Association between Fine Particulate Matter Exposure and Cerebrospinal Fluid Biomarkers of Alzheimer's Disease among a Cognitively Healthy Population-Based Cohort.

BACKGROUND: Epidemiological evidence suggests air pollution adversely affects cognition and increases the risk of Alzheimer's disease (AD), but little is known about the biological effects of fine particulate matter (PM2.5, particulate matter with aerodynamic diameter ≤2.5µm) on early predictors of future disease risk. OBJECTIVES: We investigated the association between 1-, 3-, and 5-y exposure to ambient and traffic-related PM2.5 and cerebrospinal fluid (CSF) biomarkers of AD. METHODS: We conducted a cross-sectional analysis using data from 1,113 cognitively healthy adults (45-75 y of age) from the Emory Healthy Brain Study in Georgia in the United States. CSF biomarker concentrations of Aß42, tTau, and pTau, were collected at enrollment (2016-2020) and analyzed with the Roche Elecsys system. Annual ambient and traffic-related residential PM2.5 concentrations were estimated at a 1-km and 250-m resolution, respectively, and computed for each participant's geocoded address, using three exposure time periods based on specimen collection date. Associations between PM2.5 and CSF biomarker concentrations, considering continuous and dichotomous (dichotomized at clinical cutoffs) outcomes, were estimated with multiple linear/logistic regression, respectively, controlling for potential confounders (age, gender, race, ethnicity, body mass index, and neighborhood socioeconomic status). RESULTS: Interquartile range (IQR; IQR=0.845) increases in 1-y [ß:-0.101; 95% confidence interval (CI): -0.18, -0.02] and 3-y (ß:-0.078; 95% CI: -0.15, -0.00) ambient PM2.5 exposures were negatively associated with Aß42 CSF concentrations. Associations between ambient PM2.5 and Aß42 were similar for 5-y estimates (ß:-0.076; 95% CI: -0.160, 0.005). Dichotomized CSF variables revealed similar associations between ambient PM2.5 and Aß42. Associations with traffic-related PM2.5 were similar but not significant. Associations between PM2.5 exposures and tTau, pTau tTau/Aß42, or pTau/Aß42 levels were mainly null. CONCLUSION: In our study, consistent trends were found between 1-y PM2.5 exposure and decreased CSF Aß42, which suggests an accumulation of amyloid plaques in the brain and an increased risk of developing AD. https://doi.org/10.1289/EHP13503.

Associations of pollen and cardiovascular disease morbidity in Atlanta during 1993-2018.

Background: Pollen exposure is associated with substantial respiratory morbidity, but its potential impact on cardiovascular disease (CVD) remains less understood. This study aimed to investigate the associations between daily levels of 13 pollen types and emergency department (ED) visits for eight CVD outcomes over a 26-year period in Atlanta, GA. Methods: We acquired pollen data from Atlanta Allergy & Asthma, a nationally certified pollen counting station, and ED visit data from individual hospitals and the Georgia Hospital Association. We performed time-series analyses using quasi-Poisson distributed lag models, with primary analyses assessing 3-day (lag 0-2 days) pollen levels. Models controlled for temporally varying covariates, including air pollutants. Results: During 1993-2018, there were 1,573,968 CVD ED visits. Most pairwise models of the 13 pollen types and eight CVD outcomes showed no association, with a few exceptions potentially due to chance. Conclusion: We found limited evidence of the impact of pollen on cardiovascular morbidity in Atlanta. Further study on pollen exposures in different climactic zones and exploration of pollen-pollution mixture effects is warranted.

Joint effects of air pollution and neighborhood socioeconomic status on cognitive decline - Mediation by depression, high cholesterol levels, and high blood pressure.

Air pollution and neighborhood socioeconomic status (N-SES) are associated with adverse cardiovascular health and neuropsychiatric functioning in older adults. This study examines the degree to which the joint effects of air pollution and N-SES on the cognitive decline are mediated by high cholesterol levels, high blood pressure (HBP), and depression. In the Emory Healthy Aging Study, 14,390 participants aged 50+ years from Metro Atlanta, GA, were assessed for subjective cognitive decline using the cognitive function instrument (CFI). Information on the prior diagnosis of high cholesterol, HBP, and depression was collected through the Health History Questionnaire. Participants' census tracts were assigned 3-year average concentrations of 12 air pollutants and 16 N-SES characteristics. We used the unsupervised clustering algorithm Self-Organizing Maps (SOM) to create 6 exposure clusters based on the joint distribution of air pollution and N-SES in each census tract. Linear regression analysis was used to estimate the effects of the SOM cluster indicator on CFI, adjusting for age, race/ethnicity, education, and neighborhood residential stability. The proportion of the association mediated by high cholesterol levels, HBP, and depression was calculated by comparing the total and direct effects of SOM clusters on CFI. Depression mediated up to 87 % of the association between SOM clusters and CFI. For example, participants living in the high N-SES and high air pollution cluster had CFI scores 0.05 (95 %-CI:0.01,0.09) points higher on average compared to those from the high N-SES and low air pollution cluster; after adjusting for depression, this association was attenuated to 0.01 (95 %-CI:-0.04,0.05). HBP mediated up to 8 % of the association between SOM clusters and CFI and high cholesterol up to 5 %. Air pollution and N-SES associated cognitive decline was partially mediated by depression. Only a small portion (<10 %) of the association was mediated by HBP and high cholesterol.

A scalar-on-quantile-function approach for estimating short-term health effects of environmental exposures.

Environmental epidemiologic studies routinely utilize aggregate health outcomes to estimate effects of short-term (eg, daily) exposures that are available at increasingly fine spatial resolutions. However, areal averages are typically used to derive population-level exposure, which cannot capture the spatial variation and individual heterogeneity in exposures that may occur within the spatial and temporal unit of interest (eg, within a day or ZIP code). We propose a general modeling approach to incorporate within-unit exposure heterogeneity in health analyses via exposure quantile functions. Furthermore, by viewing the exposure quantile function as a functional covariate, our approach provides additional flexibility in characterizing associations at different quantile levels. We apply the proposed approach to an analysis of air pollution and emergency department (ED) visits in Atlanta over 4 years. The analysis utilizes daily ZIP code-level distributions of personal exposures to 4 traffic-related ambient air pollutants simulated from the Stochastic Human Exposure and Dose Simulator. Our analyses find that effects of carbon monoxide on respiratory and cardiovascular disease ED visits are more pronounced with changes in lower quantiles of the population's exposure. Software for implement is provided in the R package nbRegQF.

Differential DNA methylation in the brain as potential mediator of the association between traffic-related PM2.5 and neuropathology markers of Alzheimer's disease.

INTRODUCTION: Growing evidence indicates that fine particulate matter (PM2.5) is a risk factor for Alzheimer's disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as a potential mediator of this association. METHODS: We assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors' residential traffic-related PM2.5 exposure 1, 3, and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs. RESULTS: PM2.5 was significantly associated with differential DNAm at cg25433380 and cg10495669. Twenty-four CpG sites were identified as mediators of the association between PM2.5 exposure and neuropathology markers, several located in genes related to neuroinflammation. DISCUSSION: Our findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM2.5 and AD. HIGHLIGHTS: First study to evaluate the potential mediation effect of DNA methylation for the association between PM2.5 exposure and neuropathological changes of Alzheimer's disease. Study was based on brain tissues rarely investigated in previous air pollution research. Cg10495669, assigned to RBCK1 gene playing a role in inflammation, was associated consistently with 1-year, 3-year, and 5-year traffic-related PM2.5 exposures prior to death. Meet-in-the-middle approach and high-dimensional mediation analysis were used simultaneously to increase the potential of identifying the differentially methylated CpGs. Differential DNAm related to neuroinflammation was found to mediate the association between traffic-related PM2.5 and Alzheimer's disease.

Assessment of census-tract level socioeconomic position as a modifier of the relationship between short-term PM2.5 exposure and cardiovascular emergency department visits in Missouri.

INTRODUCTION: Ambient particulate matter ≤ 2.5 µm in aerodynamic diameter (PM2.5) exposure elevates the risk for cardiovascular disease morbidity (CVDM). The aim of this study is to characterise which area-level measures of socioeconomic position (SEP) modify the relationship between PM2.5 exposure and CVDM in Missouri at the census-tract (CT) level. METHODS: We use individual level Missouri emergency department (ED) admissions data (n=3 284 956), modelled PM2.5 data, and yearly CT data from 2012 to 2016 to conduct a two-stage analysis. Stage one uses a case-crossover approach with conditional logistic regression to establish the baseline risk of ED visits associated with IQR changes in PM2.5. In the second stage, we use multivariate metaregression to examine how CT-level SEP modifies the relationship between ambient PM2.5 exposure and CVDM. RESULTS: We find that overall, ambient PM2.5 exposure is associated with increased risk for CVDM. We test effect modification in statewide and urban CTs, and in the warm season only. Effect modification results suggest that among SEP measures, poverty is most consistently associated with increased risk for CVDM. For example, across Missouri, the highest poverty CTs are at an elevated risk for CVDM (OR=1.010 (95% CI 1.007 to 1.014)) compared with the lowest poverty CTs (OR=1.004 (95% CI 1.000 to 1.008)). Other SEP modifiers generally display an inconsistent or null effect. CONCLUSION: Overall, we find some evidence that area-level SEP modifies the relationship between ambient PM2.5 exposure and CVDM, and suggest that the relationship between air-pollution, area-level SEP and CVDM may be sensitive to spatial scale.

Association of PM2.5 Exposure and Alzheimer Disease Pathology in Brain Bank Donors-Effect Modification by APOE Genotype.

BACKGROUND AND OBJECTIVES: Fine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer disease (AD) and is hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. The APOE gene, a major genetic risk factor of AD, has been hypothesized to modify the association between PM2.5 and AD. However, little prior research exists to support these hypotheses. This study investigates the association between traffic-related PM2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort. METHODS: A cross-sectional study was conducted using brain tissue donors enrolled in the Emory Goizueta AD Research Center who died before 2020 (n = 224). Donors were assessed for AD pathology including the Braak stage, Consortium to Establish a Registry for AD (CERAD) score, and combined AD neuropathologic change (ABC) score. Traffic-related PM2.5 concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250 m. One-year, 3-year, and 5-year average PM2.5 concentrations before death were matched to participants' home address. We assessed the association between traffic-related PM2.5 and AD hallmark pathology and effect modification by APOE genotype, using adjusted ordinal logistic regression models. RESULTS: Among the 224 participants, the mean age of death was 76 years, and 57% had at least 1 APOE ε4 copy. Traffic-related PM2.5 was significantly associated with the CERAD score for the 1-year exposure window (odds ratio [OR] 1.92; 95% CI 1.12-3.30) and the 3-year exposure window (OR 1.87; 95% CI 1.01-3.17). PM2.5 was also associated with higher Braak stage and ABC score albeit nonsignificantly. The strongest associations between PM2.5 and neuropathology markers were among those without APOE ε4 alleles (e.g., for the CERAD score and 1-year exposure window, OR 2.31; 95% CI 1.36-3.94), though interaction between PM2.5 and APOE genotype was not statistically significant. DISCUSSION: Our study found traffic-related PM2.5 exposure was associated with the CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM2.5 affects ß-amyloid deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this association.

Time-series analysis of temperature variability and cardiovascular emergency department visits in Atlanta over a 27-year period.

BACKGROUND: Short-term temperature variability, defined as the temperature range occurring within a short time span at a given location, appears to be increasing with climate change. Such variation in temperature may influence acute health outcomes, especially cardiovascular diseases (CVD). Most research on temperature variability has focused on the impact of within-day diurnal temperature range, but temperature variability over a period of a few days may also be health-relevant through its impact on thermoregulation and autonomic cardiac functioning. To address this research gap, this study utilized a database of emergency department (ED) visits for a variety of cardiovascular health outcomes over a 27-year period to investigate the influence of three-day temperature variability on CVD. METHODS: For the period of 1993-2019, we analyzed over 12 million CVD ED visits in Atlanta using a Poisson log-linear model with overdispersion. Temperature variability was defined as the standard deviation of the minimum and maximum temperatures during the current day and the previous two days. We controlled for mean temperature, dew point temperature, long-term time trends, federal holidays, and day of week. We stratified the analysis by age group, season, and decade. RESULTS: All cardiovascular outcomes assessed, except for hypertension, were positively associated with increasing temperature variability, with the strongest effects observed for stroke and peripheral vascular disease. In stratified analyses, adverse associations with temperature variability were consistently highest in the moderate-temperature season (October and March-May) and in the 65 + age group for all outcomes. CONCLUSIONS: Our results suggest that CVD morbidity is impacted by short-term temperature variability, and that patients aged 65 and older are at increased risk. These effects were more pronounced in the moderate-temperature season and are likely driven by the Spring season in Atlanta. Public health practitioners and patient care providers can use this knowledge to better prepare patients during seasons with high temperature variability or ahead of large shifts in temperature.

Associations between short-term ambient temperature exposure and emergency department visits for amphetamine, cocaine, and opioid use in California from 2005 to 2019.

Substance use disorder is a growing public health challenge in the United States. People who use drugs may be more vulnerable to ambient heat due to the effects of drugs on thermoregulation and their risk environment. There have been limited population-based studies of ambient temperature and drug-related morbidity. We examined short-term associations between daily ambient temperature and emergency department (ED) visits for use or overdose of amphetamine, cocaine and opioids in California during the period 2005 to 2019. Daily ZIP code-level maximum, mean, and minimum temperature exposures were derived from 1-km data Daymet products. A time-stratified case-crossover design was used to estimate cumulative non-linear associations of daily temperature for lag days 0 to 3. Stratified analyses by patient sex, race, and ethnicity were also conducted. The study included over 3.4 million drug-related ED visits. We found positive associations between daily temperature and ED visits for all outcomes examined. An increase in daily mean temperature from the 50th to the 95th percentile was associated with ED visits for amphetamine use (OR = 1.072, 95% CI: 1.058, 1.086), cocaine use (OR = 1.044, 95% CI: 1.021, 1.068 and opioid use (OR = 1.041, 95% CI: 1.025, 1.057). Stronger positive associations were also observed for overdose: amphetamine overdose (OR = 1.150, 95% CI: 1.085, 1.218), cocaine overdose (OR = 1.159, 95% CI: 1.053, 1.276), and opioid overdose (OR = 1.079, 95% CI: 1.054, 1.106). In summary, people who use stimulants and opioids may be a subpopulation sensitive to short-term higher ambient temperature. Mitigating heat exposure can be considered in harm reduction strategies in response to the substance use epidemic and global climate change.

Evaluating Data Product Exposure Metrics for Use in Epidemiologic Studies of Dust Storms.

Dust storms are increasing in frequency and correlate with adverse health outcomes but remain understudied in the United States (U.S.), partially due to the limited spatio-temporal coverage, resolution, and accuracy of current data sets. In this work, dust-related metrics from four public areal data products were compared to a monitor-based "gold standard" dust data set. The data products included the National Weather Service (NWS) storm event database, the Modern-Era Retrospective analysis for Research and Applications-Version 2, the EPA's Air QUAlity TimE Series (EQUATES) Project using the Community Multiscale Air Quality Modeling System (CMAQ), and the Copernicus Atmosphere Monitoring Service global reanalysis product. California, Nevada, Utah, and Arizona, which account for most dust storms reported in the U.S., were examined. Dichotomous and continuous metrics based on reported dust storms, particulate matter concentrations (PM10 and PM2.5), and aerosol-type variables were extracted or derived from the data products. Associations between these metrics and a validated dust storm detection method utilizing Interagency Monitoring of Protected Visual Environments monitors were estimated via quasi-binomial regression. In general, metrics from CAMS yielded the strongest associations with the "gold standard," followed by the NWS storm database metric. Dust aerosol (0.9-20 µm) mixing ratio, vertically integrated mass of dust aerosol (9-20 µm), and dust aerosol optical depth at 550 nm from CAMS generated the highest standardized odds ratios among all metrics. Future work will apply machine-learning methods to the best-performing metrics to create a public dust storm database suitable for long-term epidemiologic studies.

Differential DNA Methylation in the Brain as Potential Mediator of the Association between Traffic-related PM2.5 and Neuropathology Markers of Alzheimer's Disease.

INTRODUCTION: Growing evidence indicates fine particulate matter (PM2.5) as risk factor for Alzheimer's' disease (AD), but the underlying mechanisms have been insufficiently investigated. We hypothesized differential DNA methylation (DNAm) in brain tissue as potential mediator of this association. METHODS: We assessed genome-wide DNAm (Illumina EPIC BeadChips) in prefrontal cortex tissue and three AD-related neuropathological markers (Braak stage, CERAD, ABC score) for 159 donors, and estimated donors' residential traffic-related PM2.5 exposure 1, 3 and 5 years prior to death. We used a combination of the Meet-in-the-Middle approach, high-dimensional mediation analysis, and causal mediation analysis to identify potential mediating CpGs. RESULTS: PM2.5 was significantly associated with differential DNAm at cg25433380 and cg10495669. Twenty-six CpG sites were identified as mediators of the association between PM2.5 exposure and neuropathology markers, several located in genes related to neuroinflammation. DISCUSSION: Our findings suggest differential DNAm related to neuroinflammation mediates the association between traffic-related PM2.5 and AD.

The Association Between Ambient Temperature and Snakebite in Georgia, USA: A Case-Crossover Study.

The World Health Organization has identified snakebite envenoming as a highest priority neglected tropical disease, yet there is a dearth of epidemiologic research on environmental risk factors, including outdoor temperature. Temperature may affect snakebites through human behavior or snake behavior; snakes are ectotherms, meaning outdoor temperatures influence their internal body temperature and thus their behavior. Here we investigate the relationship between short-term temperature and snakebites in Georgia, one of the most biodiverse US states in terms of herpetofauna. We acquired emergency department (ED) visit data for Georgia between 1 January 2014 and 31 December 2020. Visits for venomous and non-venomous snakebites were identified using diagnosis codes. For comparison, we also considered visits for non-snake (e.g., insects, spiders, scorpions) envenomation. Daily meteorology from the Daymet 1 km product was linked to patient residential ZIP codes. We applied a case-crossover design to estimate associations of daily maximum temperature and snakebite ED visits. During the 7-year study period, there were 3,908 visits for venomous snakebites, 1,124 visits for non-venomous bites and 65,187 visits for non-snake envenomation. Across the entire period, a 1°C increase in same-day maximum temperature was associated with a 5.6% (95%CI: 4.0-7.3) increase in the odds of venomous snakebite and a 5.8% (95%CI: 3.0-8.8) increase in non-venomous snakebite. Associations were strongest in the spring. We also observed a positive and significant (p < 0.05) association for non-snake envenomation, albeit slightly smaller and more consistent across seasons compared to those for snakebites.

Pollen and asthma morbidity in Atlanta: A 26-year time-series study.

BACKGROUND: Compared to many environmental risk factors, the relationship between pollen and asthma is understudied, including how associations may differ by pollen type and between subgroups, and how associations may be changing over time. OBJECTIVES: We evaluated the association between ambient pollen concentrations and emergency department (ED) visits for asthma and wheeze in Atlanta, Georgia during 1993-2018. We estimated overall associations for 13 individual pollen taxa, as well as associations by decade, race, age (5-17, 18-64, 65+), and insurance status (Medicaid vs non-Medicaid). METHODS: Speciated pollen data were acquired from Atlanta Allergy & Asthma, a nationally certified pollen counting station. ED visit data were obtained from individual hospitals and from the Georgia Hospital Association. We performed time-series analyses using quasi-Poisson distributed lag models, with primary analyses assessing 3-day (lag 0-2 days) pollen levels. Models controlled for day of week, holidays, air temperature, month, year, and month-by-year interactions. RESULTS: From 1993 to 2018, there were 686,259 ED visits for asthma and wheeze in the dataset, and the number of ED visits increased over time. We observed positive associations of asthma and wheeze ED visits with nine of the 13 pollen taxa: trees (maple, birch, pine, oak, willow, sycamore, and mulberry), two weeds (nettle and pigweed), and grasses. Rate ratios indicated 1-8% increases in asthma and wheeze ED visits per standard deviation increases in pollen. In general, we observed stronger associations in the earliest period (1993-2000), in younger people, and in Black patients; however, results varied by pollen taxa. CONCLUSIONS: Some, but not all, types of pollen are associated with increased ED visits for asthma/wheeze. Associations are generally higher in Black and younger patients and appear to have decreased over time.

Are children with sickle cell disease at particular risk from the harmful effects of air pollution? Evidence from a large, urban/peri-urban cohort.

INTRODUCTION: Pathophysiologic pathways of sickle cell disease (SCD) and air pollution involve inflammation, oxidative stress, and endothelial damage. It is therefore plausible that children with SCD are especially prone to air pollution's harmful effects. METHODS: Patient data were collected from a single-center, urban/peri-urban cohort of children with confirmed SCD. Daily ambient concentrations of particulate matter (PM2.5 ) were collected via satellite-derived remote-sensing technology, and carbon monoxide (CO), nitrogen dioxide (NO2 ), and ozone from local monitoring stations. We used multivariable regression to quantify associations of pollutant levels and daily counts of emergency department (ED) visits, accounting for weather and time trends. For comparison, we quantified the associations of pollutant levels with daily all-patient (non-SCD) ED visits to our center. RESULTS: From 2010 to 2018, there were 17,731 ED visits by 1740 children with SCD (64.8% HbSS/HbSß0 ). Vaso-occlusive events (57.8%), respiratory illness (17.1%), and fever (16.1%) were the most common visit diagnoses. Higher 3-day (lags 0-2) rolling mean PM2.5 and CO levels were associated with daily ED visits among those with SCD (PM2.5 incident rate ratio [IRR] 1.051 [95% confidence interval: 1.010-1.094] per 9.4 µg/m3 increase; CO 1.088 [1.045-1.132] per 0.5 ppm). NO2 showed positive associations in secondary analyses; ozone levels were not associated with ED visits. The comparison, all-patient ED visit analyses showed lower IRR for all pollutants. CONCLUSIONS: Our results suggest short-term air pollution levels as triggers for SCD events and that children with SCD may be more vulnerable to air pollution than those without SCD. Targeted pollution-avoidance strategies could have significant clinical benefits in this population.

Acute Effects of Ambient Air Pollution on Asthma Emergency Department Visits in Ten U.S. States.

BACKGROUND: Previous studies of short-term ambient air pollution exposure and asthma morbidity in the United States have been limited to a small number of cities and/or pollutants and with limited consideration of effects across ages. OBJECTIVES: To estimate acute age group-specific effects of fine and coarse particulate matter (PM), major PM components, and gaseous pollutants on emergency department (ED) visits for asthma during 2005-2014 across the United States. METHODS: We acquired ED visit and air quality data in regions surrounding 53 speciation sites in 10 states. We used quasi-Poisson log-linear time-series models with unconstrained distributed exposure lags to estimate site-specific acute effects of air pollution on asthma ED visits overall and by age group (1-4, 5-17, 18-49, 50-64, and 65+ y), controlling for meteorology, time trends, and influenza activity. We then used a Bayesian hierarchical model to estimate pooled associations from site-specific associations. RESULTS: Our analysis included 3.19 million asthma ED visits. We observed positive associations for multiday cumulative exposure to all air pollutants examined [e.g., 8-d exposure to PM2.5: rate ratio of 1.016 with 95% credible interval (CI) of (1.008, 1.025) per 6.3-µg/m3 increase, PM10-2.5: 1.014 (95% CI: 1.007, 1.020) per 9.6-µg/m3 increase, organic carbon: 1.016 (95% CI: 1.009, 1.024) per 2.8-µg/m3 increase, and ozone: 1.008 (95% CI: 0.995, 1.022) per 0.02-ppm increase]. PM2.5 and ozone showed stronger effects at shorter lags, whereas associations of traffic-related pollutants (e.g., elemental carbon and oxides of nitrogen) were generally stronger at longer lags. Most pollutants had more pronounced effects on children (<18 y old) than adults; PM2.5 had strong effects on both children and the elderly (>64 y old); and ozone had stronger effects on adults than children. CONCLUSIONS: We reported positive associations between short-term air pollution exposure and increased rates of asthma ED visits. We found that air pollution exposure posed a higher risk for children and older populations. https://doi.org/10.1289/EHP11661.

Fine particulate air pollution and neuropathology markers of Alzheimer's disease in donors with and without APOE ε4 alleles - results from an autopsy cohort.

Introduction: Higher fine particulate matter (PM2.5) exposure has been found to be associated with Alzheimer's disease (AD). PM2.5 has been hypothesized to cause inflammation and oxidative stress in the brain, contributing to neuropathology. A major genetic risk factor of AD, the apolipoprotein E (APOE) gene, has also been hypothesized to modify the association between PM2.5 and AD. However, little prior research exisits to support these hypotheses. Therefore, this paper aims to investigate the association between traffic-related PM2.5 and AD hallmark pathology, including effect modification by APOE genotype, in an autopsy cohort. Methods: Brain tissue donors enrolled in the Emory Goizueta Alzheimer's Disease Research Center (ADRC) who died before 2020 (n=224) were assessed for AD pathology including Braak Stage, Consortium to Establish a Registry for AD (CERAD) score, and the combined AD neuropathologic change (ABC score). Traffic-related PM2.5 concentrations were modeled for the metro-Atlanta area during 2002-2019 with a spatial resolution of 200-250m. One-, 3-, and 5-year average PM2.5 concentrations prior to death were matched to participants home address. We assessed the association between traffic-related PM2.5 and AD hallmark pathology, as well as effect modification by APOE genotype, using adjusted ordinal logistic regression models. Results: Traffic-related PM2.5 was significantly associated with CERAD score for the 1-year exposure window (OR: 1.92; 95% CI: 1.12, 3.30), and the 3-year exposure window (OR: 1.87; 95%-CI: 1.01, 3.17). PM2.5 had harmful, but non-significant associations on Braak Stage and ABC score. The strongest associations between PM2.5 and neuropathology markers were among those without APOE ε4 alleles (e.g., for CERAD and 1-year exposure window, OR: 2.31; 95% CI: 1.36, 3.94), though interaction between PM2.5 and APOE genotype was not statistically significant. Conclusions: Our study found traffic-related PM2.5 exposure was associated with CERAD score in an autopsy cohort, contributing to epidemiologic evidence that PM2.5 affects Aß deposition in the brain. This association was particularly strong among donors without APOE ε4 alleles. Future studies should further investigate the biological mechanisms behind this assocation.

Short-term associations between ambient air pollution and emergency department visits for Alzheimer's disease and related dementias.

Dementia is a seriously disabling illness with substantial economic and social burdens. Alzheimer's disease and its related dementias (AD/ADRD) constitute about two-thirds of dementias. AD/ADRD patients have a high prevalence of comorbid conditions that are known to be exacerbated by exposure to ambient air pollution. Existing studies mostly focused on the long-term association between air pollution and AD/ADRD morbidity, while very few have investigated short-term associations. This study aims to estimate short-term associations between AD/ADRD emergency department (ED) visits and three common air pollutants: fine particulate matter (PM2.5), nitrogen dioxide (NO2), and warm-season ozone. Methods: For the period 2005 to 2015, we analyzed over 7.5 million AD/ADRD ED visits in five US states (California, Missouri, North Carolina, New Jersey, and New York) using a time-stratified case-crossover design with conditional logistic regression. Daily estimated PM2.5, NO2, and warm-season ozone concentrations at 1 km spatial resolution were aggregated to the ZIP code level as exposure. Results: The most consistent positive association was found for NO2. Across five states, a 17.1 ppb increase in NO2 concentration over a 4-day period was associated with a 0.61% (95% confidence interval = 0.27%, 0.95%) increase in AD/ADRD ED visits. For PM2.5, a positive association with AD/ADRD ED visits was found only in New York (0.64%, 95% confidence interval = 0.26%, 1.01% per 6.3 µg/m3). Associations with warm-season ozone levels were null. Conclusions: Our results suggest AD/ADRD patients are vulnerable to short-term health effects of ambient air pollution and strategies to lower exposure may reduce morbidity.

Monitoring vs. modeled exposure data in time-series studies of ambient air pollution and acute health outcomes.

BACKGROUND: Population-based short-term air pollution health studies often have limited spatiotemporally representative exposure data, leading to concerns of exposure measurement error. OBJECTIVE: To compare the use of monitoring and modeled exposure metrics in time-series analyses of air pollution and cardiorespiratory emergency department (ED) visits. METHODS: We obtained daily counts of ED visits for Atlanta, GA during 2009-2013. We leveraged daily ZIP code level concentration estimates for eight pollutants from nine exposure metrics. Metrics included central monitor (CM), monitor-based (inverse distance weighting, kriging), model-based [community multiscale air quality (CMAQ), land use regression (LUR)], and satellite-based measures. We used Poisson models to estimate air pollution health associations using the different exposure metrics. The approach involved: (1) assessing CM-based associations, (2) determining if non-CM metrics can reproduce CM-based associations, and (3) identifying potential value added of incorporating full spatiotemporal information provided by non-CM metrics. RESULTS: Using CM exposures, we observed associations between cardiovascular ED visits and carbon monoxide, nitrogen dioxide, fine particulate matter, elemental and organic carbon, and between respiratory ED visits and ozone. Non-CM metrics were largely able to reproduce CM-based associations, although some unexpected results using CMAQ- and LUR-based metrics reduced confidence in these data for some spatiotemporally-variable pollutants. Associations with nitrogen dioxide and sulfur dioxide were only detected, or were stronger, when using metrics that incorporate all available monitoring data (i.e., inverse distance weighting and kriging). SIGNIFICANCE: The use of routinely-collected ambient monitoring data for exposure assignment in time-series studies of large metropolitan areas is a sound approach, particularly when data from multiple monitors are available. More sophisticated approaches derived from CMAQ, LUR, or satellites may add value when monitoring data are inadequate and if paired with thorough data characterization. These results are useful for interpretation of existing literature and for improving exposure assessment in future studies. IMPACT STATEMENT: This study compared and interpreted the use of monitoring and modeled exposure metrics in a daily time-series analysis of air pollution and cardiorespiratory emergency department visits. The results suggest that the use of routinely-collected ambient monitoring data in population-based short-term air pollution and health studies is a sound approach for exposure assignment in large metropolitan regions. CMAQ-, LUR-, and satellite-based metrics may allow for health effects estimation when monitoring data are sparse, if paired with thorough data characterization. These results are useful for interpretation of existing health effects literature and for improving exposure assessment in future air pollution epidemiology studies.

Short-term associations between warm-season ambient temperature and emergency department visits for Alzheimer's disease and related dementia in five US states.

BACKGROUND: Ambient temperatures are projected to increase in the future due to climate change. Alzheimer's disease (AD) and Alzheimer's disease-related dementia (ADRD) affect millions of individuals and represent substantial health burdens in the US. High temperature may be a risk factor for AD/ADRD outcomes with several recent studies reporting associations between temperature and AD mortality. However, the link between heat and AD morbidity is poorly understood. METHODS: We examined short-term associations between warm-season daily ambient temperature and AD/ADRD emergency department (ED) visits for individuals aged 45 years or above during the warm season (May to October) for up to 14 years (2005-2018) in five US states: California, Missouri, North Carolina, New Jersey, and New York. Daily ZIP code-level maximum, average and minimum temperature exposures were derived from 1 km gridded Daymet products. Associations are assessed using a time-stratified case-crossover design using conditional logistic regression. RESULTS: We found consistent positive short-term effects of ambient temperature among 3.4 million AD/ADRD ED visits across five states. An increase of the 3-day cumulative temperature exposure of daily average temperature from the 50th to the 95th percentile was associated with a pooled odds ratio of 1.042 (95% CI: 1.034, 1.051) for AD/ADRD ED visits. We observed evidence of the association being stronger for patients 65-74 years of age and for ED visits that led to hospital admissions. Temperature associations were also stronger among AD/ADRD ED visits compared to ED visits for other reasons, particularly among patients aged 65-74 years. CONCLUSION: People with AD/ADRD may represent a vulnerable population affected by short-term exposure to high temperature. Our results support the development of targeted strategies to reduce heat-related AD/ADRD morbidity in the context of global warming.