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ObjectiveTo examine whether late-life exposure to PM2.5 (particulate matter with aerodynamic diameters MethodsAD pattern similarity (AD-PS) scores, developed by supervised machine learning and validated with MRI data from the Alzheimer’s Disease Neuroimaging Initiative, were used to capture high-dimensional gray matter atrophy in brain areas vulnerable to AD (e.g., amygdala, hippocampus, parahippocampal gyrus, thalamus, inferior temporal lobe areas, and midbrain). Using participants' addresses and air monitoring data, we implemented a spatiotemporal model to estimate 3-year average exposure to PM2.5 preceding MRI-1. General linear models were used to examine the association between PM2.5 and AD-PS scores (baseline and 5-year standardized change), accounting for potential confounders and white matter lesion volumes.ResultsFor 1,365 women 77.9 ± 3.7 years of age in 2005 to 2006, there was no association between PM2.5 and baseline AD-PS score in cross-sectional analyses (β = −0.004; 95% confidence interval [CI] −0.019 to 0.011). Longitudinally, each interquartile range increase of PM2.5 (2.82 µg/m3) was associated with increased AD-PS scores during the follow-up, equivalent to a 24% (hazard ratio 1.24, 95% CI 1.14–1.34) increase in AD risk over 5 years (n = 712, age 77.4 ± 3.5 years). This association remained after adjustment for sociodemographics, intracranial volume, lifestyle, clinical characteristics, and white matter lesions and was present with levels below US regulatory standards (3).ConclusionsLate-life exposure to PM2.5 is associated with increased neuroanatomic risk of AD, which may not be explained by available indicators of cerebrovascular damage.

ObjectiveTo examine whether long-chain omega-3 polyunsaturated fatty acid (LCn3PUFA) levels modify the potential neurotoxic effects of particle matter with diameters 2.5) exposure on normal-appearing brain volumes among dementia-free elderly women.MethodsA total of 1,315 women (age 65–80 years) free of dementia were enrolled in an observational study between 1996 and 1999 and underwent structural brain MRI in 2005 to 2006. According to prospectively collected and geocoded participant addresses, we used a spatiotemporal model to estimate the 3-year average PM2.5 exposure before the MRI. We examined the joint associations of baseline LCn3PUFAs in red blood cells (RBCs) and PM2.5 exposure with brain volumes in generalized linear models.ResultsAfter adjustment for potential confounders, participants with higher levels of RBC LCn3PUFA had significantly greater volumes of white matter and hippocampus. For each interquartile increment (2.02%) in omega-3 index, the average volume was 5.03 cm3 (p < 0.01) greater in the white matter and 0.08 cm3 (p = 0.03) greater in the hippocampus. The associations with RBC docosahexaenoic acid and eicosapentaenoic acid levels were similar. Higher LCn3PUFA attenuated the inverse associations between PM2.5 exposure and white matter volumes in the total brain and multimodal association areas (frontal, parietal, and temporal; all p for interaction ConclusionsFindings from this prospective cohort study among elderly women suggest that the benefits of LCn3PUFAs on brain aging may include the protection against potential adverse effects of air pollution on white matter volumes.

Background: Aging is a complex process that results from metabolic activities such as those that generate reactive oxygen species. Metabolomic profiling, an emerging technology, may shed light on metabolites associated with aging and identify key changes associated with premature aging. Methods: A total of 370 metabolites were profiled using liquid chromatography tandem mass spectroscopy (LC-MS) in plasma from 1153 healthy, control subjects in the Women’s Health Initiative. Metabolite levels were log-transformed and standardized, and each considered individually in statistical models. Linear regression models were created with the metabolite as the outcome and age as the primary exposure: Results: The median age of the women was 68 years (interquartile range 62-72). After multivariate adjustment, thirty-nine metabolites were significantly associated with age >75, including 12 acylcarnitines, 11 free fatty acids, 9 fatty acid derivatives, 2 amino acids, and 5 additional metabolites. Of these, octadecenoyl-L-carnitine (C18:1) had the strongest age association, with levels 0.70 SD (95% CI: 0.48-0.92) higher on average among women > 75 years compared to women Conclusions: Multiple metabolites involved in mitochondrial fatty acid oxidation, as well as several associated with insulin resistance, have a strong relationship with age, even after adjusting for multiple age-associated factors.

Objective: We investigated whether PM 2.5 -mediated autonomic modulation depends on individual coronary risk profiles. Methods: Five-minute average heart rate (HR) and heart rate variability (HRV, including standard deviation of normal-to-normal intervals [SDNN], square root of the mean squared differences of successive NN intervals [rMSSD] high frequency [HF]) were measured from 24-hour ambulatory electrocardiograms, and personal PM 2.5 5 exposures were monitored in a prospective study of 10 male boilermakers (aged 34.3 ± 8.1 years). We used the Framingham score to classify individuals into low (score = 1-3) and high (score = 5-6) risk categories. Mixed-effect models were used for statistical analyses. Results: Each 1-mg/m 3 increase in the preceding 4-hour moving average PM 2.5 was associated with HR increase (5.3 beats/min) and HRV reduction (11.7%, confidence interval [CI] = 6.2-17.1% for 5DNN; 11.1%, Cl = 3.1-19.1% for rMSSD; 16.6%, CI = 1.5-31.7% for HF). Greater responses (2- to 4-fold differences) were observed in high-risk subjects than in low-risk subjects. Conclusions: Our study suggests that adverse autonomic responses to metal particulate are aggravated in workers with higher coronary risk profiles.

Background It is often difficult and expensive to make direct measurements of an individual's occupational or environmental exposures in large epidemiologic studies. Methods In this study, we used information collected in validation studies to develop a prediction rule for assessing exposure in a study with no direct measurement. We established a prediction rule through mixed-effect modeling of direct measurement data and information on observable exposure predictors and their interactions. Specifically, we used 383 measures of whole-body vibration from 247 professional taxi drivers and attempted to quantify vibration exposures for individuals in a large study on low back pain. Results Using the "jackknife method," we found that our prediction rule had an acceptably low relative prediction error of 11% (95% confidence interval-10-12%). Implementing the prediction rule would result in measurement errors independent of low back pain and of all identified and observable predictors of whole-body vibration. We applied the predicted levels to compute each person's daily exposure, and found a strong association between the predicted daily whole-body vibration exposure and prevalence of low back pain. This supported the construct validity of the exposure prediction rule. Conclusions The predictive and construct validity of our prediction rule suggests that this general statistical approach can be useful in other occupational settings to improve the quality of exposure assessment.

The impact of air pollution on survival after stroke is unknown. We examined the impact of outdoor air pollution on stroke survival by studying a population-based cohort.All patients who experienced their first-ever stroke between 1995 and 2005 in a geographically defined part of London, where road traffic contributes to spatial variation in air pollution, were followed up to mid-2006. Outdoor concentrations of nitrogen dioxide and particulate matter10 microm in diameter modeled at a 20-m grid point resolution for 2002 were linked to residential postal codes. Hazard ratios were adjusted for age, sex, social class, ethnicity, smoking, alcohol consumption, prestroke functional ability, pre-existing medical conditions, stroke subtype and severity, hospital admission, and neighborhood socioeconomic deprivation.There were 1856 deaths among 3320 patients. Median survival was 3.7 years (interquartile range, 0.1 to 10.8). Mean exposure levels were 41 microg/m(3) (SD, 3.3; range, 32.2 to 103.2) for nitrogen dioxide and 25 microg/m(3) (SD, 1.3; range, 22.7 to 52) for particulate matter10 microm in diameter. A 10-microg/m(3) increase in nitrogen dioxide was associated with a 28% (95% CI, 11% to 48%) increase in risk of death. A 10-microg/m(3) increase in particulate matter10 mum in diameter was associated with a 52% (6% to 118%) increase in risk of death. Reduced survival was apparent throughout the follow-up period, ruling out short-term mortality displacement.Survival after stroke was lower among patients living in areas with higher levels of outdoor air pollution. If causal, a 10-microg/m(3) reduction in nitrogen dioxide exposure might be associated with a reduction in mortality comparable to that for stroke units. Improvements in outdoor air quality might contribute to better survival after stroke.