2014 Progress Report: Cognitive Decline, Cardiovascular Changes, and Biological Aging in Response to Air Pollution

EPA Grant Number: R834798C002
Subproject: this is subproject number 002 , established and managed by the Center Director under grant R834798
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).

Center: Air Pollution Mixtures: Health Effects across Life Stages
Center Director: Koutrakis, Petros
Title: Cognitive Decline, Cardiovascular Changes, and Biological Aging in Response to Air Pollution
Investigators: Schwartz, Joel , Mittleman, Murray
Institution: Harvard University
EPA Project Officer: Ilacqua, Vito
Project Period: January 1, 2011 through December 31, 2015 (Extended to December 31, 2016)
Project Period Covered by this Report: January 1, 2014 through December 31,2014
RFA: Clean Air Research Centers (2009) RFA Text |  Recipients Lists
Research Category: Health Effects , Air

Objective:

In this Project we investigate the acute and chronic effects of air pollution on cognitive and neurological impairments, systemic inflammation, and vascular dysfunction in the Normative Aging Study (NAS) cohort. We examine how these effects differ depending on the composition of multi-pollutant mixtures and the source contributions to PM composition. Also we ascertain the level of increased effects in susceptible and vulnerable subpopulations by examining modifying factors of obesity, diabetes, diet, socioeconomic position, and psychosocial stress.

Progress Summary:

We have continued to make good progress on the specific aims of the project with our NAS cohort studies as well as with our updated Black Carbon (BC) and satellite based exposure models, which are presented below. Our annual progress summary is grouped into three sections, including: results of studies using central site modeling; results of studies using spatiotemporal modeling, and; analytical advances.

Results using Central Site Monitoring: In Mehta et al. (2014) we reported that short-term exposures to air pollution (specifically PM2.5, sulfate, and particle count concentration) in the Normative Aging Study were associated with augmentation index and augmentation pressure, correlates of arterial stiffness.  These findings support a role for vascular function in the cardiovascular health effects associated with air pollution.

In Lepeule et al. (2014) we evaluated the lag structure of air pollutant associations with lung function and potential effect modification by DNA methylation at 26 CpG sites in 9 candidate genes in the NAS population.  In this study, we found that interquartile range increases in subchronic (but not acute) exposure to black carbon, total and non-traffic PM2.5, and traffic related gases were associated with a decrease in forced vital capacity and forced expiratory volume in 1 second.  Non traffic related pollutants had weaker associations.  Furthermore, associations were more pronounced in participants with low methylation in TLR2 and high methylation in GCR genes. The findings indicate that DNA methylation may modify the effects of traffic-related pollutants via epigenetic mechanisms related to inflammation and immunity.

In Fossati et al. (2014) we investigated the association of exposure to ambient particles, black carbon, organic carbon, and sulfates with blood leukocyte expression changes in 14 microRNAs, considering several different time windows.  We found the strongest associations for the 7-day moving averages of PM2.5 and BC, and the 48-hour OC. The association with sulfate was stable across time windows.  Results show that down-regulation of microRNAs involved in processes related to PM exposure could be caused by exposure to ambient particles, particularly those which are traffic-related.  Polymorphisms in microRNA-related genes GEMIN4 and DGCR8 may modify effects of exposure.

In Bind et al. (2014a), we found that ambient temperature and relative humidity are related to methylation of long interspersed nuclear elements (LINE-1), Alu, and 9 candidate genes controlling coagulation, inflammation, cortisol, DNA repair, and metabolic pathway.  DNA methylation in blood cells may reflect biological effects of temperature and relative humidity.  Temperature and relative humidity may interact to produce stronger effects.  In addition, results of this study also indicate there may be a potential health effect of relative humidity independent of temperature.

In Link (2013) we showed that exposure to PM2.5 was associated with increased odds of atrial fibrillation (AF) within hours of exposure in patients with known cardiac disease. As an acute trigger of AF, air pollution likely contributes to the pollution-associated adverse cardiac outcomes observed in epidemiological studies.

Results using spatiotemporal exposure models: In Kloog (2013) we combined our Spatiotemporal AOD-LUR PM2.5 model with individual mortality data in Massachusetts geocoded to home address, and showed associations with both long- and short-term exposure. Unlike most cohort studies, which have samples highly unrepresentative of the general population, these results are for the entire population of Massachusetts. For short-term exposure, we found that for every 10-μg/m3 increase in PM2.5 exposure there was a 2.8% increase in PM-related mortality (95% confidence interval (CI) = 2.0–3.5). For the long-term exposure at the grid cell level, we found a Rate Ratio (RR) for every 10-μg/m3 increase of 1.6 (CI = 1.5–1.8) for particle-related diseases. Local PM2.5 had an RR of 1.4 (CI = 1.3–1.5), which was independent of and additive to the grid cell effect.

In Zanobetti et al. (2014) we used spatiotemporal modeling to assess exposure to black carbon (BC) and PM2.5 to investigate the association of exposure with arrhythmia episodes in the Normative Aging Study.  We found that BC and PM2.5 exposures, averaged over the 3 days prior to health assessment, were associated with increases in the odds of having a ventricular ectopy episode.  Risks were higher for obese patients and those with genetic susceptibility, demonstrating that increased levels of short-term traffic-related pollutants may increase the risk of ventricular arrhythmia in elderly subjects.

In Kloog et al. (2014) we applied our prediction models that incorporate satellite AOD date to assess PM2.5 exposures in the mid-Atlantic States and combined the resulting exposure estimates with hospital admittance data to investigate the short term effects of PM2.5 exposure on hospital admissions of the elderly population.  In this study, we observed associations with PM exposure and hospitalization for all outcomes examined, and found differences in risk for CVD admissions between people living in urban and rural areas.  This study demonstrated that our AOD-based exposure models can be successfully applied to epidemiological studies investigating the health effects of short term exposures to PM2.5.

In Colcino et al. (2014) we used our spatiotemporal BC exposure model to study the association of BC with cognitive function in the Normative Aging Study.  We found that MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects.  We used mitochondrial haplotyping to identify nine haplogroups which were phylogenetically categorized in four clusters. We found that the association of BC with impaired cognition was worsened in carriers of phylogenetically-related mtDNA haplogroups in Cluster 4. No BC effects were detected in Cluster 2 and 3 carriers.

In Chudnovsky et al. (2013) we showed that high-resolution satellite retrieval data could be used to develop models suitable to generate 1 x 1 km PM2.5 exposure data of sufficient quality for use in epidemiological studies. The model showed excellent correlation with measured concentrations (out of sample R2=0.89), and high accuracy for the cities of Boston and New Haven.  Furthermore, the model captured the pollution levels along the highways and many urban areas, extending our ability to investigate spatial patterns of urban air quality, such as examining exposures within areas of high traffic.

Advances in analytical methods:  During the past year, we have published papers that utilize novel analytical methodology in the investigation of exposure-related health effects in the Normative Aging Study.  In Bind et al. (2014b), we applied mediation analysis to investigate whether air pollution exposures were related to methylation on genes related to two different pathways, coagulation and inflammation.  We examined whether the association between exposure and gene-specific methylation varied by participant characteristics; we also investigated whether the association between exposure and cardiovascular biomarkers was mediated via change in gene-specific methylation. 

In Bind et al. (2014c) we developed a new pathway analysis approach to investigate whether gene variants within relevant pathways (e.g., oxidative stress, endothelial function, and metal processing) modified the association between particulate air pollution exposures and fibrinogen, C-reactive protein (CRP), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1).  To investigate the role of biological mechanisms, while reducing the number of comparisons in the analysis, we created pathway-specific scores using gene variants related to each pathway.  Appropriate gene variants were selected using the least absolute shrinkage and selections operator (LASSO) to relate independent outcomes representative of each pathway to gene variants.  The resulting two-stage penalization method is easy to implement and can be used for large-scale genetic applications.

Future Activities:

We will continue our work on exploring multi-pollutant mixtures by examining the effect of metals, EC, and OC in a national study of cities with speciation data. This also will include meta-analyses to examine effect modification by temperature and other city characteristics. We will apply our cluster analyses, and our daily XRF data, and look at health effects of clusters and metals in the NAS, and we will expand our examination of pollution effects on DNA methylation, using the Illumina 450k array. We will further refine our PM2.5 model using 1km MAIAC data and apply it to the NAS and other cohorts.


Journal Articles on this Report : 38 Displayed | Download in RIS Format

Other subproject views: All 87 publications 87 publications in selected types All 87 journal articles
Other center views: All 410 publications 347 publications in selected types All 347 journal articles
Type Citation Sub Project Document Sources
Journal Article Bind M-A, Zanobetti A, Gasparrini A, Peters A, Coull B, Baccarelli A, Tarantini L, Koutrakis P, Vokonas P, Schwartz J. Effects of temperature and relative humidity on DNA methylation. Epidemiology 2014;25(4):561-569. R834798 (2014)
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  • Journal Article Bind M-A, Baccarelli A, Zanobetti A, Tarantini L, Suh H, Vokonas P, Schwartz J. Air pollution and markers of coagulation, inflammation, and endothelial function:associations and epigene-environment interactions in an elderly cohort. Epidemiology 2012;23(2):332-340. R834798 (2012)
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  • Journal Article Bind M-A, Coull B, Suh H, Wright R, Baccarelli A, Vokonas P, Schwartz J. A novel genetic score approach using instruments to investigate interactions between pathways and environment: application to air pollution. PLoS One 2014;9(4):e96000 (8 pp.). R834798 (2014)
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  • Journal Article Bind M-A, Lepeule J, Zanobetti A, Gasparrini A, Baccarelli A, Coull BA, Tarantini L, Vokonas PS, Koutrakis P, Schwartz J. Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis. Epigenetics 2014;9(3):448-458. R834798 (2014)
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  • Journal Article Chiu Y-HM, Coull BA, Sternthal MJ, Kloog I, Schwartz J, Cohen S, Wright RJ. Effects of prenatal community violence and ambient air pollution on childhood wheeze in an urban population.Journal of Allergy and Clinical Immunology 2014;133(3):713-722.e4. R834798 (Final)
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  • Journal Article Chudnovsky AA, Koutrakis P, Kloog I, Melly S, Nordio F, Lyapustin A, Wang Y, Schwartz J. Fine particulate matter predictions using high resolution Aerosol Optical Depth (AOD) retrievals. Atmospheric Environment 2014;89:189-198. R834798 (2014)
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  • Journal Article Colicino E, Power MC, Cox DG, Weisskopf MG, Hou L, Alexeeff SE, Sanchez-Guerra M, Vokonas P, Spiro III A, Schwartz J, Baccarelli AA. Mitochondrial haplogroups modify the effect of black carbon on age‐related cognitive impairment. Environmental Health 2014;13(1):42. R834798 (Final)
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  • Journal Article Dai L, Zanobetti A, Koutrakis P, Schwartz JD. Associations of fine particulate matter species with mortality in the United States: a multicity time-series analysis. Environmental Health Perspectives 2014;122(8):837-842. R834798 (2014)
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  • Journal Article Fang SC, Schwartz J, Yang M, Yaggi HK, Bliwise DL, Araujo AB. Traffic‐related air pollution and sleep in the Boston Area Community Health Survey. Journal of Exposure Science & Environmental Epidemiology 2015;25(5):451-456. R834798 (Final)
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  • Journal Article Fossati S, Baccarelli A, Zanobetti A, Hoxha M, Vokonas PS, Wright RO, Schwartz J. Ambient particulate air pollution and MicroRNAs in elderly men. Epidemiology 2014;25(1):68-78. R834798 (2014)
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  • Journal Article Kloog I, Koutrakis P, Coull BA, Lee HJ, Schwartz J. Assessing temporally and spatially resolved PM2.5 exposures for epidemiological studies using satellite aerosol optical depth measurements. Atmospheric Environment 2011;45(35):6267-6275. R834798 (2012)
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  • Journal Article Kloog I, Coull BA, Zanobetti A, Koutrakis P, Schwartz JD. Acute and chronic effects of particles on hospital admissions in New-England. PLoS ONE 2012;7(4):e34664 (8 pp.). R834798 (2012)
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  • Journal Article Kloog I, Melly SJ, Ridgway WL, Coull BA, Schwartz J. Using new satellite based exposure methods to study the association between pregnancy PM2.5 exposure, premature birth and birth weight in Massachusetts. Environmental Health 2012;11:40 (8 pp.). R834798 (2012)
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  • Journal Article Kloog I, Nordio F, Coull BA, Schwartz J. Incorporating local land use regression and satellite aerosol optical depth in a hybrid model of spatiotemporal PM2.5 exposures in the Mid-Atlantic states. Environmental Science & Technology 2012;46(21):11913-11921. R834798 (2013)
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  • Journal Article Kloog I, Ridgway B, Koutrakis P, Coull BA, Schwartz JD. Long- and short-term exposure to PM2.5 and mortality: using novel exposure models. Epidemiology 2013;24(4):555-561. R834798 (2013)
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  • Journal Article Kloog I, Nordio F, Zanobetti A, Coull BA, Koutrakis P, Schwartz JD. Short term effects of particle exposure on hospital admissions in the Mid-Atlantic states:a population estimate. PLoS ONE 2014;9(2):e88578 (7 pp.). R834798 (2014)
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  • Journal Article Lepeule J, Laden F, Dockery D, Schwartz J. Chronic exposure to fine particles and mortality: an extended follow-up of the Harvard Six Cities study from 1974 to 2009. Environmental Health Perspectives 2012;120(7):965-970. R834798 (2012)
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  • Journal Article Lepeule J, Baccarelli A, Tarantini L, Motta V, Cantone L, Litonjua AA, Sparrow D, Vokonas PS, Schwartz J. Gene promoter methylation is associated with lung function in the elderly:the Normative Aging Study. Epigenetics 2012;7(3):261-269. R834798 (2012)
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  • Journal Article Lepeule J, Bind M-AC, Baccarelli AA, Koutrakis P, Tarantini L, Litonjua A, Sparrow D, Vokonas P, Schwartz JD. Epigenetic influences on associations between air pollutants and lung function in elderly men: the Normative Aging Study. Environmental Health Perspectives 2014;122(6):566-572. R834798 (2014)
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  • Journal Article Link MS, Luttmann-Gibson H, Schwartz J, Mittleman MA, Wessler B, Gold DR, Dockery DW, Laden F. Acute exposure to air pollution triggers atrial fibrillation. Journal of the American College of Cardiology 2013;62(9):816-825. R834798 (2013)
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  • Journal Article Madrigano J, Kloog I, Goldberg R, Coull BA, Mittleman MA, Schwartz J. Long-term exposure to PM2.5 and incidence of acute myocardial infarction. Environmental Health Perspectives 2013;121(2):192-196. R834798 (2013)
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  • Journal Article Mehta AJ, Zanobetti A, Koutrakis P, Mittleman MA, Sparrow D, Vokonas P, Schwartz J. Associations between short-term changes in air pollution and correlates of arterial stiffness: the Veterans Affairs Normative Aging Study, 2007-2011. American Journal of Epidemiology 2014;179(2):192-199. R834798 (2014)
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  • Journal Article Nordio F, Kloog I, Coull BA, Chudnovsky A, Grillo P, Bertazzi PA, Baccarelli AA, Schwartz J. Estimating spatio-temporal resolved PM10 aerosol mass concentrations using MODIS satellite data and land use regression over Lombardy, Italy. Atmospheric Environment 2013;74:227-236. R834798 (2013)
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  • Journal Article Peters JL, Kubzansky LD, Ikeda A, Spiro III A, Wright RO, Weisskopf MG, Kim D, Sparrow D, Nie LH, Hu H, Schwartz J. Childhood and adult socioeconomic position, cumulative lead levels, and pessimism in later life: the VA Normative Aging Study. American Journal of Epidemiology 2011;174(12):1345-1353. R834798 (2010)
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  • Journal Article Power, MC, Weisskopf MG, Alexeef SE, Coull BA, Spiro III A , Schwartz J. Traffic-related air pollution and cognitive function in a cohort of older men. Environmental Health Perspectives 2011;119(5):682-687. R834798 (2010)
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  • Journal Article Power MC, Weisskopf MG, Alexeeff SE, Wright RO, Coull BA, Spiro III A, Schwartz J. Modification by hemochromatosis gene polymorphisms of the association between traffic-related air pollution and cognition in older men: a cohort study. Environmental Health 2013;12:16 (8 pp.). R834798 (2014)
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  • Journal Article Schwartz J, Alexeeff SE, Mordukhovich I, Gryparis A, Vokonas P, Suh H, Coull BA. Association between long-term exposure to traffic particles and blood pressure in the Veterans Administration Normative Aging Study. Occupational and Environmental Medicine 2012;69(6):422-427. R834798 (2012)
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  • Journal Article Sivagangabalan G, Spears D, Masse S, Urch B, Brook RD, Silverman F, Gold DR, Lukic KZ, Speck M, Kusha M, Farid T, Poku K, Shi E, Floras J, Nanthakumar K. The effect of air pollution on spatial dispersion of myocardial repolarization in healthy human volunteers. Journal of the American College of Cardiology 2011;57(2):198-206. R834798 (2012)
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  • Journal Article Sofer T, Maity A, Coull B, Baccarelli A, Schwartz J, Lin X. Multivariate gene selection and testing in studying the exposure effects on a gene set. Statistics in Bioscience 2012;4(2):319-338. R834798 (2013)
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  • Journal Article Sofer T, Baccarelli A, Cantone L, Coull B, Maity A, Lin X, Schwartz J. Exposure to airborne particulate matter is associated with methylation pattern in the asthma pathway. Epigenomics 2013;5(2):147-154. R834798 (2013)
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  • Journal Article Valdes A, Zanobetti A, Halonen JI, Cifuentes L, Morata D, Schwartz J. Elemental concentrations of ambient particles and cause specific mortality in Santiago, Chile: a time series study. Environmental Health 2012;11:82 (8 pp.). R834798 (2014)
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  • Journal Article von Klot S, Zanobetti A, Schwartz J. Influenza epidemics, seasonality, and the effects of cold weather on cardiac mortality. Environmental Health 2012;11:74. R834798 (2013)
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  • Journal Article Wang Y, Eliot MN, Koutrakis P, Gryparis A, Schwartz JD, Coull BA, Mittleman MA, Milberg WP, Lipsitz LA, Wellenius GA. Ambient air pollution and depressive symptoms in older adults: results from the MOBILIZE Boston Study. Environmental Health Perspectives 2014;122(6):553-558. R834798 (Final)
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  • Journal Article Wang Y, Eliot MN, Kuchel GA, Schwartz J, Coull BA, Mittleman MA, Lipsitz LA, Wellenius GA. Long-term exposure to ambient air pollution and serum leptin in older adults: results from the MOBILIZE Boston Study. Journal of Occupational and Environmental Medicine 2014;56(9):e73-e77. R834798 (Final)
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  • Journal Article Wilker EH, Mittleman MA, Coull BA, Gryparis A, Bots ML, Schwartz J, Sparrow D. Long-term exposure to black carbon and carotid intima-media thickness: the Normative Aging Study. Environmental Health Perspectives 2013;121(9):1061-1067. R834798 (2013)
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  • Journal Article Zanobetti A, Schwartz J. Ozone and survival in four cohorts with potentially predisposing diseases. American Journal of Respiratory and Critical Care Medicine 2011;184(7):836-841. R834798 (2010)
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  • Journal Article Zanobetti A, O'Neill MS, Gronlund CJ, Schwartz JD. Summer temperature variability and long-term survival among elderly people with chronic disease. Proceedings of the National Academy of Sciences of the United States of America 2012;109(17):6608-6613. R834798 (2012)
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  • Journal Article Zanobetti A, Coull BA, Gryparis A, Kloog I, Sparrow D, Vokonas PS, Wright RO, Gold DR, Schwartz J. Associations between arrhythmia episodes and temporally and spatially resolved black carbon and particulate matter in elderly patients. Occupational and Environmental Medicine 2014;71(3):201-207. R834798 (2014)
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  • Supplemental Keywords:

    Scientific Discipline, Air, air toxics, Health Risk Assessment, Air Pollution Effects, Biochemistry, Environmental Monitoring, Biology, ambient air quality, children's health, complex mixtures, health effects, particulates, sensitive populations, air pollutants, aerosol particles, biological sensitivities, exposure and effects, lung epithelial cells, susceptible populations, chemical composition, neurotoxicity, human exposure, toxicity, coronary artery disease, cardiopulmonary, cardiotoxicity, environmental effects, human health, mortality

    Progress and Final Reports:

    Original Abstract
  • 2010 Progress Report
  • 2011 Progress Report
  • 2012 Progress Report
  • 2013 Progress Report
  • Final Report

  • Main Center Abstract and Reports:

    R834798    Air Pollution Mixtures: Health Effects across Life Stages

    Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
    R834798C001 Relative Toxicity of Air Pollution Mixtures
    R834798C002 Cognitive Decline, Cardiovascular Changes, and Biological Aging in Response to Air Pollution
    R834798C003 Identifying the Cognitive and Vascular Effects of Air Pollution Sources and Mixtures in the Framingharn Offspring and Third Generation Cohorts
    R834798C004 Longitudinal Effects of Multiple Pollutants on Child Growth, Blood Pressure and Cognition
    R834798C005 A National Study to Assess Susceptibility, Vulnerability, and Effect Modification of Air Pollution Health Risks