Association of improved air quality with lower dementia risk in older women.

Late-life ambient air pollution is a risk factor for brain aging, but it remains unknown if improved air quality (AQ) lowers dementia risk. We studied a geographically diverse cohort of older women dementia free at baseline in 2008 to 2012 (n = 2,239, aged 74 to 92). Incident dementia was centrally adjudicated annually. Yearly mean concentrations of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) were estimated using regionalized national universal kriging models and averaged over the 3-y period before baseline (recent exposure) and 10 y earlier (remote exposure). Reduction from remote to recent exposures was used as the indicator of improved AQ. Cox proportional hazard ratios (HRs) for dementia risk associated with AQ measures were estimated, adjusting for sociodemographic, lifestyle, and clinical characteristics. We identified 398 dementia cases during follow up (median = 6.1 y). PM2.5 and NO2 reduced significantly over the 10 y before baseline. Larger AQ improvement was associated with reduced dementia risks (HRPM2.5 0.80 per 1.78 µg/m3, 95% CI 0.71-0.91; HRNO2 0.80 per 3.91 parts per billion, 95% CI 0.71-0.90), equivalent to the lower risk observed in women 2.4 y younger at baseline. Higher PM2.5 at baseline was associated with higher dementia risk (HRPM2.5 1.16 per 2.90 µg/m3, 95% CI 0.98-1.38), but the lower dementia risk associated with improved AQ remained after further adjusting for recent exposure. The observed associations did not substantially differ by age, education, geographic region, Apolipoprotein E e4 genotypes, or cardiovascular risk factors. Long-term AQ improvement in late life was associated with lower dementia risk in older women.

Association between particulate air pollution and hypertensive disorders in pregnancy: A retrospective cohort study.

BACKGROUND: Epidemiological findings regarding the association of particulate matter ≤2.5 µm (PM2.5) exposure with hypertensive disorders in pregnancy (HDP) are inconsistent; evidence for HDP risk related to PM2.5 components, mixture effects, and windows of susceptibility is limited. We aimed to investigate the relationships between HDP and exposure to PM2.5 during pregnancy. METHODS AND FINDINGS: A large retrospective cohort study was conducted among mothers with singleton pregnancies in Kaiser Permanente Southern California from 2008 to 2017. HDP were defined by International Classification of Diseases-9/10 (ICD-9/10) diagnostic codes and were classified into 2 subcategories based on the severity of HDP: gestational hypertension (GH) and preeclampsia and eclampsia (PE-E). Monthly averages of PM2.5 total mass and its constituents (i.e., sulfate, nitrate, ammonium, organic matter, and black carbon) were estimated using outputs from a fine-resolution geoscience-derived model. Multilevel Cox proportional hazard models were used to fit single-pollutant models; quantile g-computation approach was applied to estimate the joint effect of PM2.5 constituents. The distributed lag model was applied to estimate the association between monthly PM2.5 exposure and HDP risk. This study included 386,361 participants (30.3 ± 6.1 years) with 4.8% (17,977/373,905) GH and 5.0% (19,381/386,361) PE-E cases, respectively. In single-pollutant models, we observed increased relative risks for PE-E associated with exposures to PM2.5 total mass [adjusted hazard ratio (HR) per interquartile range: 1.07, 95% confidence interval (CI) [1.04, 1.10] p < 0.001], black carbon [HR = 1.12 (95% CI [1.08, 1.16] p < 0.001)] and organic matter [HR = 1.06 (95% CI [1.03, 1.09] p < 0.001)], but not for GH. The population attributable fraction for PE-E corresponding to the standards of the US Environmental Protection Agency (9 µg/m3) was 6.37%. In multi-pollutant models, the PM2.5 mixture was associated with an increased relative risk of PE-E ([HR = 1.05 (95% CI [1.03, 1.07] p < 0.001)], simultaneous increase in PM2.5 constituents of interest by a quartile) and PM2.5 black carbon gave the greatest contribution of the overall mixture effects (71%) among all individual constituents. The susceptible window is the late first trimester and second trimester. Furthermore, the risks of PE-E associated with PM2.5 exposure were significantly higher among Hispanic and African American mothers and mothers who live in low- to middle-income neighborhoods (p < 0.05 for Cochran's Q test). Study limitations include potential exposure misclassification solely based on residential outdoor air pollution, misclassification of disease status defined by ICD codes, the date of diagnosis not reflecting the actual time of onset, and lack of information on potential covariates and unmeasured factors for HDP. CONCLUSIONS: Our findings add to the literature on associations between air pollution exposure and HDP. To our knowledge, this is the first study reporting that specific air pollution components, mixture effects, and susceptible windows of PM2.5 may affect GH and PE-E differently.

Air pollution and age-dependent changes in emotional behavior across early adolescence in the U.S.

Recent studies have linked air pollution to increased risk for behavioral problems during development, albeit with inconsistent findings. Additional longitudinal studies are needed that consider how emotional behaviors may be affected when exposure coincides with the transition to adolescence - a vulnerable time for developing mental health difficulties. This study investigates if annual average PM2.5 and NO2 exposure at ages 9-10 years moderates age-related changes in internalizing and externalizing behaviors over a 2-year follow-up period in a large, nationwide U.S. sample of participants from the Adolescent Brain Cognitive Development (ABCD) Study®. Air pollution exposure was estimated based on the residential address of each participant using an ensemble-based modeling approach. Caregivers answered questions from the Child Behavior Checklist (CBCL) at the baseline, 1-year follow-up, and 2-year follow-up visits, for a total of 3 waves of data; from the CBCL we obtained scores on internalizing and externalizing problems plus 5 syndrome scales (anxious/depressed, withdrawn/depressed, rule-breaking behavior, aggressive behavior, and attention problems). Zero-inflated negative binomial models were used to examine both the main effect of age as well as the interaction of age with each pollutant on behavior while adjusting for various socioeconomic and demographic characteristics. Against our hypothesis, there was no evidence that greater air pollution exposure was related to more behavioral problems with age over time.

20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

Associations of Autism Spectrum Disorder with PM2.5 Components: A Comparative Study Using Two Different Exposure Models.

This retrospective cohort study examined associations of autism spectrum disorder (ASD) with prenatal exposure to major fine particulate matter (PM2.5) components estimated using two independent exposure models. The cohort included 318 750 mother-child pairs with singleton deliveries in Kaiser Permanente Southern California hospitals from 2001 to 2014 and followed until age five. ASD cases during follow-up (N = 4559) were identified by ICD codes. Prenatal exposures to PM2.5, elemental (EC) and black carbon (BC), organic matter (OM), nitrate (NO3-), and sulfate (SO42-) were constructed using (i) a source-oriented chemical transport model and (ii) a hybrid model. Exposures were assigned to each maternal address during the entire pregnancy, first, second, and third trimester. In single-pollutant models, ASD was associated with pregnancy-average PM2.5, EC/BC, OM, and SO42- exposures from both exposure models, after adjustment for covariates. The direction of effect estimates was consistent for EC/BC and OM and least consistent for NO3-. EC/BC, OM, and SO42- were generally robust to adjustment for other components and for PM2.5. EC/BC and OM effect estimates were generally larger and more consistent in the first and second trimester and SO42- in the third trimester. Future PM2.5 composition health effect studies might consider using multiple exposure models and a weight of evidence approach when interpreting effect estimates.

Modeling spatially varying compliance effects of PM2.5 exposure reductions on gestational diabetes mellitus in southern California: Results from electronic health record data of a large pregnancy cohort.

Gestational diabetes mellitus (GDM) is a major pregnancy complication affecting approximately 14.0% of pregnancies around the world. Air pollution exposure, particularly exposure to PM2.5, has become a major environmental issue affecting health, especially for vulnerable pregnant women. Associations between PM2.5 exposure and adverse birth outcomes are generally assumed to be the same throughout a large geographical area. However, the effects of air pollution on health can very spatially in subpopulations. Such spatially varying effects are likely due to a wide range of contextual neighborhood and individual factors that are spatially correlated, including SES, demographics, exposure to housing characteristics and due to different composition of particulate matter from different emission sources. This combination of elevated environmental hazards in conjunction with socioeconomic-based disparities forms what has been described as a "double jeopardy" for marginalized sub-populations. In this manuscript our analysis combines both an examination of spatially varying effects of a) unit-changes in exposure and examines effects of b) changes from current exposure levels down to a fixed compliance level, where compliance levels correspond to the Air Quality Standards (AQS) set by the U.S. Environmental Protection Agency (EPA) and World Health Organization (WHO) air quality guideline values. Results suggest that exposure reduction policies should target certain "hotspot" areas where size and effects of potential reductions will reap the greatest rewards in terms of health benefits, such as areas of southeast Los Angeles County which experiences high levels of PM2.5 exposures and consist of individuals who may be particularly vulnerable to the effects of air pollution on the risk of GDM.

The relationship between optimism, MCI, and dementia among postmenopausal women.

OBJECTIVES: The relationship between optimism and cognitive functioning is not fully understood. We examined the association of optimism with risk of mild cognitive impairment (MCI) and dementia in the Women's Health Initiative Memory Study (WHIMS). METHODS: Optimism was measured by the Life Orientation Test-Revised (LOT-R) total score, and optimism and pessimism subscales. A panel of experts adjudicated cognitive endpoints based on annual cognitive assessments. We used cox proportional hazard regression models to examine the association of LOT-R total score and optimism and pessimism sub-scores with MCI/dementia. We also examined the relationship between vascular disease, LOT-R total score, optimism and pessimism, and cognition. RESULTS: Mean age was 70.5 (SD = 3.9) years. The sample (N = 7249) was 87% white, and 29.8% of participants had < 12 years of education. Total LOT-R score (HR = 0.96, 95% CI: 0.94, 0.98, p < 0.001) was associated with lower risk of combined MCI or dementia. More pessimism (HR = 1.08, 95% CI: 1.05, 1.11, p < 0.0001) was associated with higher risk of MCI or dementia after adjustment for ethnicity, education, vascular disease, and depression. No significant relationships emerged from the optimism subscale. CONCLUSION: These data suggest that less pessimism, but not more optimism, was associated with a lower risk of MCI and dementia.

Associations of dietary cholesterol and fat, blood lipids, and risk for dementia in older women vary by APOE genotype.

INTRODUCTION: Whether apolipoprotein E's (APOE's) involvement in lipid metabolism contributes to Alzheimer's disease (AD) risk remains unknown. METHODS: Incident probable dementia and cognitive impairment (probable dementia+mild cognitive impairment) were analyzed in relation to baseline serum lipids (total, low-density lipoprotein [LDL], high-density lipoprotein [HDL], non-HDL cholesterol, total-to-HDL, LDL-to-HDL, remnant cholesterol, and triglycerides) using Mendelian randomization in 5358 postmenopausal women from the Women's Health Initiative Memory Study. We also examined associations of baseline dietary cholesterol and fat with lipids based on APOE status. RESULTS: After an average of 11.13 years, less favorable lipid levels related to greater dementia and cognitive impairment risk. Dementia (odds ratio [OR] = 3.13; 95% confidence interval [CI]: 2.31 to 4.24) and cognitive impairment (OR = 2.38; 95% CI: 1.85 to 3.06) risk were greatest in relation to higher remnant cholesterol levels. Greater cholesterol consumption related to poorer lipids in APOE4+ compared to APOE3 carriers. DISCUSSION: APOE4+ carriers consuming more cholesterol had less favorable lipids, which were associated with greater dementia and cognitive impairment risk. HIGHLIGHTS: Less favorable serum lipids were associated with higher dementia incidence. Mendelian randomization findings suggest causality between lipids and dementia. Lipid levels in older women may be clinical indicators of dementia risk. APOE4 carriers had poorest lipid profiles in relation to cholesterol consumption. APOE risk for dementia may be modifiable through lipid management.

Air quality improvement and cognitive decline in community-dwelling older women in the United States: A longitudinal cohort study.

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. Air quality (AQ) improvement has been associated with improved cardiopulmonary health and decreased mortality, but to the best of our knowledge, no studies have examined the association with cognitive function. We examined whether AQ improvement was associated with slower rate of cognitive decline in older women aged 74 to 92 years. METHODS AND FINDINGS: We studied a cohort of 2,232 women residing in the 48 contiguous US states that were recruited from more than 40 study sites located in 24 states and Washington, DC from the Women's Health Initiative (WHI) Memory Study (WHIMS)-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) study. They were predominantly non-Hispanic White women and were dementia free at baseline in 2008 to 2012. Measures of annual (2008 to 2018) cognitive function included the modified Telephone Interview for Cognitive Status (TICSm) and the telephone-based California Verbal Learning Test (CVLT). We used regionalized universal kriging models to estimate annual concentrations (1996 to 2012) of fine particulate matter (PM2.5) and nitrogen dioxide (NO2) at residential locations. Estimates were aggregated to the 3-year average immediately preceding (recent exposure) and 10 years prior to (remote exposure) WHIMS-ECHO enrollment. Individual-level improved AQ was calculated as the reduction from remote to recent exposures. Linear mixed effect models were used to examine the associations between improved AQ and the rates of cognitive declines in TICSm and CVLT trajectories, adjusting for sociodemographic (age; geographic region; race/ethnicity; education; income; and employment), lifestyle (physical activity; smoking; and alcohol), and clinical characteristics (prior hormone use; hormone therapy assignment; depression; cardiovascular disease (CVD); hypercholesterolemia; hypertension; diabetes; and body mass index [BMI]). For both PM2.5 and NO2, AQ improved significantly over the 10 years before WHIMS-ECHO enrollment. During a median of 6.2 (interquartile range [IQR] = 5.0) years of follow-up, declines in both general cognitive status (ß = -0.42/year, 95% CI: -0.44, -0.40) and episodic memory (ß = -0.59/year, 95% CI: -0.64, -0.54) were observed. Greater AQ improvement was associated with slower decline in TICSm (ßPM2.5improvement = 0.026 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.001, 0.05; ßNO2improvement = 0.034 per year for improved NO2 by each IQR = 3.92 parts per billion [ppb] reduction, 95% CI: 0.01, 0.06) and CVLT (ßPM2.5 improvement = 0.070 per year for improved PM2.5 by each IQR = 1.79 µg/m3 reduction, 95% CI: 0.02, 0.12; ßNO2improvement = 0.060 per year for improved NO2 by each IQR = 3.97 ppb reduction, 95% CI: 0.005, 0.12) after adjusting for covariates. The respective associations with TICSm and CVLT were equivalent to the slower decline rate found with 0.9 to 1.2 and1.4 to 1.6 years of younger age and did not significantly differ by age, region, education, Apolipoprotein E (ApoE) e4 genotypes, or cardiovascular risk factors. The main limitations of this study include measurement error in exposure estimates, potential unmeasured confounding, and limited generalizability. CONCLUSIONS: In this study, we found that greater improvement in long-term AQ in late life was associated with slower cognitive declines in older women. This novel observation strengthens the epidemiologic evidence of an association between air pollution and cognitive aging.

Evidence of susceptibility to autism risks associated with early life ambient air pollution: A systematic review.

BACKGROUND: Many studies have found associations between early life air pollution exposure and subsequent onset of autism spectrum disorder (ASD). However, characteristics that affect susceptibility remain unclear. OBJECTIVE: This systematic review examined epidemiologic studies on the modifying roles of social, child, genetic and maternal characteristics in associations between prenatal and early postnatal air pollution exposure and ASD. METHODS: A systematic literature search in PubMed and Embase was conducted. Studies that examined modifiers of the association between air pollution and ASD were included. RESULTS: A total of 19 publications examined modifiers of the associations between early life air pollution exposures and ASD. In general, estimates of effects on risk of ASD in boys were larger than in girls (based on 11 studies). Results from studies of effects of family education (2 studies) and neighborhood deprivation (2 studies) on air pollution-ASD associations were inconsistent. Limited data (1 study) suggest pregnant women with insufficient folic acid intake might be more susceptible to ambient particulate matter less than 2.5 µm (PM2.5) and 10 µm (PM10) in aerodynamic diameter, and to nitrogen dioxide (NO2). Children of mothers with gestational diabetes had increased risk of ozone-associated ASD (1 study). Two genetic studies reported that copy number variations may amplify the effect of ozone, and MET rs1858830 CC genotype may augment effects of PM and near-roadway pollutants on ASD. CONCLUSIONS: Child's sex, maternal nutrition or diabetes, socioeconomic factors, and child risk genotypes were reported to modify the effect of early-life air pollutants on ASD risk in the epidemiologic literature. However, the sparsity of studies on comparable modifying hypotheses precludes conclusive findings. Further research is needed to identify susceptible populations and potential targets for preventive intervention.

B vitamin intakes modify the association between particulate air pollutants and incidence of all-cause dementia: Findings from the Women's Health Initiative Memory Study.

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.

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer's disease.

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 µg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

Particulate Air Pollutants and Trajectories of Depressive Symptoms in Older Women.

OBJECTIVES: Although several environmental factors contribute to the etiology of late-life depressive symptoms, the role of ambient air pollution has been understudied. Experimental data support the neurotoxicity of airborne particulate matter with aerodynamic diameter of ≤2.5 µm (PM2.5), but it remains unclear whether long-term exposure is associated with late-life depressive symptoms. Our secondary aim was to explore whether the observed associations between exposure and depressive symptoms are explained by dementia risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective community-dwelling cohort study from the Women's Health Initiative Study of Cognitive Aging (1999-2010). Our analyses included 1,989 older women (baseline age 73.3 ± 3.75) with no prior depression or cognitive impairment. MEASUREMENTS: Participants completed annual assessments of depressive symptoms (15-item Geriatric Depression Scale). Average ambient PM2.5 exposure at the residential location was estimated by spatiotemporal modeling for the 3-years preceding each neuropsychological assessment. Participants underwent separate annual examinations for incident dementia defined by DSM-IV. Latent-class mixture models examined the association between PM2.5 and identified trajectories of symptoms. RESULTS: Six trajectories of depressive symptoms were identified. Across all women, PM2.5 exposure was positively associated with depressive symptoms. The effect was especially strong in two clusters with sustained depressive symptoms (n = 625 sustained-mild [31%]; n = 125 sustained-moderate; [6%]). Among those with sustained-moderate symptoms, the estimated adverse effect of PM2.5 exposure was greater than that of hypertension. Among women without dementia, associations were modestly attenuated. CONCLUSION: Long-term exposure to ambient fine particles was associated with increased depressive symptoms among older women without prior depression or cognitive impairment.

Using high-dimensional machine learning methods to estimate an anatomical risk factor for Alzheimer's disease across imaging databases.

INTRODUCTION: The main goal of this work is to investigate the feasibility of estimating an anatomical index that can be used as an Alzheimer's disease (AD) risk factor in the Women's Health Initiative Magnetic Resonance Imaging Study (WHIMS-MRI) using MRI data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized imaging database of AD patients and cognitively normal subjects. We called this index AD Pattern Similarity (AD-PS) scores. To demonstrate the construct validity of the scores, we investigated their associations with several AD risk factors. The ADNI and WHIMS imaging databases were collected with different goals, populations and data acquisition protocols: it is important to demonstrate that the approach to estimating AD-PS scores can bridge these differences. METHODS: MRI data from both studies were processed using high-dimensional warping methods. High-dimensional classifiers were then estimated using the ADNI MRI data. Next, the classifiers were applied to baseline and follow-up WHIMS-MRI GM data to generate the GM AD-PS scores. To study the validity of the scores we investigated associations between GM AD-PS scores at baseline (Scan 1) and their longitudinal changes (Scan 2 -Scan 1) with: 1) age, cognitive scores, white matter small vessel ischemic disease (WM SVID) volume at baseline and 2) age, cognitive scores, WM SVID volume longitudinal changes respectively. In addition, we investigated their associations with time until classification of independently adjudicated status in WHIMS-MRI. RESULTS: Higher GM AD-PS scores from WHIMS-MRI baseline data were associated with older age, lower cognitive scores, and higher WM SVID volume. Longitudinal changes in GM AD-PS scores (Scan 2 - Scan 1) were also associated with age and changes in WM SVID volumes and cognitive test scores. Increases in the GM AD-PS scores predicted decreases in cognitive scores and increases in WM SVID volume. GM AD-PS scores and their longitudinal changes also were associated with time until classification of cognitive impairment. Finally, receiver operating characteristic curves showed that baseline GM AD-PS scores of cognitively normal participants carried information about future cognitive status determined during follow-up. DISCUSSION: We applied a high-dimensional machine learning approach to estimate a novel AD risk factor for WHIMS-MRI study participants using ADNI data. The GM AD-PS scores showed strong associations with incident cognitive impairment and cross-sectional and longitudinal associations with age, cognitive function, cognitive status and WM SVID volume lending support to the ongoing validation of the GM AD-PS score.

Long-Term Ambient Temperature and Externalizing Behaviors in Adolescents.

The climate-violence relationship has been debated for decades, and yet most of the supportive evidence has come from ecological or cross-sectional analyses with very limited long-term exposure data. We conducted an individual-level, longitudinal study to investigate the association between ambient temperature and externalizing behaviors of urban-dwelling adolescents. Participants (n = 1,287) in the Risk Factors for Antisocial Behavior Study, in California, were examined during 2000-2012 (aged 9-18 years) with repeated assessments of their externalizing behaviors (e.g., aggression, delinquency). Ambient temperature data were obtained from the local meteorological information system. In adjusted multilevel models, aggressive behaviors significantly increased with rising average temperatures (per 1°C increment) in the preceding 1, 2, or 3 years (respectively, ß = 0.23, 95% confidence interval (CI): 0.00, 0.46; ß = 0.35, 95% CI: 0.06, 0.63; or ß = 0.41, 95% CI: 0.08, 0.74), equivalent to 1.5-3.0 years of delay in age-related behavioral maturation. These associations were slightly stronger among girls and families of lower socioeconomic status but greatly diminished in neighborhoods with more green space. No significant associations were found with delinquency. Our study provides the first individual-level epidemiologic evidence supporting the adverse association of long-term ambient temperature and aggression. Similar approaches to studying meteorology and violent crime might further inform scientific debates on climate change and collective violence.

Source Characterization and Exposure Modeling of Gas-Phase Polycyclic Aromatic Hydrocarbon (PAH) Concentrations in Southern California.

Airborne exposures to polycyclic aromatic hydrocarbons (PAHs) are associated with adverse health outcomes. Because personal air measurements of PAHs are labor intensive and costly, spatial PAH exposure models are useful for epidemiological studies. However, few studies provide adequate spatial coverage to reflect intra-urban variability of ambient PAHs. In this study, we collected 39-40 weekly gas-phase PAH samples in southern California twice in summer and twice in winter, 2009, in order to characterize PAH source contributions and develop spatial models that can estimate gas-phase PAH concentrations at a high resolution. A spatial mixed regression model was constructed, including such variables as roadway, traffic, land-use, vegetation index, commercial cooking facilities, meteorology, and population density. Cross validation of the model resulted in an R2 of 0.66 for summer and 0.77 for winter. Results showed higher total PAH concentrations in winter. Pyrogenic sources, such as fossil fuels and diesel exhaust, were the most dominant contributors to total PAHs. PAH sources varied by season, with a higher fossil fuel and wood burning contribution in winter. Spatial autocorrelation accounted for a substantial amount of the variance in total PAH concentrations for both winter (56%) and summer (19%). In summer, other key variables explaining the variance included meteorological factors (9%), population density (15%), and roadway length (21%). In winter, the variance was also explained by traffic density (16%). In this study, source characterization confirmed the dominance of traffic and other fossil fuel sources to total measured gas-phase PAH concentrations while a spatial exposure model identified key predictors of PAH concentrations. Gas-phase PAH source characterization and exposure estimation is of high utility to epidemiologist and policy makers interested in understanding the health impacts of gas-phase PAHs and strategies to reduce emissions.

Constrained Mixed-Effect Models with Ensemble Learning for Prediction of Nitrogen Oxides Concentrations at High Spatiotemporal Resolution.

Spatiotemporal models to estimate ambient exposures at high spatiotemporal resolutions are crucial in large-scale air pollution epidemiological studies that follow participants over extended periods. Previous models typically rely on central-site monitoring data and/or covered short periods, limiting their applications to long-term cohort studies. Here we developed a spatiotemporal model that can reliably predict nitrogen oxide concentrations with a high spatiotemporal resolution over a long time span (>20 years). Leveraging the spatially extensive highly clustered exposure data from short-term measurement campaigns across 1-2 years and long-term central site monitoring in 1992-2013, we developed an integrated mixed-effect model with uncertainty estimates. Our statistical model incorporated nonlinear and spatial effects to reduce bias. Identified important predictors included temporal basis predictors, traffic indicators, population density, and subcounty-level mean pollutant concentrations. Substantial spatial autocorrelation (11-13%) was observed between neighboring communities. Ensemble learning and constrained optimization were used to enhance reliability of estimation over a large metropolitan area and a long period. The ensemble predictions of biweekly concentrations resulted in an R2 of 0.85 (RMSE: 4.7 ppb) for NO2 and 0.86 (RMSE: 13.4 ppb) for NOx. Ensemble learning and constrained optimization generated stable time series, which notably improved the results compared with those from initial mixed-effects models.

Ambient air pollution and neurotoxicity on brain structure: Evidence from women's health initiative memory study.

OBJECTIVE: The aim of this study was to examine the putative adverse effects of ambient fine particulate matter (PM2.5 : PM with aerodynamic diameters <2.5µm) on brain volumes in older women. METHODS: We conducted a prospective study of 1,403 community-dwelling older women without dementia enrolled in the Women's Health Initiative Memory Study, 1996-1998. Structural brain magnetic resonance imaging scans were performed at the age of 71-89 years in 2005-2006 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM2.5 exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM2.5 and brain volumes, adjusting for intracranial volumes and potential confounders. RESULTS: Older women with greater PM2.5 exposures had significantly smaller WM, but not GM, volumes, independent of geographical region, demographics, socioeconomic status, lifestyles, and clinical characteristics, including cardiovascular risk factors. For each interquartile increment (3.49µg/m(3) ) of cumulative PM2.5 exposure, the average WM volume (WMV; 95% confidence interval) was 6.23cm(3) (3.72-8.74) smaller in the total brain and 4.47cm(3) (2.27-6.67) lower in the association areas, equivalent to 1 to 2 years of brain aging. The adverse PM2.5 effects on smaller WMVs were present in frontal and temporal lobes and corpus callosum (all p values <0.01). Hippocampal volumes did not differ by PM2.5 exposure. INTERPRETATION: PM2.5 exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies.

Sleep duration, cognitive decline, and dementia risk in older women.

INTRODUCTION: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. METHODS: We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. RESULTS: We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. DISCUSSION: In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors.

Air pollution from biomass burning disrupts early adolescent cortical microarchitecture development.

Exposure to outdoor particulate matter (PM2.5) represents a ubiquitous threat to human health, and particularly the neurotoxic effects of PM2.5 from multiple sources may disrupt neurodevelopment. Studies addressing neurodevelopmental implications of PM exposure have been limited by small, geographically limited samples and largely focus either on macroscale cortical morphology or postmortem histological staining and total PM mass. Here, we leverage residentially assigned exposure to six, data-driven sources of PM2.5 and neuroimaging data from the longitudinal Adolescent Brain Cognitive Development Study (ABCD Study®), collected from 21 different recruitment sites across the United States. To contribute an interpretable and actionable assessment of the role of air pollution in the developing brain, we identified alterations in cortical microstructure development associated with exposure to specific sources of PM2.5 using multivariate, partial least squares analyses. Specifically, average annual exposure (i.e., at ages 8-10 years) to PM2.5 from biomass burning was related to differences in neurite development across the cortex between 9 and 13 years of age.