Persistent Organic Pollutants and Mortality in the United States, NHANES 1999-2011.

Background Persistent organic pollutants (POPs) are environmentally and biologically persistent chemicals that include polybrominated diphenyl ethers (PBDEs), per- and polyfluoroalkyl substances (PFASs), polychlorinated biphenyls (PCBs), and organochlorine (OC) pesticides. Currently, data on the associations between exposure to POPs and the risk of mortality in the U.S. population is limited. Our objective was to determine if higher exposure to POPs is associated with greater risk of all-cause, cancer, heart/cerebrovascular disease, or other-cause mortality. Methods Analyses included participants aged 60 years and older from the 1999–2006 National Health and Nutrition Examination Surveys (NHANES). We included 483 participants for analyses of PBDEs, 1043 for PFASs, and 461 for PCBs, and 1428 for OC pesticides. Exposures to POPs were estimated using biomarkers measured in serum. Mortality status through December 31, 2011 was obtained from public-use, linked mortality files. We used Cox proportional hazard models to quantify the associations of interest. Where we observed an association, we explored effect modification by sex, body mass index, smoking status, and albuminuria. We also explored the combined effect of PBDEs and OC pesticides in the subsample of participants with measures of both analytes. Results Serum measurements of PBDEs, PFASs, and PCBs were not clearly associated with increased all-cause or cause-specific mortality in older Americans. Beta-hexachlorocyclohexane was associated with an increased risk of all-cause mortality [HR per 1 SD increase =1.18, 95% CI = 1.01, 1.38]. Oxychlordane [HR = 1.15 95% CI 1.06, 1.25], p,p’-DDE [HR = 1.12, 95% CI = 1.02, 1.23], trans-nonachlor [HR = 1.11, 95% CI = 1.04, 1.18], and beta-hexachlorocyclohexane [HR = 1.25, 95% CI = 1.03, 1.52] were associated with increased risk of other-cause mortality. Exploratory analyses suggested associations between OC pesticides and other-cause mortality were modified by sex. Exploratory analyses also suggested that the combination of high PBDE and high OC pesticide exposure had a stronger than expected adverse effect on all-cause mortality. Conclusion Higher exposure to beta-hexachlorocyclohexane, an OC pesticide, is associated with increased all-cause mortality and higher exposure to four OC pesticides is associated with increased non-cancer, non-heart/cerebrovascular disease mortality in U.S. adults 60 years or older. These associations may be modified by sex or exposure to other POPs

Comparison of existing methods for algorithmic classification of dementia in the Health and Retirement Study

Background: Dementia ascertainment is difficult and costly, hindering the use of large, representative studies such as the Health and Retirement Study (HRS) to monitor trends or disparities in dementia. To address this issue, multiple groups of researchers have developed algorithms to classify dementia status in HRS participants using data from HRS and the Aging, Demographics, and Memory Study (ADAMS), an HRS sub-study that systematically ascertained dementia status. However, the relative performance of each algorithm has not been systematically evaluated. Objective: To compare the performance of five existing algorithms, overall and by sociodemographic subgroups. Methods: We created two standardized datasets: (a) training data (N=786, i.e. ADAMS Wave A and corresponding HRS data, which was used previously to create the algorithms) and (b) validation data (N=530, i.e. ADAMS Waves B, C, and D and corresponding HRS data which was not used previously to create the algorithms). In both, we used each algorithm to classify HRS participants as demented or not demented and compared the algorithmic diagnoses to the ADAMS diagnoses. Results: In the training data, overall classification accuracies ranged from 80% to 87%, sensitivity ranged from 53% to 90%, and specificity ranged from 79% to 96% across the five algorithms. Though overall classification accuracy was similar in the validation data (range: 79% to 88%), sensitivity was much lower (range: 17% to 61%), while specificity was higher (range: 82% to 98%) compared to the training data. Classification accuracy was generally worse in non-Hispanic blacks (range: 68% to 85%) and Hispanics (range: 65% to 88%), compared to non-Hispanic whites (range: 79% to 88%). Across datasets, sensitivity was generally higher for proxy-respondents, while specificity (and overall accuracy) was higher for self-respondents. Conclusions: Worse sensitivity in the validation dataset may suggest either overfitting or that the algorithms are better at identifying prevalent versus incident dementia, while differences in performance across algorithms suggest that the usefulness of each will vary depending on the user’s purpose. Further planned work will evaluate algorithm performance in external validation datasets

Biased Exposure–Health Effect Estimates from Selection in Cohort Studies: Are Environmental Studies at Particular Risk?

Background: The process of creating a cohort or cohort substudy may induce misleading exposure–health effect associations through collider stratification bias (i.e., selection bias) or bias due to conditioning on an intermediate. Studies of environmental risk factors may be at particular risk. Objectives: We aimed to demonstrate how such biases of the exposure–health effect association arise and how one may mitigate them. Methods: We used directed acyclic graphs and the example of bone lead and mortality (all-cause, cardiovascular, and ischemic heart disease) among 835 white men in the Normative Aging Study (NAS) to illustrate potential bias related to recruitment into the NAS and the bone lead substudy. We then applied methods (adjustment, restriction, and inverse probability of attrition weighting) to mitigate these biases in analyses using Cox proportional hazards models to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Analyses adjusted for age at bone lead measurement, smoking, and education among all men found HRs (95% CI) for the highest versus lowest tertile of patella lead of 1.34 (0.90, 2.00), 1.46 (0.86, 2.48), and 2.01 (0.86, 4.68) for all-cause, cardiovascular, and ischemic heart disease mortality, respectively. After applying methods to mitigate the biases, the HR (95% CI) among the 637 men analyzed were 1.86 (1.12, 3.09), 2.47 (1.23, 4.96), and 5.20 (1.61, 16.8), respectively. Conclusions: Careful attention to the underlying structure of the observed data is critical to identifying potential biases and methods to mitigate them. Understanding factors that influence initial study participation and study loss to follow-up is critical. Recruitment of population-based samples and enrolling participants at a younger age, before the potential onset of exposure-related health effects, can help reduce these potential pitfalls. Citation Weisskopf MG, Sparrow D, Hu H, Power MC. 2015. Biased exposure–health effect estimates from selection in cohort studies: are environmental studies at particular risk? Environ Health Perspect 123:1113–1122; http://dx.doi.org/10.1289/ehp.140888

Modification by hemochromatosis gene polymorphisms of the association between traffic-related air pollution and cognition in older men: a cohort study

Background: Previous studies found effect modification of associations between traffic-related air pollution and cardiovascular outcomes by polymorphisms in the hemochromatosis gene (HFE). As traffic-related air pollution may impact cognition through effects on cardiovascular health or through mechanisms which may also influence cardiovascular outcomes, we hypothesized that HFE polymorphisms would also modify a previously observed association between traffic-related air pollution exposure and cognition in older men. Methods: We considered data from 628 participants of the VA Normative Aging Study. We estimated long term exposure to black carbon (BC), a marker of traffic related air pollution, using a spatio-temporal land use regression model. We assessed cognition using the Mini-Mental State Examination (MMSE), a test of global function, and performance on a battery of other tests, covering a wide range of domains. We investigated whether variants of HFE C282Y and H63D modified the association between BC and having a low MMSE score using logistic models with generalized estimating equations and multiplicative interaction terms. Similarly, we assessed whether HFE variants modified the association between BC and performance on the cognitive battery using linear mixed models with multiplicative interaction terms. Results: Our results suggest modification of the BC-cognition association by HFE C282Y, although the test of interaction did not achieve statistical significance. In multivariable-adjusted models, participants who lacked a HFE C282Y variant (CC) exhibited an adverse association between BC and total cognition z-score (beta for a doubling in BC concentration: -0.061, 95% CI: -0.115, -0.007), while we did not observe an association in participants with at least one variant genotype (CY or YY) (beta for a doubling in BC concentration: 0.073, 95% CI: -0.081, 0.228; p-value for interaction: 0.11). The pattern of association was similar for analyses considering performance on the Mini-Mental State Examination. There was little evidence to support effect modification of the BC-cognition association by the HFE H63D genotype. Conclusions: Our data suggest that older adults who lack an HFE C282Y variant may be more susceptible to an adverse effect of traffic-related air pollution exposure on cognition. This finding and the proposed biological mechanism require confirmation

Influence of providers and nurses on completion of non-targeted HIV screening in an urgent care setting

Introduction: Despite recommendations by the Centers for Disease Control (CDC) that all adults be offered non-targeted HIV screening in all care settings, screening in acute-care settings remains unacceptably low. We performed an observational study to evaluate an HIV screening pilot in an academic-community partnership health center urgent care clinic. Methods: We collected visit data via encounter forms and demographic and laboratory data from electronic medical records. A post-pilot survey of perceptions of HIV screening was administered to providers and nurses. Multivariable analysis was used to identify factors associated with completion of testing. Results: Visit provider and triage nurse were highly associated with both acceptance of screening and completion of testing, as were younger age, male gender, and race/ethnicity. 23.5% of patients completed tests, although 36.0% requested screening; time constraints as well as risk perceptions by both the provider and patient were cited as limiting completion of screening. Post-pilot surveys showed mixed support for ongoing HIV screening in this setting by providers and little support by nurses. Conclusions: Visit provider and triage nurse were strongly associated with acceptance of testing, which may reflect variable opinions of HIV screening in this setting by clinical staff. Among patients accepting screening, visit provider remained strongly associated with completion of testing. Despite longstanding recommendations for non-targeted HIV screening, further changes to improve the testing and results process, as well as provider education and buy-in, are needed to improve screening rates

APOE ε4 Allele Modifies the Association of Lead Exposure with Age-related Cognitive Decline in Older Individuals

BACKGROUND: Continuing chronic and sporadic high-level of lead exposure in some regions in the U.S. has directed public attention to the effects of lead on human health. Long-term lead exposure has been associated with faster cognitive decline in older individuals; however, genetic susceptibility to lead-related cognitive decline during aging has been poorly studied. METHODS: We determined the interaction of APOE-epsilon variants and environmental lead exposure in relation to age-related cognitive decline. We measured tibia bone lead by K-shell-x-ray fluorescence, APOE-epsilon variants by multiplex PCR and global cognitive z-scores in 489 men from the VA-Normative Aging Study. To determine global cognitive z-scores we incorporated multiple cognitive assessments, including word list memory task, digit span backwards, verbal fluency test, sum of drawings, and pattern comparison task, which were assessed at multiple visits. We used linear mixed-effect models with random intercepts for individual and for cognitive test. RESULTS: An interquartile range (IQR:14.23μg/g) increase in tibia lead concentration was associated with a 0.06 (95% confidence interval [95%CI]: -0.11 to -0.01) lower global cognition z-score. In the presence of both ε4 alleles, one IQR increase in tibia lead was associated with 0.57 (95%CI: -0.97 to -0.16; p-value for interaction: 0.03) lower total cognition z-score. A borderline association was observed in presence of one ε4 allele (Estimate-effect per 1-IQR increase: -0.11, 95%CI: -0.22, 0.01) as well as lack of association in individuals without APOE ε4 allele. CONCLUSIONS: Our findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging

Relationships between lead biomarkers and diurnal salivary cortisol indices in pregnant women from Mexico City: a cross-sectional study

Background: Lead (Pb) exposure during pregnancy may increase the risk of adverse maternal, infant, or childhood health outcomes by interfering with hypothalamic-pituitary-adrenal-axis function. We examined relationships between maternal blood or bone Pb concentrations and features of diurnal cortisol profiles in 936 pregnant women from Mexico City. Methods: From 2007–11 we recruited women from hospitals/clinics affiliated with the Mexican Social Security System. Pb was measured in blood (BPb) during the second trimester and in mothers’ tibia and patella 1-month postpartum. We characterized maternal HPA-axis function using 10 timed salivary cortisol measurements collected over 2-days (mean: 19.7, range: 14–35 weeks gestation). We used linear mixed models to examine the relationship between Pb biomarkers and cortisol area under the curve (AUC), awakening response (CAR), and diurnal slope. Results: After adjustment for confounders, women in the highest quintile of BPb concentrations had a reduced CAR (Ratio: −13%; Confidence Interval [CI]: −24, 1, p-value for trend < 0.05) compared to women in the lowest quintile. Tibia/patella Pb concentrations were not associated with CAR, but diurnal cortisol slopes were suggestively flatter among women in the highest patella Pb quantile compared to women in the lowest quantile (Ratio: 14%; CI: −2, 33). BPb and bone Pb concentrations were not associated with cortisol AUC. Conclusions: Concurrent blood Pb levels were associated with cortisol awakening response in these pregnant women and this might explain adverse health outcomes associated with Pb. Further research is needed to confirm these results and determine if other environmental chemicals disrupt hypothalamic-pituitary-adrenal-axis function during pregnancy

The Association of Long-Term Exposure to Particulate Matter Air Pollution with Brain MRI Findings: The ARIC Study.

BACKGROUND: Increasing evidence links higher particulate matter (PM) air pollution exposure to late-life cognitive impairment. However, few studies have considered associations between direct estimates of long-term past exposures and brain MRI findings indicative of neurodegeneration or cerebrovascular disease. OBJECTIVE: Our objective was to quantify the association between brain MRI findings and PM exposures approximately 5 to 20 y prior to MRI in the Atherosclerosis Risk in Communities (ARIC) study. METHODS: ARIC is based in four U.S. sites: Washington County, Maryland; Minneapolis suburbs, Minnesota; Forsyth County, North Carolina; and Jackson, Mississippi. A subset of ARIC participants underwent 3T brain MRI in 2011-2013 (n=1,753). We estimated mean exposures to PM with an aerodynamic diameter less than 10 or 2.5μm (PM RESULTS: In pooled analyses, higher mean PM CONCLUSIONS: Long-term past PM exposure in was not associated with markers of cerebrovascular disease. Higher long-term past PM exposures were associated with smaller deep-gray volumes overall, and higher P

Mitochondrial haplogroups modify the effect of black carbon on age-related cognitive impairment

Background: Traffic-related air pollution has been linked with impaired cognition in older adults, possibly due to effects of oxidative stress on the brain. Mitochondria are the main source of cellular oxidation. Haplogroups in mitochondrial DNA (mtDNA) mark individual differences in oxidative potential and are possible determinants of neurodegeneration. The aim of this study was to investigate whether mtDNA haplogroups determined differential susceptibility to cognitive effects of long-term exposure to black carbon (BC), a marker of traffic-related air pollution. Methods: We investigated 582 older men (72 ± 7 years) in the VA Normative Aging Study cohort with ≤4 visits per participant (1.8 in average) between 1995–2007. Low (≤25) Mini Mental State Examination (MMSE) was used to assess impaired cognition in multiple domains. We fitted repeated-measure logistic regression using validated-LUR BC estimated in the year before their first visit at the participant’s address. Results: Mitochondrial haplotyping identified nine haplogroups phylogenetically categorized in four clusters. BC showed larger effect on MMSE in Cluster 4 carriers, including I, W and X haplogroups, [OR = 2.7; 95% CI (1.3-5.6)], moderate effect in Cluster 1, including J and T haplogroups [OR = 1.6; 95% CI: (0.9-2.9)], and no effect in Cluster 2 (H and V haplogroups) [OR = 1.1; 95% CI: (0.8-1.5)] or Cluster 3 (K and U haplogroups) [OR = 1.0; 95% CI: (0.6-1.6)]. BC effect varied only moderately across the I, X, and W haplogroups or across the J and T haplogroups. Conclusions: 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. MtDNA haplotypes may modify individual susceptibility to the particle cognitive effects