) and COVID-19 treatment drugs complement wastewater surveillance of SARS-CoV-2.

BACKGROUND: The application of wastewater-based epidemiology to track the outbreak and prevalence of coronavirus disease (COVID-19) in communities has been tested and validated by several researchers across the globe. However, the RNA-based surveillance has its inherent limitations and uncertainties. OBJECTIVE: This study aims to complement the ongoing wastewater surveillance efforts by analyzing other chemical biomarkers in wastewater to help assess community response (hospitalization and treatment) during the pandemic (2020-2021). METHODS: Wastewater samples (n = 183) were collected from the largest wastewater treatment facility in Suffolk County, NY, USA and analyzed for COVID-19 treatment drugs (remdesivir, chloroquine, and hydroxychloroquine (HCQ)) and their human metabolites. We additionally monitored 26 pharmaceuticals including common over-the-counter (OTC) drugs. Lastly, we developed a Bayesian model that uses viral RNA, COVID-19 treatment drugs, and pharmaceuticals data to predict the confirmed COVID-19 cases within the catchment area. RESULTS: The viral RNA levels in wastewater tracked the actual COVID-19 case numbers well as expected. COVID-19 treatment drugs were detected with varying frequency (9-100%) partly due to their instability in wastewater. We observed a significant correlation (R = 0.30, p < 0.01) between the SARS-CoV-2 genes and desethylhydroxychloroquine (DHCQ, metabolite of HCQ). Remdesivir levels peaked immediately after the Emergency Use Authorization approved by the FDA. Although, 13 out of 26 pharmaceuticals assessed were consistently detected (DF = 100%, n = 111), only acetaminophen was significantly correlated with viral loads, especially when the Omicron variant was dominant. The Bayesian models were capable of reproducing the temporal trend of the confirmed cases. IMPACT: In this study, for the first time, we measured COVID-19 treatment and pharmaceutical drugs and their metabolites in wastewater to complement ongoing COVID-19 viral RNA surveillance efforts. Our results highlighted that, although the COVID-19 treatment drugs were not very stable in wastewater, their detection matched with usage trends in the community. Acetaminophen, an OTC drug, was significantly correlated with viral loads and confirmed cases, especially when the Omicron variant was dominant. A Bayesian model was developed which could predict COVID-19 cases more accurately when incorporating other drugs data along with viral RNA levels in wastewater.

In vitro and in vivo approaches to assess atherosclerosis following exposure to low-dose mixtures of arsenic and cadmium.

Worldwide, millions of people are co-exposed to arsenic and cadmium. Environmental exposure to both metals is linked with a higher risk of atherosclerosis. While studies have characterized the pro-atherosclerotic effects of arsenic and cadmium as single agents, little is known about the potential effects of metal mixtures, particularly at low doses. Here, we used a combination of in vitro and in vivo models to assess the effects of low-dose metals individually and as mixtures on early events and plaque development associated with atherosclerosis. In vitro, we investigated early pro-atherogenic changes in macrophages and endothelial cells with metal treatments. The combined cytotoxic effects of both metals at low concentrations were dose interactive, specifically, synergistic in macrophages, but antagonistic in endothelial cells. Despite this differential behavior across cell types, the mixtures did not initiate early pro-atherogenic events: neither reactive oxygen species generation in macrophages nor adhesion molecule expression on endothelial cells. In vivo, we utilized the well-characterized hyperlipidemic apolipoprotein E knock-out (ApoE-/-) mouse model. Previously, we have shown that low concentrations of arsenic (down to 10 ppb) enhance atherosclerosis in ApoE-/- mice. This model has also been used with cadmium to demonstrate pro-atherogenic effects, although at concentrations above human-relevant exposures. In both sexes, there are some small increases in atherosclerotic lesion size, but very few changes in plaque constituents in the ApoE-/- mouse model. Together, these results suggests that low-dose metal mixtures are not significantly more pro-atherogenic than either metal alone.

Urine antimony and risk of cardiovascular disease - A prospective case-cohort study in Danish Non-Smokers.

BACKGROUND: Limited evidence suggests that antimony induces vascular inflammation and oxidative stress and may play a role in cardiovascular disease (CVD) risk. However, few studies have examined whether environmental antimony from sources other than tobacco smoking is related with CVD risk. The general population may be exposed through air, drinking water, and food that contains antimony from natural and anthropogenic sources, such as mining, coal combustion, and manufacturing. OBJECTIVES: To examine the association of urine antimony with incident acute myocardial infarction (AMI), heart failure, and stroke among people who never smoked tobacco. METHODS: Between 1993 and 1997, the Danish Diet, Cancer and Health (DCH) cohort enrolled participants (ages 50-64 years), including n = 19,394 participants who reported never smoking at baseline. Among these never smokers, we identified incident cases of AMI (N = 809), heart failure (N = 958), and stroke (N = 534) using the Danish National Patient Registry. We also randomly selected a subcohort of 600 men and 600 women. We quantified urine antimony concentrations in samples provided at enrollment. We used modified Cox proportional hazards models to estimate adjusted hazard ratios (HR) for each incident CVD outcome in relation to urine antimony, statistically adjusted for creatinine. We used a separate prospective cohort, the San Luis Valley Diabetes Study (SLVDS), to replicate these results. RESULTS: In the DCH cohort, urine antimony concentrations were positively associated with rates of AMI and heart failure (HR = 1.52; 95%CI = 1.12, 2.08 and HR = 1.58; 95% CI = 1.15, 2.18, respectively, comparing participants in the highest (>0.09 µg/L) with the lowest quartile (<0.02 µg/L) of antimony). In the SLVDS cohort, urinary antimony was positively associated with AMI, but not heart failure. DISCUSSION: Among this sample of Danish people who never smoked, we found that low levels of urine antimony are associated with incident CVD. These results were partially confirmed in a smaller US cohort.

Nutrition Literacy: What Are Young Adults With Type-1 Diabetes Missing?

INTRODUCTION: This study evaluated the nutrition literacy and perceived emotional burden of disease in young adults with type-1 diabetes. All participants are current or past members of the non-profit organization The Diabetes Link, formally known as the College Diabetes Network. The Diabetes Link is a 501(c)(3) nonprofit organization working to connect and support young adults with type-1 diabetes through the transitional periods of their lives, most commonly the transition from high school to college. Previous research shows that there is a significant uptick in glycated hemoglobin (HbA1c) levels in people with type-1 diabetes between the ages of 18 and 24, a period associated with many transitional events. While there are numerous hypothesized reasons why HbA1c levels spike during these ages, the lack of nutritional knowledge is frequently highlighted as a root cause of this increase. METHODS: Participants were asked to complete a 40-question survey via Google Forms (Google LLC, Mountain View, California, United States) that contained questions pertaining to their treatment, dietary habits, confidence in healthcare professionals to provide nutrition advice, and overall feelings toward their diagnosis of type-1 diabetes. The survey also included four questions aimed at evaluating the participants' carbohydrate-counting skills to determine a basis of their nutritional knowledge. A binary logistic regression was performed using IBM SPSS Statistics for Windows, Version 27 (Released 2020; IBM Corp., Armonk, New York, United States) to assess the influences of the burden and carbohydrate-counting knowledge on the participants' diabetes care, eating habits, and emotional outlook on nutrition. RESULTS: Data from this study show that the participants who scored high on the carbohydrate-counting quiz were 2.389 times more likely to avoid eating because of an out-of-range blood sugar level (p-value = 0.05), and the participants who reported higher levels of burden were 9.325 times more likely to avoid social gatherings because of food (p-value = 0.002).  Conclusion: Results from this study demonstrate that the emotional burden associated with eating and not nutrition knowledge could contribute to the previously listed spike in HbA1c levels.

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.

Depression and Anxiety on Twitter During the COVID-19 Stay-At-Home Period in 7 Major U.S. Cities.

Introduction: Although surveys are a well-established instrument to capture the population prevalence of mental health at a moment in time, public Twitter is a continuously available data source that can provide a broader window into population mental health. We characterized the relationship between COVID-19 case counts, stay-at-home orders because of COVID-19, and anxiety and depression in 7 major U.S. cities utilizing Twitter data. Methods: We collected 18 million Tweets from January to September 2019 (baseline) and 2020 from 7 U.S. cities with large populations and varied COVID-19 response protocols: Atlanta, Chicago, Houston, Los Angeles, Miami, New York, and Phoenix. We applied machine learning‒based language prediction models for depression and anxiety validated in previous work with Twitter data. As an alternative public big data source, we explored Google Trends data using search query frequencies. A qualitative evaluation of trends is presented. Results: Twitter depression and anxiety scores were consistently elevated above their 2019 baselines across all the 7 locations. Twitter depression scores increased during the early phase of the pandemic, with a peak in early summer and a subsequent decline in late summer. The pattern of depression trends was aligned with national COVID-19 case trends rather than with trends in individual states. Anxiety was consistently and steadily elevated throughout the pandemic. Google search trends data showed noisy and inconsistent results. Conclusions: Our study shows the feasibility of using Twitter to capture trends of depression and anxiety during the COVID-19 public health crisis and suggests that social media data can supplement survey data to monitor long-term mental health trends.

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.

Domestic violence calls for police service in five US cities during the COVID-19 pandemic of 2020.

BACKGROUND: When COVID-19 stay-at-home orders were instituted, there were concerns that isolation may lead to increases in domestic violence (DV). Reports of increased rates of DV during the stay-at-home period have been suggestive of this but inconsistent across different locations. We sought to complement the existing studies by characterizing changes in DV trends in US cities of Chicago, Los Angeles (LA), New York City (NYC), Philadelphia, and Phoenix using police call volume data from January 1st, 2018, through Dec 31st, 2020. METHODS: The stay-at-home orders were generally instituted for most US states in the second half of March 2020. We used the call volume for the pre-COVID-19 period (Jan. 2018 to Feb. 2020) to model a forecast against the stay-at-home order period (Mar. - May 2020) and the period after lifting the order (June - Dec. 2020) using the interrupted autoregressive integrated moving average (ARIMA) time series model. RESULTS: During the stay-at-home order, increases in mean DV calls relative to pre-COVID-19 were observed in Chicago (47.8%), Phoenix (18.4%), NYC (3.5%), and LA (3.4%), but a decrease in Philadelphia (-4.9%). After lifting the stay-at-home order, changes in mean calls relative to pre-COVID-19 remained elevated in Chicago, slightly elevated in Phoenix, and returned to baseline in NYC and LA. CONCLUSION: Results suggest that the stay-at-home orders may have contributed to an increase in DV calls in some cities (Phoenix, and to a smaller extent LA, NYC), but the increase seen in Chicago (and to some extent Phoenix) persisted beyond the stay-at-home order and therefore may not be attributable to the stay-at-home orders. Additional studies are needed to help explain why the association between stay-at-home orders and DV police call volume seems to only appear in some locations.

Antimony and sleep health outcomes: NHANES 2009-2016.

OBJECTIVES: Following an earlier National Health and Nutrition Examination Survey (NHANES) 2005-2008 analysis, we investigated the association between urine antimony and sleep health using more recent data, new measures of sleep health, and multiple measures of urine density adjustment in NHANES 2009-2016. DESIGN: A cross-sectional study. SETTING: United States, national population-based survey. MEASUREMENTS: Multinomial logistic regression (sleep duration) and a generalized linear model with log-binomial regression (OSA, daytime sleepiness, sleep problems) were used to analyze the association of urinary antimony with sleep health outcomes. Urine creatinine and osmolality were considered, combined with statistical adjustment and standardization to account for urine density. PARTICIPANTS: A total of 8133 adult participants over 20 years of age were used using NHANES 2009-2016. RESULTS: We did not observe associations between urine antimony and short sleep duration or sleep problems. We observed mixed results for long sleep duration; there was a negative association in NHANES 2015-2016 and no association in NHANES 2009-2014. For self-reported symptoms of OSA, which were only available in 2015-2016, we observed a positive association for upper quartile urine antimony compared with the first quartile (RR = 1.24; 95% CI: 1.03, 1.50) and a test for trend, P= .02. CONCLUSION: Urinary antimony was not consistently associated with short sleep duration, long sleep duration, or sleep problems, despite the findings from a relatively recent scientific article using earlier waves of NHANES. We observed a positive association between antimony and symptoms of OSA; this cross-sectional analysis requires confirmation.

Association of Global Cognitive Function With Psychological Distress and Adherence to Public Health Recommendations During the Coronavirus Disease 2019 Pandemic: The Women's Health Initiative.

BACKGROUND: The association of cognitive function with symptoms of psychological distress during the coronavirus disease 2019 (COVID-19) pandemic or adherence to COVID-19 protective health behaviors is not well-understood. METHODS: We examined 2 890 older women from the Women's Health Initiative cohort. Prepandemic (ie, within 12 months prior to pandemic onset) and peripandemic global cognitive function scores were assessed with the modified Telephone Interview for Cognitive Status (TICS-m). Anxiety, stress, and depressive symptom severity during the pandemic were assessed using validated questionnaires. We examined adherence to protective behaviors that included safe hygiene, social distancing, mask wearing, and staying home. Multivariable models were adjusted for age, race, ethnicity, education, region of residence, alcohol intake, and comorbidities. RESULTS: Every 5-point lower prepandemic TICS-m score was associated with 0.33-point mean higher (95% confidence interval [CI], 0.20, 0.45) perceived stress and 0.20-point mean higher (95% CI, 0.07, 0.32) depressive symptom severity during the pandemic. Higher depressive symptom severity, but not anxiety or perceived stress, was associated with a 0.69-point (95% CI, -1.13, -0.25) mean decline in TICS-m from the prepandemic to peripandemic period. Every 5-point lower peripandemic TICS-m score was associated with 12% lower odds ratio (OR, 0.88; 95% CI, 0.80, 0.97) of practicing safe hygiene. CONCLUSIONS: Among older women, we observed that: (a) lower prepandemic global cognitive function was associated with higher stress and depressive symptom severity during the pandemic; (b) higher depressive symptom severity during the pandemic was associated with cognitive decline; and (c) lower global cognitive function during the pandemic was associated with lower odds of practicing safe hygiene.

The Impact of the COVID-19 Pandemic on Older Women in the Women's Health Initiative.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic is a health crisis of which older adults are a high-risk group for severe illness and mortality. The objectives of this article are to describe the methods and responses to a COVID-19 survey administered by the Women's Health Initiative (WHI) to assess the impact of the pandemic on older women. METHODS: WHI is an ongoing prospective cohort study that recruited 161 808 postmenopausal women from 1993 to 1998. From June 2020 to October 2020, participants in active follow-up were surveyed by mail, phone, or online to assess health and well-being, living situations, lifestyle, health care, and self-reported COVID-19 testing, treatment, and preventive behaviors. RESULTS: Of 64 061 eligible participants, 49 695 (average age 83.6 years ± 5.6) completed the COVID-19 survey (response rate 77.6%). Many participants reported very good or good well-being (75.6%). Respondents reported being very concerned about the pandemic (51.1%; more common in urban compared to rural areas), with 6.9% reporting disruptions in living arrangements and 9.7% reporting changes in medication access. Participants (54.4%) reported physical activity levels were much less or somewhat less compared to levels before the pandemic, and this was more pronounced in urban areas versus rural areas (55.3% vs 44.4%). Participants engaged in preventive behaviors including wearing a face mask (93.2%). A total of 18.9% reported testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), among whom 3.5% (n = 311) reported testing positive. CONCLUSIONS: In this nationwide survey of older U.S. women, the COVID-19 pandemic was associated with impacts on health and well-being, living situations, lifestyle, health care access, and SARS-CoV-2 testing and preventive behaviors.

Urinary Cadmium and Incident Heart Failure: A Case-Cohort Analysis Among Never-Smokers in Denmark.

BACKGROUND: Epidemiologic studies suggest cadmium exposure is associated with cardiovascular disease risk, including heart failure. However, prior findings may be influenced by tobacco smoking, a dominant source of cadmium exposure and risk factor for heart failure. The present study leverages up to 20 years of follow-up in the Danish Diet, Cancer and Health cohort to examine the relationship between urinary cadmium and incident heart failure among people who never smoked. METHODS: Between 1993 and 1997, 19,394 never-smoking participants (ages 50-64 years) enrolled and provided a urine sample. From this sample, we randomly selected a subcohort of 600 men and 600 women and identified 958 incident heart failure cases occurring between baseline and 2015. Using a case-cohort approach, we estimated adjusted hazard ratios (aHR) for heart failure in Cox proportional hazards models with age as the time scale. RESULTS: Participants had relatively low concentrations of urinary cadmium, as expected for never smokers (median = 0.20; 25th, 75th = 0.13, 0.32 µg cadmium/g creatinine). In adjusted models, we found that higher urinary cadmium was associated with a higher rate of incident heart failure overall (aHR = 1.1 per interquartile range difference [95% CI = 1.0, 1.2). In sex-stratified analyses, the association seemed restricted to men (aHR = 1.5 [95% CI = 1.2, 1.9]). CONCLUSIONS: In this cohort of people who never smoked tobacco, environmental cadmium was positively associated with incident heart failure, especially among men.

Associations Between Changes in Loneliness and Social Connections, and Mental Health During the COVID-19 Pandemic: The Women's Health Initiative.

BACKGROUND: Older women have faced significant disruptions in social connections during the coronavirus disease 2019 pandemic. Whether loneliness increased or whether a change in loneliness from pre- to intrapandemic period was associated with mental health during the pandemic is unknown. METHODS: Older women (n = 27 479; mean age 83.2 [SD: 5.4] years) completed surveys in mid-2020, including questions about loneliness, living arrangements, changes in social connections, and mental health. Loneliness was also previously assessed in 2014-2016. We examined whether loneliness changed from the pre- to intrapandemic period and explored factors associated with this change. In multivariable models, we investigated the association of changes in loneliness and social connections with mental health. RESULTS: Loneliness increased from pre- to intrapandemic levels. Factors associated with worsening loneliness included older age, experiencing stressful life events, bereavement, histories of vascular disease and depression, and social connection disruptions. Factors associated with a decrease in loneliness included identifying as Black, engaging in more frequent physical activity, being optimistic, and having a higher purpose in life. A 3-point increase in loneliness scores was associated with higher perceived stress, higher depressive, and higher anxiety symptoms. Social connection disruptions showed modest or no associations with mental health. CONCLUSIONS: Loneliness increased during the pandemic in older women and was associated with higher stress, depressive, and anxiety symptoms. Our findings point to opportunities for interventions targeting lifestyle behaviors, well-being, disrupted social connections, and paying closer attention to those with specific medical and mental health histories that may reduce loneliness and improve mental health.

A wind speed threshold for increased outdoor transmission of coronavirus: an ecological study.

BACKGROUND: To examine whether outdoor transmission may contribute to the COVID-19 epidemic, we hypothesized that slower outdoor wind speed is associated with increased risk of transmission when individuals socialize outside. METHODS: Daily COVID-19 incidence reported in Suffolk County, NY, between March 16th and December 31st, 2020, was the outcome. Average wind speed and maximal daily temperature were collated by the National Oceanic and Atmospheric Administration. Negative binomial regression was used to model incidence rates while adjusting for susceptible population size. RESULTS: Cases were very high in the initial wave but diminished once lockdown procedures were enacted. Most days between May 1st, 2020, and October 24th, 2020, had temperatures 16-28 °C and wind speed diminished slowly over the year and began to increase again in December 2020. Unadjusted and multivariable-adjusted analyses revealed that days with temperatures ranging between 16 and 28 °C where wind speed was < 8.85 km per hour (KPH) had increased COVID-19 incidence (aIRR = 1.45, 95% C.I. = [1.28-1.64], P < 0.001) as compared to days with average wind speed ≥ 8.85 KPH. CONCLUSION: Throughout the U.S. epidemic, the role of outdoor shared spaces such as parks and beaches has been a topic of considerable interest. This study suggests that outdoor transmission of COVID-19 may occur by noting that the risk of transmission of COVID-19 in the summer was higher on days with low wind speed. Outdoor use of increased physical distance between individuals, improved air circulation, and use of masks may be helpful in some outdoor environments where airflow is limited.

Relationship between Urine Creatinine and Urine Osmolality in Spot Samples among Men and Women in the Danish Diet Cancer and Health Cohort.

Assays of urine biomarkers often use urine creatinine to account for urinary dilution, even though creatinine levels are influenced by underlying physiology and muscle catabolism. Urine osmolality-a measure of dissolved particles including ions, glucose, and urea-is thought to provide a more robust marker of urinary dilution but is seldom measured. The relationship between urine osmolality and creatinine is not well understood. We calculated correlation coefficients between urine creatinine and osmolality among 1375 members of a subcohort of the Danish Diet, Cancer, and Health Cohort, and within different subgroups. We used linear regression to relate creatinine with osmolality, and a lasso selection procedure to identify other variables that explain remaining variability in osmolality. Spearman correlation between urine creatinine and osmolality was strong overall (ρ = 0.90; 95% CI: 0.89-0.91) and in most subgroups. Linear regression showed that urine creatinine explained 60% of the variability in urine osmolality, with another 9% explained by urine thallium (Tl), cesium (Cs), and strontium (Sr). Urinary creatinine and osmolality are strongly correlated, although urine Tl, Cs, and Sr might help supplement urine creatinine for purposes of urine dilution adjustment when osmolality is not available.

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.

Urinary cadmium and stroke - a case-cohort study in Danish never-smokers.

BACKGROUND: and Purpose: Cadmium has been associated with risk of cardiovascular events, including stroke. Human cadmium exposure occurs primarily through diet and tobacco smoke. Recent cohort studies have found an association with stroke, but residual confounding from smoking, could not be ruled out. We therefore conducted a case-cohort study to evaluate whether cadmium is associated with stroke in never-smokers. METHODS: The Danish Diet Cancer and Health cohort consists of Danes 50-64 years old, recruited in 1993-1997. From never-smoking cohort members without previous cancer or stroke we sampled a sub-cohort of 1200 persons. We also identified all (n = 534) cases in the cohort with a validated stroke diagnosis between baseline and 2009. We quantified cadmium and creatinine concentrations from baseline urine samples and used cadmium per creatinine as our main exposure metric. We used Cox proportional hazards models to estimate hazard ratios (HRs) with age as time scale and adjusting for BMI, education and urinary cotinine with and without stratification by sex. RESULTS: The median urinary cadmium concentration was 0.21 µg cadmium/g creatinine in cases and 0.19 µg/g in the sub-cohort. The majority (83%) of stroke cases were diagnosed with ischemic stroke. The HR for stroke in the highest quartile of exposure (median 0.44 µg/g creatinine) was 1.11 (95% CI: 0.79-1.54) compared with the lowest quartile (median 0.10 µg/g creatinine). The HR per inter quartile range (IQR, 0.19 µg/g creatinine) was 1.02 (95% CI: 0.92-1.12). Among men, the HR per IQR higher levels of cadmium (0.16 µg/g creatinine) was 1.18 (95% CI: 0.92-1.52), and 1.00 (95% CI: 0.89-1.12) among women. Adjusting for creatinine or using osmolality instead of creatinine standardization generally attenuated observed relationships. CONCLUSIONS: Our results do not support that low levels of cadmium exposure among never-smokers are strongly associated with risk of stroke, although results varied somewhat by sex and method of accounting for urinary dilution.