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Background: Clonal hematopoiesis of indeterminate potential (CHIP) is an age-related somatic mutation associated with incident hematologic cancer. Environmental stressors which, like air pollution, generate oxidative stress at the cellular level, may induce somatic mutations and some mutations may provide a selection advantage for persistence and expansion of specific clones. Methods: We used data from the Multi-Ethnic Study of Atherosclerosis (MESA) N = 4,379 and the Women's Health Initiative (WHI) N = 7,701 to estimate cross-sectional associations between annual average air pollution concentrations at participant address the year before blood draw using validated spatiotemporal models. We used covariate-adjusted logistic regression to estimate risk of CHIP per interquartile range increases in particulate matter (PM2.5; 4 µg/m3) and nitrogen dioxide (NO2; 10 ppb) as ORs (95% confidence intervals). Results: Prevalence of CHIP at blood draw (variant allele fraction > 2%) was 4.4% and 8.7% in MESA and WHI, respectively. The most common CHIP driver mutation was in DNMT3A. Neither pollutant was associated with CHIP: ORMESA PM2.5 = 1.00 (0.68-1.45), ORMESA NO2 = 1.05 (0.69-1.61), ORWHI PM2.5 = 0.97 (0.86-1.09), ORWHI NO2 = 0.98 (0.88-1.10); or with DNMT3A-driven CHIP. Conclusions: We did not find evidence that air pollution contributes to CHIP prevalence in two large observational cohorts. Impact: This is the first study to estimate associations between air pollution and CHIP. [ABSTRACT FROM AUTHOR]

Traffic-related air pollution (TRAP), a common exposure, potentially impacts pregnancy through altered placental function. We investigated associations between prenatal TRAP exposure and placental gene expression. Whole transcriptome sequencing was performed on placental samples from CANDLE (Memphis, TN) (n = 776) and GAPPS (Seattle and Yakima, WA) (n = 205), cohorts of the ECHO-PATHWAYS Consortium. Residential NO 2 exposures were computed via spatiotemporal models for full-pregnancy, each trimester, and the first/last months of pregnancy. Individual cohort-specific, covariate-adjusted linear models were fit for 10,855 genes and respective exposures (NO 2 or roadway proximity [≤150 m]). Infant-sex/exposure interactions on placental gene expression were tested with interaction terms in separate models. Significance was based on false discovery rate (FDR<0.10). In GAPPS, final-month NO 2 exposure was positively associated with MAP1LC3C expression (FDR p-value = 0.094). Infant-sex interacted with second-trimester NO 2 on STRIP2 expression (FDR interaction p-value = 0.011, inverse and positive associations among male and female infants, respectively) and roadway proximity on CEBPA expression (FDR interaction p-value = 0.045, inverse among females). In CANDLE, infant-sex interacted with first-trimester and full-pregnancy NO 2 on RASSF7 expression (FDR interaction p-values = 0.067 and 0.013, respectively, positive among male infants and inverse among female infants). Overall, pregnancy NO 2 exposure and placental gene expression associations were primarily null, with exception of final month NO 2 exposure and placental MAP1LC3C association. We found several interactions of infant sex and TRAP exposures on placental expression of STRIP2 , CEBPA , and RASSF7. These highlighted genes suggest influence of TRAP on placental cell proliferation, autophagy, and growth, though additional replication and functional studies are required for validation. • Cohort-specific association of NO 2 exposure with placenta MAP1LC3C expression. • Cohort-specific infant-sex/NO 2 interaction on placenta ZDBF2 and RASSF7 expression. • Cohort-specific infant-sex/road-proximity interaction on placenta CEBPA expression. [ABSTRACT FROM AUTHOR]

Background: Infants experiencing bronchiolitis are at increased risk for asthma, but few studies have identified modifiable risk factors. We assessed whether early life air pollution influenced child asthma and wheeze at age 4-6 years among children with a history of bronchiolitis in the first postnatal year. Methods: Children with caregiver-reported physician-diagnosed bronchiolitis were drawn from ECHO-PATHWAYS, a pooled longitudinal cohort from six US cities. We estimated their air pollution exposure from age 1 to 3 years from validated spatiotemporal models of fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3). Caregivers reported children's current wheeze and asthma at age 4-6 years. We used modified Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CI), adjusting for child, maternal, and home environmental factors. We assessed effect modification by child sex and maternal history of asthma with interaction models. Results: A total of 224 children had caregiver-reported bronchiolitis. Median (interquartile range) 2-year pollutant concentrations were 9.3 (7.8-9.9) µg/m3 PM2.5, 8.5 (6.4-9.9) ppb NO2, and 26.6 (25.6-27.7) ppb O3. RRs (CI) for current wheeze per 2-ppb higher O3 were 1.3 (1.0-1.7) and 1.4 (1.1-1.8) for asthma. NO2 was inversely associated with wheeze and asthma whereas associations with PM2.5 were null. We observed interactions between NO2 and PM2.5 and maternal history of asthma, with lower risks observed among children with a maternal history of asthma. Conclusion: Our results are consistent with the hypothesis that exposure to modest postnatal O3 concentrations increases the risk of asthma and wheeze among the vulnerable subpopulation of infants experiencing bronchiolitis. [ABSTRACT FROM AUTHOR]

Background: Late‐life ambient air pollution exposures are associated with increased Alzheimer's disease (AD) risk1. Cortical thinning in temporal areas vulnerable to AD is associated with memory decline, neuropathological changes, and increased AD risk. However, most neuroimaging studies on air pollution neurotoxicity analyzed volumetric indices that are not sensitive to early cortical changes, and focused on discrete regions of interest (ROI) selected a priori rather than taking an ROI approach across the whole brain. Therefore, the mechanisms linking exposures to early neuropathological processes in older age are poorly understood. Method: We examined data from 1068 cognitively unimpaired women from the Women's Health Initiative Memory Study who underwent neuroimaging in 2005‐6 (Meanage = 77.8±3.7). Long‐term residential exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were quantified as the 3‐year average of monthly estimates prior to MRI using spatiotemporal models with regionalized universal kriging. Brain scans were processed using FreeSurfer‐v.5.3.0 to estimate cortical thickness in 34 bilateral regions parcellated with the Desikan‐Killiany atlas. Exposure effects on AD‐vulnerable regions were assessed by calculating an AD signature (higher value representing thicker cortices) of surface‐area‐weighted thickness in the bilateral entorhinal, fusiform, inferior temporal, and middle temporal cortices2. We used linear mixed models to estimate exposure effects on standardized regional cortical thickness and the AD signature, adjusting for sociodemographic, lifestyle, and clinical characteristics, and a random effect for scanner manufacturer. Result: After adjusting for covariates and multiple comparisons using the False discovery rate (FDR) method, higher exposures to PM2.5 and NO2 were associated with thinner cortices in at least 31 brain regions (FDR‐adjusted p's<0.05). There were also significant adverse effects of PM2.5 (β = ‐0.055, 95%CI = [‐0.07,‐0.04] per 1µg/m3) and NO2 (β = ‐0.022, 95%CI = [‐0.03,‐0.01] per 1ppb) on the AD signature, equivalent to 1.1 and 0.5 years of aging, respectively. Across all analyses the strongest effects were observed in the frontal lobe, especially the motor cortex. Conclusion: In cognitively unimpaired older women, higher exposures to PM2.5 and NO2 were associated with widespread cortical thinning, including regions sensitive to AD. However, the strongest associations in the frontal lobe suggest a greater impact of air pollution neurotoxicity on brain aging rather than AD risk. [ABSTRACT FROM AUTHOR]

Introduction: Growing evidence implicates air pollution as a risk factor for dementia, but prior work is limited by challenges in diagnostic accuracy and assessing exposures in the decades prior to disease development. We evaluated the impact of long‐term fine particulate matter (PM2.5) exposures on incident dementia (all‐cause, Alzheimer's disease [AD], and vascular dementia [VaD]) in older adults. Methods: A panel of neurologists adjudicated dementia cases based on extensive neuropsychological testing and magnetic resonance imaging. We applied validated fine‐scale air pollutant models to reconstructed residential histories to assess exposures. Results: An interquartile range increase in 20‐year PM2.5 was associated with a 20% higher risk of dementia (95% confidence interval [CI]: 5%, 37%) and an increased risk of mixed VaD/AD but not AD alone. Discussion: Our findings suggest that air pollutant exposures over decades contribute to dementia and that effects of current exposures may be experienced years into the future. [ABSTRACT FROM AUTHOR]

Introduction: Particulate air pollutants may induce neurotoxicity by increasing homocysteine levels, which can be lowered by high B vitamin intakes. Therefore, we examined whether intakes of three B vitamins (folate, B12, and B6) modified the association between PM2.5 exposure and incidence of all‐cause dementia. Methods: This study included 7183 women aged 65 to 80 years at baseline. B vitamin intakes from diet and supplements were estimated by food frequency questionnaires at baseline. The 3‐year average PM2.5 exposure was estimated using a spatiotemporal model. Results: During a mean follow‐up of 9 years, 342 participants developed all‐cause dementia. We found that residing in locations with PM2.5 exposure above the regulatory standard (12 μg/m3) was associated with a higher risk of dementia only among participants with lower intakes of these B vitamins. Discussion: This is the first study suggesting that the putative neurotoxicity of PM2.5 exposure may be attenuated by high B vitamin intakes. [ABSTRACT FROM AUTHOR]

Background: An increased familial risk of breast cancer may be due to both shared genetics and environment. Women with a breast cancer family history may have a higher prevalence of breast cancer-related gene variants and thus increased susceptibility to environmental exposures. We evaluated whether air pollutant and breast cancer associations varied by familial risk. Methods: Sister Study participants living in the contiguous United States at enrollment (2003-2009; N = 48,453), all of whom had at least one first-degree relative with breast cancer, were followed for breast cancer. Annual NO2 and PM2.5 concentrations were estimated at the enrollment addresses. We predicted 1-year familial breast cancer risk using the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA). Using Cox regression, we estimated HRs and 95% confidence intervals (CI) for associations between each pollutant dichotomized at the median and breast cancer with interaction terms to examine modification by BOADICEA score. Results: NO2 was associated with a higher breast cancer risk among those with BOADICEA score >90th percentile (HR, 1.28; 95% CI, 1.05-1.56) but not among those with BOADICEA score ≤90th percentile (HR, 0.98; 95% CI, 0.90-1.06; Pinteraction = 0.01). In contrast to NO2, associations between PM2.5 and breast cancer did not vary between individuals with BOADICEA score >90th percentile and ≤90th percentile (Pinteraction = 0.26). Conclusions: Our results provide additional evidence that air pollution may be implicated in breast cancer, particularly among women with a higher familial risk. Impact: Women at higher underlying breast cancer risk may benefit more from interventions to reduce exposure to NO2. [ABSTRACT FROM AUTHOR]

[Figure: see text]. [ABSTRACT FROM AUTHOR]

Background: Exposure to air pollution in older adulthood is a novel risk factor for mild cognitive impairment (MCI). MCI is a heterogenous construct with different subtypes likely reflecting different disease etiologies. Understanding if long‐term exposure to air pollution is differentially associated with MCI subtypes may provide insight into the neurotoxic effects of air pollution exposure on the aging brain. Method: Participants included women from the Women's Health Initiative Memory Study. Data from 651 women without dementia who screened positive for cognitive impairment on the modified mini‐mental state examination (3MS) and a randomly selected comparison sample of 2,560 women who were cognitively intact based on the 3MS were utilized. Participants were administered the 3MS annually (1996‐2008). Those who screened positive for cognitive impairment on the 3MS completed the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) cognitive battery and the Trailmaking Test parts A and B. Average annual levels of particulate matter of aerodynamic diameter<2.5 (PM2.5) and nitrogen dioxide (NO2) were estimated at the participant's residence using regionalized national universal kriging models and averaged over the 3‐year period before the cognitive assessment. Latent class structural equation models (SEM) were constructed to identify MCI subtypes. We then examined associations between air pollution exposure and latent class membership using multinomial regression while adjusting for demographic, lifestyle, and clinical confounders. Result: Four significant MCI subtypes were identified (Figure 1): multidomain MCI (n = 147; 23%), amnestic MCI (n = 141; 22%), dysnomic/dysexecutive MCI (n = 200; 31%), and subtle MCI (n = 163; 25%). Women living in locations with higher levels of PM2.5 (per interquartile range [IQR] = 3.93 µg/m3; OR = 1.28; p =.04) or NO2 (per IQR = 9.25 ppb; OR = 1.36; p =.02) were more likely to be classified as having subtle MCI compared to normal comparisons. One IQR increase in NO2 was also associated with increased likelihood of being classified with dysnomic/dysexecutive MCI (OR = 1.38; p =.003) compared to normal comparisons. Conclusion: Our study illustrates that long‐term exposure to PM2.5 and NO2 may be associated with specific subtypes of MCI. Our findings provide further evidence that air pollution may exert neurotoxic effects on brain areas underlying executive function and language ability in older women. [ABSTRACT FROM AUTHOR]

Determining the most feasible and cost-effective approaches to improving PM 2.5 exposure assessment with low-cost monitors (LCMs) can considerably enhance the quality of its epidemiological inferences. We investigated features of fixed-site LCM designs that most impact PM 2.5 exposure estimates to be used in long-term epidemiological inference for the Adult Changes in Thought Air Pollution (ACT-AP) study. We used ACT-AP collected and calibrated LCM PM 2.5 measurements at the two-week level from April 2017 to September 2020 (N of monitors [measurements] = 82 [502]). We also acquired reference-grade PM 2.5 measurements from January 2010 to September 2020 (N = 78 [6186]). We used a spatiotemporal modeling approach to predict PM 2.5 exposures with either all LCM measurements or varying subsets with reduced temporal or spatial coverage. We evaluated the models based on a combination of cross-validation and external validation at locations of LCMs included in the models (N = 82), and also based on an independent external validation with a set of LCMs not used for the modeling (N = 30). We found that the model's performance declined substantially when LCM measurements were entirely excluded (spatiotemporal validation R2 [RMSE] = 0.69 [1.2 μg/m3]) compared to the model with all LCM measurements (0.84 [0.9 μg/m3]). Temporally, using the farthest apart measurements (i.e. , the first and last) from each LCM resulted in the closest model's performance (0.79 [1.0 μg/m3]) to the model with all LCM data. The models with only the first or last measurement had decreased performance (0.77 [1.1 μg/m3]). Spatially, the model's performance decreased linearly to 0.74 (1.1 μg/m3) when only 10% of LCMs were included. Our analysis also showed that LCMs located in densely populated, road-proximate areas improved the model more than those placed in moderately populated, road-distant areas. [Display omitted] • Addition of low-cost monitoring (LCM) sites can improve PM 2.5 model accuracy. • Use of LCM designs with longer time gaps optimizes spatiotemporal PM 2.5 prediction. • Deployment of LCMs in populated, road-proximate areas enhances PM 2.5 modeling. [ABSTRACT FROM AUTHOR]

Introduction: Exposure to noise might influence risk of Alzheimer's disease (AD) dementia. Methods: Participants of the Chicago Health and Aging Project (≥65 years) underwent triennial cognitive assessments. For the 5 years preceding each assessment, we estimated 5227 participants' residential level of noise from the community using a spatial prediction model, and estimated associations of noise level with prevalent mild cognitive impairment (MCI) and AD, cognitive performance, and rate of cognitive decline. Results: Among these participants, an increment of 10 A‐weighted decibels (dBA) in noise corresponded to 36% and 29% higher odds of prevalent MCI (odds ratio [OR] = 1.36; 95% confidence interval [CI], 1.15 to 1.62) and AD (OR = 1.29, 95% CI, 1.08 to 1.55). Noise level was associated with worse global cognitive performance, principally in perceptual speed (–0.09 standard deviation per 10 dBA, 95% CI: –0.16 to –0.03), but not consistently associated with cognitive decline. Discussion: These results join emerging evidence suggesting that noise may influence late‐life cognition and risk of dementia. [ABSTRACT FROM AUTHOR]

Background: Exposure to household air pollution (HAP) from cooking with biomass fuel affects billions of people. We hypothesized that HAP from woodsmoke, compared to other household fuels, was associated with adverse cardiovascular outcomes, of which there have been few studies. Methods: A cross-sectional study was completed in 299 females aged 40-70 years in Kaski District, Nepal, during 2017-18. All participants underwent a standard 12-lead ECG, ankle and brachial systolic blood pressure measurement, and 2D color and Doppler echocardiography. Current stove type was confirmed by inspection. Blood pressure, height, and weight were measured using a standardized protocol. Hypertension was defined as ≥140/90 mmHg or prior diagnosis. Hemoglobin A1c (HbA1c) was obtained, with diabetes mellitus defined as a prior diagnosis or HbA1C ≥ 6.5%. We used adjusted linear and logistic multivariable regressions to examine the relationship of stove type with cardiac structure and function. Results: The majority of women primarily used liquified petroleum gas (LPG) stoves (65%), while 12% used biogas, and 23% used wood-burning cook-stoves. Prevalence of major cardiovascular risk factors was 35% with hypertension, 19% with diabetes mellitus, and 15% current smokers. After adjustment, compared to LPG, wood stove use was associated with increased indexed left atrial volume (β = 3.15, 95% CI 1.22 to 5.09) and increased indexed left ventricular end diastolic volume (β = 7.97, 95% CI 3.11 to 12.83). There was no association between stove type and systemic hypertension, left ventricular mass, systolic dysfunction, diastolic dysfunction, pulmonary hypertension, abnormal ankle-brachial index, or clinically significant ECG abnormalities. Conclusion: Biomass fuel use was associated with increased indexed left atrial volume and increased indexed left ventricular diastolic volume in Nepali women, suggesting subclinical adverse cardiac remodeling from HAP in this cross-sectional study. We did not find evidence of an association with hypertension or typical cardiac sequelae of hypertension. Future studies to confirm these results are needed. [ABSTRACT FROM AUTHOR]

Background: Episodic memory (EM) declines vary by age and underlying neuropathology. Whether exposure to ambient air pollutants contributes to the observed heterogeneity of EM decline in older people is unclear. Method: We examined the associations between exposures and EM trajectories in the US‐based Women's Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO) cohort (N=2042, aged 74‐92 in 2008). EM was assessed annually (2008‐18) using the immediate recall total correct (3 trials) in the telephone‐based California Verbal Learning Test. Recent 3‐year average exposures to regional PM2.5 (particulate matter with aerodynamic diameter < 2.5μm) and NO2 (a proxy of traffic‐related air pollutants) and the corresponding remote 3‐year averages approximately at 10 years prior to inception were derived from yearly exposures estimated by regionalized national universal kriging. Latent‐class mixed models were used to classify EM trajectories and examine the exposure effect in each identified latent class. All models adjusted for social‐demographic factors, lifestyle, cardiovascular risk and other clinical covariates. Result: There were two latent EM trajectories that differed by WHIMS‐ECHO baseline age (≤80 vs. oldest‐old 80+; Figure 1) and exposure characteristics (Table 1). In women aged ≤80 (N=836), greater EM decline was associated with higher PM2.5 in the subgroup with slow‐decline (76%; −0.18/year), but not in those with fast‐decline (24%; −1.75/year). The observed association, equivalent to 1‐2 years of aging, was stronger for recent 3‐year exposure (−0.151/year, per inter‐quartile‐range [IQR]=2.86µg/m3, p=0.02), as compared with remote exposure (−0.096/year, per IQR=3.28µg/m3, p=0.09). In the oldest‐old (aged>80; N=1206), EM decline (70% steady decline by −1.37/year; 30% no apparent decline) was not associated with recent or remote PM2.5 exposures. In both age groups, no appreciable NO2 effects on EM decline were observed, and neither PM2.5 nor NO2 exposures during recent or remote years affected the levels of EM trajectories. Adjusted models further accounting for propensity scores of exposures revealed very similar results. Conclusion: The accelerated EM declines associated with late‐life exposures to ambient air pollutants vary by age‐related cognitive trajectories, exposure time‐windows and pollution sources. The observed association was most consistent with PM2.5 exposure during recent years in older women aged ≤80 with slow EM decline. [ABSTRACT FROM AUTHOR]

Background: Ambient air pollutants are toxic to the vascular systems, and recent studies have shown the late‐life exposures may result in neurodegeneration and increased risks for AD. It is unclear if cerebrovascular damage and AD‐related neurodegeneration contribute to the atrophies of medial temporal lobe. Here we assessed whether AD related neurodegeneration and cerebrovascular disease mediated adverse effects of air pollution exposure on MTL atrophy. Method: Participants included 624 community‐dwelling older women without dementia (mean age 77.4 +/‐ 3.4 years) who underwent two structural brain MRI scans (MRI‐1: 2005‐6; MRI‐2: 2010‐11) as part of the Women's Health Initiative Memory Study. Regionalized universal kriging was used to estimate annual concentrations of PM2.5 (fine particulate matter) and NO2 at residential locations aggregated to 3‐year averages prior to MRI‐1. The outcome was 5‐year standardized change in the MTL volumes. Mediators included spatial pattern of neurodegeneration of AD (AD pattern similarity scores [ADPS], validated ADNI data) and a proxy of global cerebrovascular damage (small‐vessel ischemic disease [SVID]). Whether the associations between exposures on MTL atrophy were mediated by the initial level or concurrent change in ADPS or global SVID were examined by the structural equation models with latent‐difference scores. All effect paths were adjusted for sociodemographic, lifestyle, clinical characteristics, and intracranial volume. Result: Living in locations with higher PM2.5 (per interquartile range [IQR] = 3.21µg/m3) and NO2 (per IQR = 6.72ppb) were both associated with greater atrophy of the MTL (βPM2.5 = ‐.27, 95% confidence interval [CI] = [‐.38,‐.16]; βNO2 = ‐.12,95%CI = [‐.22,‐.02]). PM2.5 was associated with increased ADPS (βPM2.5 =.02, 95%CI = [.01,.05]) over time, which partially mediated associations with MTL atrophy (26%, 95% CI = [10%,49%; Figure 1 Panel A). NO2 was positively associated with ADPS at MRI‐1 (βNO2 =.02, 95%CI = [.01,.04]), which partially mediated the association with MTL atrophy (14%, 95% CI = [1%,94%]; Figure 1 Panel B). Global SVID at MRI‐1 or change in SVID did not significantly mediate observed associations between exposures and MTL atrophy (Figure 1 Panels C and D). Conclusion: Our study supports the mediating role of AD neurodegeneration contributing to MTL atrophy associated with late‐life exposures to air pollutants. Findings support the hypothesis that multiple neuropathological processes of brain aging are affected by air pollution neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Ambient air pollution exposures increase the risk of Alzheimer's disease (AD) and related dementias, which may be driven by structural brain alterations in the medial temporal lobe (MTL). The MTL consists of subregions critical for memory and vulnerable to AD neuropathology, including the hippocampus, parahippocampal gyrus (PHG), entorhinal cortex (ERC), and amygdala. However, previous structural MRI studies examining the hypothesized adverse effects of exposure on MTL were cross‐sectional and largely focused on hippocampus which yielded mixed results, failing to provide insights on the underlying neuropathological processes affected by air pollution exposures. Method: We conducted a longitudinal study including 653 cognitively‐normal community‐dwelling women from the Women's Health Initiative Memory Study with two MRI brain scans (MRI‐1: 2005‐6; MRI‐2: 2010‐11; Meanage at MRI‐1 = 77.3±3.5). Using regionalized universal kriging models, exposures at residential locations were estimated as 3‐year annual averages of fine particulate matter (PM2.5) and nitrogen dioxide (NO2; traffic‐related pollution) prior to MRI‐1. Volumes of the total MTL and MTL subregions were derived using multi‐atlas region segmentation with ensembled registration. We used linear regressions to estimate exposure effects on 5‐year standardized volume changes, adjusting for intracranial volume, sociodemographic, lifestyle, and clinical characteristics. We also examined if associations differed between APOE4 carriers (n = 123) and non‐carriers (n = 463). Result: MTL volume decreased by 0.53±1.00cm3 over 5 years. For each interquartile increase of PM2.5 (3.26µg/m3) and NO2 (6.77ppb), adjusted MTL volume had greater shrinkage by 0.32cm3 (95%CI = [‐0.43,‐0.21]) and 0.12cm3 (95%CI = [‐0.23,‐0.01]) over 5 years, equivalent to respectively 17% (95%CI = [11%, 24%]) and 6% (95%CI = [0.6%, 12%]) increased dementia risk. For PHG, we found loss of 0.24cm3 (95%CI = [‐0.30,‐0.19]) and 0.09cm3 (95%CI = [‐0.14,‐0.04]) associated with PM2.5 and NO2 respectively. There was loss of 0.06cm3 (95%CI = [‐0.10,‐0.01]) in ERC associated with PM2.5, but not with NO2. No associations were found with amygdala or hippocampal atrophy. The observed adverse exposure effects on MTL atrophy did not differ by APOE4 genotype. Conclusion: MTL atrophy in older women was associated with late‐life exposures to PM2.5 and NO2, and the putative adverse effects varied across brain subregions. The PHG and ERC—the MTL subregions where AD neuropathologies likely begin, may be preferentially vulnerable to air pollution neurotoxicity. [ABSTRACT FROM AUTHOR]

Background: Few studies have examined associations of geographically proximal cigarette prices with within-person changes in smoking outcomes or assessed interactions between cigarette prices and smoking bans.Methods: We linked neighborhood cigarette prices (inflation-adjusted) at chain supermarkets and drug stores and bar/restaurant smoking ban policies to cohort participants (632 smokers from the Multi-Ethnic Study of Atherosclerosis, 2001-2012, baseline mean age 58 years) using geocoded retailer and participant addresses. We used fixed-effects models to investigate associations of within-person changes in price and ban exposures with within-person changes in five smoking outcomes: current smoking, heavy (≥10 cigarettes) smoking, cessation, relapse, and intensity (average number of cigarettes smoked per day, natural log transformed). We assessed intensity associations among all smokers, and heavy (≥10 cigarettes per day) and light (<10) baseline smokers. Finally, we tested interactions between cigarette price and bans.Results: A $1 increase in price was associated with a 3% reduction in risk of current smoking (adjusted risk ratio [aRR]: 0.97; 95% confidence interval [CI] = 0.93, 1.0), a 7% reduction in risk of heavy smoking (aRR: 0.93; CI = 0.87, 0.99), a 20% increase in risk of smoking cessation (aRR: 1.2; CI = 0.99, 1.4), and a 35% reduction in the average number of cigarettes smoked per day by heavy baseline smokers (ratio of geometric means: 0.65; CI = 0.45, 0.93). We found no association between smoking bans and outcomes, and no evidence that price effects were modified by the presence of bans.Conclusions: Results underscore the importance of local prices, but not hospitality smoking bans, in influencing older adults' smoking behaviors. [ABSTRACT FROM AUTHOR]

Associations with antihypertensive medication classes and progression of arterial stiffness have not been studied in a prospective multiethnic cohort. All participants had hypertension at baseline, defined as blood pressure ≥140/90 mm Hg or use of antihypertensive medications. Medication use and blood pressure were assessed at 5 time points. Young's elastic modulus and distensibility coefficient of the right common carotid artery were obtained by ultrasound at baseline and after a mean (SD) follow-up period of 9.4 (0.5) years. Associations with changes in Young's elastic modulus and distensibility coefficient, baseline antihypertensive medication use, number of visits each medication class was reported, and blood pressure control (<140/90 mm Hg) were assessed using multiple linear regression models. At baseline, mean age of participants (n=1206) was 63.2 (9.0) years (55% female; 35% African American, 19% Hispanic, 12% Chinese). Mean systolic blood pressure was 136.5 (20.6) mm Hg. Greater progression of arterial stiffness was associated with older age, African American ethnicity, and baseline calcium channel blocker use. There were no other associations between changes in Young's elastic modulus or distensibility coefficient and use of other medication classes (all P>0.4). Achieving blood pressure control (<140/90 mm Hg) at all visits was associated with slower progression of arterial stiffness (Young's elastic modulus: β=-790.1 mm Hg, P=0.01; distensibility coefficient: β=7.34×10-4 mm Hg-1, P=0.001). Blood pressure control, rather than use of any particular antihypertensive medication class, was associated most strongly with slowing arterial stiffness progression. Over nearly a decade of follow-up, no consistent associations between any specific antihypertensive medication class and progressive carotid arterial stiffening were identified. [ABSTRACT FROM AUTHOR]

The MESA Air (Multi-Ethnic Study of Atherosclerosis and Air Pollution) leveraged the platform of the MESA cohort into a prospective longitudinal study of relationships between air pollution and cardiovascular health. MESA Air researchers developed fine-scale, state-of-the-art air pollution exposure models for the MESA Air communities, creating individual exposure estimates for each participant. These models combine cohort-specific exposure monitoring, existing monitoring systems, and an extensive database of geographic and meteorological information. Together with extensive phenotyping in MESA—and adding participants and health measurements to the cohort—MESA Air investigated environmental exposures on a wide range of outcomes. Advances by the MESA Air team included not only a new approach to exposure modeling, but also biostatistical advances in addressing exposure measurement error and temporal confounding. The MESA Air study advanced our understanding of the impact of air pollutants on cardiovascular disease and provided a research platform for advances in environmental epidemiology. [ABSTRACT FROM AUTHOR]

Background: Reduced heart rate variability, a marker of impaired cardiac autonomic function, has been linked to short-term exposure to airborne particles. This research adds to the literature by examining associations with long-term exposures to coarse particles (PM10-2.5).Methods: Using electrocardiogram recordings from 2,780 participants (45-84 years) from three Multi-ethnic Study of Atherosclerosis sites, we assessed the standard deviation of normal to normal intervals and root-mean square differences of successive normal to normal intervals at a baseline (2000-2002) and follow-up (2010-2012) examination (mean visits/person = 1.5). Annual average concentrations of PM10-2.5 mass, copper, zinc, phosphorus, silicon, and endotoxin were estimated using site-specific spatial prediction models. We assessed associations for baseline heart rate variability and rate of change in heart rate variability over time using multivariable mixed models adjusted for time, sociodemographic, lifestyle, health, and neighborhood confounders, including copollutants.Results: In our primary models adjusted for demographic and lifestyle factors and site, PM10-2.5 mass was associated with 1.0% (95% confidence interval [CI]: -4.1, 2.1%) lower standard deviation of normal to normal interval levels per interquartile range of 2 μg/m. Stronger associations, however, were observed before site adjustment and with increasing residential stability. Similar patterns were found for root-mean square differences of successive normal to normal intervals. We found little evidence for associations with other chemical species and with the rate of change in heart rate variability, though endotoxin was associated with increasing heart rate variability over time.Conclusion: We found only weak evidence that long-term PM10-2.5 exposures are associated with lowered heart rate variability. Stronger associations among residentially stable individuals suggest that confirmatory studies are needed. [ABSTRACT FROM AUTHOR]

Background: Social factors may enhance health effects of air pollution, yet empirical support is inconsistent. The interaction of social and environmental factors may only be evident with long-term exposures and outcomes that reflect long-term disease development.Methods: We used cardiac magnetic resonance imaging data from the Multi-Ethnic Study of Atherosclerosis to assess left-ventricular mass index (LVMI) and left-ventricular ejection fraction (LVEF). We assigned residential concentrations of fine particulate matter (PM2.5), oxides of nitrogen, and nitrogen dioxide in the year 2000 to each participant in 2000 using prediction models. We examined modifying roles of four measures of adversity: race/ethnicity, racial/ethnic residential segregation, and socioeconomic status and psychosocial adversity as composite indices on the association between air pollution and LVMI or LVEF.Results: Compared with whites, blacks showed a stronger adjusted association between air pollution and LVMI. For example, for each 5 µg/m greater PM2.5 level, whites showed a 1.0 g/m greater LVMI (95% confidence interval = -1.3, 3.1), while blacks showed an additional 4.0 g/m greater LVMI (95% confidence interval = 0.3, 8.2). Results were similar for oxides of nitrogen and nitrogen dioxide with regard to black race and LVMI. However, we found no evidence of a modifying role of other social factors or ethnic groups. Furthermore, we found no evidence of a modifying role for any social factors or racial/ethnic groups on the association between air pollution and LVEF.Conclusions: Our results suggest that racial group membership may modify the association between air pollution and cardiovascular disease. [ABSTRACT FROM AUTHOR]

Background: Late‐life ambient air pollution is a novel risk factor for brain aging. Air quality improvement has been associated with improved cardiopulmonary health and reduced mortality; however, whether it is associated with reduced dementia risk is unknown. Method: We studied a geographically‐diverse cohort from the Women's Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO). Participants included 2239 older women (aged 74‐92) without dementia at WHIMS‐ECHO enrollment in 2008‐12. Incident dementia cases, based on DSM‐IV criteria, were centrally‐adjudicated annually (2008‐18). Yearly mean concentrations of ambient PM2.5 (fine particulate matter) and NO2 at residential locations were estimated using validated regionalized universal kriging models. These annual estimates were then averaged over 3‐year periods at both immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS‐ECHO enrollment. Individual‐level improved air quality was defined as reduction from remote to recent exposures. We used Cox proportional hazard models to estimate the hazard ratios (HR) for dementia risk associated with air quality measures, adjusting for sociodemographic, lifestyle, and clinical characteristics. We incorporated inverse‐probability weighting to account for differential attrition during the follow up. Models were replicated using multiple imputation to include those with missing air pollution and covariate data as sensitivity analyses. Results: We identified 398 incident dementia cases during median 6.1 years of follow up (interquartile range [IQR]=5.2 years). PM2.5 and NO2 reduced significantly over the 10 years before WHIMS‐ECHO enrollment. Greater improvement in air quality was significantly associated with reduced dementia risks (HRPM2.5=0.80 per IQR=1.78µg/m3, 95% confidence interval [CI]=[0.71, 0.91]; HRNO2=0.80 per IQR=3.91ppb, 95%CI=[0.71, 0.90]), equivalent to the lower risk observed in women 2.4 years younger at baseline. There was some evidence that recent PM2.5 exposure was associated with higher dementia risk (HRPM2.5=1.16 per IQR=2.90µg/m3, 95%CI=[0.98, 1.38]), but the lower dementia risk associated with improved air quality remained after further adjusting for the recent exposure effects. The observed associations did not substantially differ by age, education, geographic region, APOE e4 genotypes, or cardiovascular risk factors. Similar results were found in the sensitivity analyses using multiple imputation. Conclusions: Long‐term air quality improvement in late‐life was associated with lower dementia risk in older women. [ABSTRACT FROM AUTHOR]

Background: Late‐life exposure to ambient air pollution is a modifiable risk factor for dementia, but epidemiological studies have shown inconsistent evidence for cognitive decline. Improved air quality (AQ) is associated with decreased mortality and improved respiratory health, but no studies have examined the association with cognitive function. Methods: Participants included 2,232 U.S. community‐dwelling older women (aged 74‐92) from the Women's Health Initiative Memory Study‐Epidemiology of Cognitive Health Outcomes (WHIMS‐ECHO) without dementia at enrollment. Measures of annual (2008‐18) cognitive function included general cognitive status (assessed by the Telephone Interview for Cognitive Status‐modified, TICSm) and episodic memory (assessed by the telephone‐based California Verbal Learning Test, CVLT). Regionalized universal kriging models were used to estimate annual exposures (1996‐2012) to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations, which were averaged over the 3‐year periods immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS‐ECHO enrollment. Individual‐level improvements in AQ were calculated as the reduction from remote to recent exposures. We used linear mixed effect models to examine the associations between improved AQ and the rates of cognitive decline in TICSm and CVLT trajectories, adjusting for sociodemographic, lifestyle, and clinical characteristics. Results: AQ improved significantly for both PM2.5 and NO2 over the 10 years before enrollment. During a median of 6.2 (inter‐quartile‐range [IQR]=5.0) years of follow‐up, general cognitive status (βTICSm=‐0.42/year, 95% CI: ‐0.44, ‐0.40) and episodic memory (βCVLT=‐0.59/year, 95% CI: ‐0.64, ‐0.54) significantly declined. Greater AQ improvement was associated with slower decline in TICSm (βPM2.5=0.026/year per IQR=1.79 µg/m3, 95% CI: 0.001, 0.05; βNO2=0.034/year per IQR=3.92 ppb, 95% CI: 0.01, 0.06) and CVLT (βPM2.5=0.070/year per IQR=1.79 µg/m3, 95% CI: 0.02, 0.12; βNO2=0.060/year per IQR=3.97 ppb, 95% CI: 0.005, 0.12). The respective associations with TICSm and CVLT were equivalent to the slower declines found in women 0.9‐1.2 and 1.4‐1.6 years younger, and did not significantly differ by age, region, education, ApoE e4 genotypes, or cardiovascular risk factors. The benefits were attenuated after excluding incident dementia cases but remained after excluding prevalent or incident stroke cases. Conclusions: Long‐term improvement in AQ in late‐life was associated with slower cognitive declines in older women. [ABSTRACT FROM AUTHOR]

Background: Evidence linking long‐term air pollutant exposures with dementia‐related risks is increasing. Changes in the brain may occur decades before diagnosis, and studies assessing the effects of air pollution on dementia should account for participant residential history to reduce exposure misclassification. Using the Ginkgo Evaluation of Memory Study (GEMS), we evaluated cumulative PM2.5 and NO2 exposure on dementia risk both with and without historical residential addresses. Method: GEMS was a randomized trial of 3,069 participants in Hagerstown MD, Pittsburgh PA, Sacramento CA, and Winston‐Salem NC from 2000‐2008. Residential historical addresses were obtained through LexisNexis, a company constructing address histories from public databases. PM2.5 (1980‐1999) and NO2 (1990‐1999) cumulative exposures were calculated for each participant from a spatio‐temporal model in two ways: 1) using residential address histories reconstructed from LexisNexis addresses from 1980‐1999 (Figure 1), and 2) assuming participants lived from 1980‐1999 at the address documented during the GEMS baseline visit (2000‐2002). Hazard ratios from Cox models of all‐cause dementia, Alzheimer's disease (AD), and mixed vascular dementia (VaD/AD) were compared across both sets of cumulative PM2.5 and NO2 estimates. Models were adjusted for age, study site, randomization year, gender, treatment group, neighborhood deprivation index (NDI), education, smoking status, smoking pack years, passive smoking exposure and apolipoprotein E4 (APOE4) status. Result: Hazard ratios based on the LexisNexis historical addresses were generally larger than those from analyses without residential histories (Figure 2). The largest attenuation in effect after eliminating address history was for participants with vascular dementia either with or without AD (VaD/AD). An approximate interquartile range (IQR; 3 µg/m3) increase in 10 year mean NO2 exposure was associated with a 39% (95% CI: 7%, 81%) greater risk of mixed VaD/AD, but this decreased to 25% (95% CI: ‐7%, 66%) without histories. Similarly, an IQR (2 µg/m3) increase in 20 year PM2.5 was associated with a 19% (95% CI: 4%, 36%) greater risk of all cause dementia compared to 14% (95% CI:‐1%, 31%) without the historical addresses. Conclusion: For epidemiological studies aiming to quantify long term place‐based exposures related to dementia risk, utilizing residential address databases may reduce misclassification in exposure assignments. [ABSTRACT FROM AUTHOR]

Background: Animal studies suggest associations between exposure to air pollutants and increased amyloid beta (Aβ) pathology. However, there is limited research evaluating the relationship of air pollution to Aβ levels in human populations. Therefore, this study examined the role of long‐term air pollution exposure in plasma amyloid levels in a US cohort of older adults. Method: This cross‐sectional study included participants from the Ginkgo Evaluation of Memory Study, a longitudinal cohort of older adults (aged 75 years and older) recruited from four US communities who were dementia free at baseline. Plasma Aβ1‐40 levels were measured in 2000‐2002 and again in 2007‐2008 and log transformed for analyses. We applied validated fine‐scale spatiotemporal models to estimate fine particulate matter (PM2.5), coarse particles (PM10) and nitrogen dioxide (NO2) at participant residential addresses. Address history was constructed up to 20 years prior to visit dates using LexisNexis, a commercial credit reporting company. Exposure to air pollutants was averaged over multiple time periods (from one to 20 years) prior to plasma collection. We estimated percent differences (95% CIs) from ordinary least squares and linear mixed‐effect regression models for baseline and repeated measures data, respectively. All models were adjusted for age, race, gender, site, education, treatment, cystatin c, neighborhood deprivation index, alcohol intake, smoking status, pack‐years of smoking, passive smoke exposure and gait speed. Result: This study included 3,029 participants with measured Aβ1‐40. A 3 µg/m3 (interquartile range (IQR)) higher PM10 over 10 years was associated with higher levels of Aβ1‐40 at baseline: percent difference 1.80% (95% CI: 0.22%, 3.40%). We also observed a positive association of increased magnitude in repeated measures analyses: percent difference 5.20% (95% CI: 3.69%, 6.72%). Similar associations between PM2.5 (IQR = 2 µg/m3) and NO2 (IQR = 7 ppb) and Aβ1‐40 were found in repeated measures analyses. Findings from other pollutants and exposure periods are presented in Figure 1. Conclusion: These findings provide some of the first epidemiologic evidence suggesting long‐term concentrations of PM2.5, PM10 and NO2 are associated with increased Aβ1‐40. [ABSTRACT FROM AUTHOR]

Background: Air pollution is associated with cardiovascular disease, and systemic inflammation may mediate this effect. We assessed associations between long- and short-term concentrations of air pollution and markers of inflammation, coagulation, and endothelial activation.Methods: We studied participants from the Multi-Ethnic Study of Atherosclerosis from 2000 to 2012 with repeat measures of serum C-reactive protein (CRP), interleukin-6 (IL-6), fibrinogen, D-dimer, soluble E-selectin, and soluble Intercellular Adhesion Molecule-1. Annual average concentrations of ambient fine particulate matter (PM2.5), individual-level ambient PM2.5 (integrating indoor concentrations and time-location data), oxides of nitrogen (NOx), nitrogen dioxide (NO2), and black carbon were evaluated. Short-term concentrations of PM2.5 reflected the day of blood draw, day prior, and averages of prior 2-, 3-, 4-, and 5-day periods. Random-effects models were used for long-term exposures and fixed effects for short-term exposures. The sample size was between 9,000 and 10,000 observations for CRP, IL-6, fibrinogen, and D-dimer; approximately 2,100 for E-selectin; and 3,300 for soluble Intercellular Adhesion Molecule-1.Results: After controlling for confounders, 5 µg/m increase in long-term ambient PM2.5 was associated with 6% higher IL-6 (95% confidence interval = 2%, 9%), and 40 parts per billion increase in long-term NOx was associated with 7% (95% confidence interval = 2%, 13%) higher level of D-dimer. PM2.5 measured at day of blood draw was associated with CRP, fibrinogen, and E-selectin. There were no other positive associations between blood markers and short- or long-term air pollution.Conclusions: These data are consistent with the hypothesis that long-term exposure to air pollution is related to some markers of inflammation and fibrinolysis. [ABSTRACT FROM AUTHOR]