Veterans Affairs Normative Aging Study Research Articles

The Costs of Coping: Long-Term Mortality Risk in Aging Men.

Prospective associations between coping and all-cause mortality risk are understudied, particularly among nonmedical samples. We assessed independent and joint associations of multiple components of the transactional stress and coping model with all-cause mortality in a cohort of community-dwelling men. We were particularly interested in how coping effort related to mortality. Participants included 743 men from the Veterans Affairs Normative Aging Study who completed 1+ stress and coping assessment in 1993-2002 (baseline age: M = 68.4, standard deviation [SD] = 7.1) and had mortality follow-up through 2020. The Brief California Coping Inventory assessed coping with a past-month stressor. Cox regression evaluated associations of problem stressfulness, coping strategies, total coping effort, and coping efficiency with all-cause mortality risk. Over a mean follow-up of 16.7 years (SD = 7.1), 473 (64%) men died. Problem stressfulness was not associated with mortality risk (hazard ratio [HR]: 1.07, 95% confidence interval [CI]: 0.98-1.17), adjusted for demographics and health conditions. When examining coping via specific strategies, only social coping was associated with higher mortality risk (HR: 1.15, 95% CI: 1.05-1.26) after Bonferroni correction. Total coping effort was associated with 14% greater risk of all-cause mortality (95% CI: 1.04-1.26), independent of problem stressfulness, demographics, and health conditions. Coping efficiency, a benefit-cost ratio of coping efficacy to total coping effort, was not associated with mortality risk in adjusted models. Total coping effort may be an important indicator for longevity among aging men, above and beyond problem stressfulness and specific coping strategies, which have been the foci in prior research.

Cohort Network: A Knowledge Graph toward Data Dissemination and Knowledge-Driven Discovery for Cohort Studies.

Contemporary environmental health sciences draw on large-scale longitudinal studies to understand the impact of environmental exposures and behavior factors on the risk of disease and identify potential underlying mechanisms. In such studies, cohorts of individuals are assembled and followed up over time. Each cohort generates hundreds of publications, which are typically neither coherently organized nor summarized, hence limiting knowledge-driven dissemination. Hence, we propose a Cohort Network, a multilayer knowledge graph approach to extract exposures, outcomes, and their connections. We applied the Cohort Network on 121 peer-reviewed papers published over the past 10 years from the Veterans Affairs (VA) Normative Aging Study (NAS). The Cohort Network visualized connections between exposures and outcomes across different publications and identified key exposures and outcomes, such as air pollution, DNA methylation, and lung function. We demonstrated the utility of the Cohort Network for new hypothesis generation, e.g., identification of potential mediators of exposure-outcome associations. The Cohort Network can be used by investigators to summarize the cohort's research and facilitate knowledge-driven discovery and dissemination.

Optimism, Daily Stressors, and Emotional Well-Being Over Two Decades in a Cohort of Aging Men.

Growing evidence supports optimism as a health asset, yet how optimism influences well-being and health remains uncertain. We evaluated 1 potential pathway-the association of optimism with daily stress processes-and tested 2 hypotheses. The stressor exposure hypothesis posits that optimism would preserve emotional well-being by limiting exposure to daily stressors. The buffering hypothesis posits that higher optimism would be associated with lower emotional reactivity to daily stressors and more effective emotional recovery from them. Participants were 233 men from the Veterans Affairs Normative Aging Study who completed the Minnesota Multiphasic Personality Inventory-2 Revised Optimism-Pessimism scale in 1986/1991 and participated in up to three 8-day daily diary bursts in 2002-2010 (age at first burst: M = 76.7, SD = 6.5). Daily stressor occurrence, positive affect (PA), and negative affect (NA) were assessed nightly. We evaluated the hypotheses using multilevel structural equation models. Optimism was unrelated to emotional reactivity to or recovery from daily stressors. Higher optimism was associated with higher average daily PA (B = 2.31, 95% Bayesian credible interval [BCI]: 1.24, 3.38) but not NA, independent of stressor exposure. Lower stressor exposure mediated the association of higher optimism with lower daily NA (indirect effect: B = -0.27, 95% BCI: -0.50, -0.09), supporting the stressor exposure hypothesis. Findings from a sample of older men suggest that optimism may be associated with more favorable emotional well-being in later life through differences in stressor exposure rather than emotional stress response. Optimism may preserve emotional well-being among older adults by engaging emotion regulation strategies that occur relatively early in the emotion-generative process.

Short-term exposure to PM2.5 components and renal health: Findings from the Veterans Affairs Normative Aging Study

There is little evidence on the short-term impact of fine particulate matter (PM2.5) on renal health, and the potential interactions and various influences of PM2.5 components on renal health have not been examined. We investigated whether short-term (≤28 days) ambient PM2.5 and 15 PM2.5 components were associated with serum uric acid (SUA), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and odds of incident chronic kidney disease (CKD) using both mixed-effect and Bayesian kernel machine regression (BKMR) models in the Normative Aging Study. This analysis included 2466 study visits from 808 older males enrolled during 1998–2016 with available data. BKMR showed positive relationships of PM2.5 mixture with SUA and odds of CKD, and an inverse relationship with eGFR. In the 28-day exposure window, an interquartile range (IQR) increase in vanadium was associated with a 0.244-mg/dL higher SUA. IQR increases in sulfur and lead were associated with a 1.281- and 1.008-mL/min/1.73 m2 decrease in eGFR, respectively. The same change in sulfur was also associated with a 39% higher odds of CKD. Our findings provide solid evidence supporting short-term adverse effects of PM2.5 on renal health and further highlight that components from oil combustion and regional pollution may be major contributors.

Large-Scale Hypothesis Testing for Causal Mediation Effects with Applications in Genome-wide Epigenetic Studies

In genome-wide epigenetic studies, it is of great scientific interest to assess whether the effect of an exposure on a clinical outcome is mediated through DNA methylations. However, statistical inference for causal mediation effects is challenged by the fact that one needs to test a large number of composite null hypotheses across the whole epigenome. Two popular tests, the Wald-type Sobel’s test and the joint significant test using the traditional null distribution are underpowered and thus can miss important scientific discoveries. In this article, we show that the null distribution of Sobel’s test is not the standard normal distribution and the null distribution of the joint significant test is not uniform under the composite null of no mediation effect, especially in finite samples and under the singular point null case that the exposure has no effect on the mediator and the mediator has no effect on the outcome. Our results explain why these two tests are underpowered, and more importantly motivate us to develop a more powerful divide-aggregate composite-null test (DACT) for the composite null hypothesis of no mediation effect by leveraging epigenome-wide data. We adopted Efron’s empirical null framework for assessing statistical significance of the DACT test. We showed analytically that the proposed DACT method had improved power, and could well control Type I error rate. Our extensive simulation studies showed that, in finite samples, the DACT method properly controlled the Type I error rate and outperformed Sobel’s test and the joint significance test for detecting mediation effects. We applied the DACT method to the U.S. Department of Veterans Affairs Normative Aging Study, an ongoing prospective cohort study which included men who were aged 21 to 80 years at entry. We identified multiple DNA methylation CpG sites that might mediate the effect of smoking on lung function with effect sizes ranging from –0.18 to –0.79 and false discovery rate controlled at the level 0.05, including the CpG sites in the genes AHRR and F2RL3. Our sensitivity analysis found small residual correlations (less than 0.01) of the error terms between the outcome and mediator regressions, suggesting that our results are robust to unmeasured confounding factors. Supplementary materials for this article, including a standardized description of the materials available for reproducing the work, are available as an online supplement.

Individual species and cumulative mixture relationships of 24-hour urine metal concentrations with DNA methylation age variables in older men

BackgroundGlobally, toxic metal exposures are a well-recognized risk factor for many adverse health outcomes. DNA methylation-based measures of biological aging are predictive of disease, but have poorly understood relationships with metal exposures. ObjectiveWe performed a pilot study examining the relationships of 24-h urine metal concentrations with three novel DNA methylation-based measures of biological aging: DNAmAge, GrimAge, and PhenoAge. MethodsWe utilized a previously established urine panel of five common metals [arsenic (As), cadmium (Cd), lead (Pb), manganese (Mn), and mercury (Hg)] found in a subset of the elderly US Veterans Affairs Normative Aging Study cohort (N = 48). The measures of DNA methylation-based biological age were calculated using CpG sites on the Illumina HumanMethylation450 BeadChip. Bayesian Kernel Machine Regression (BKMR) was used to determine metals most important to the aging outcomes and the relationship of the cumulative metal mixture with the outcomes. Individual relationships of important metals with the biological aging outcomes were modeled using fully-adjusted linear models controlling for chronological age, renal function, and lifestyle/environmental factors. ResultsMn was selected as important to PhenoAge. A 1 ng/mL increase in urine Mn was associated with a 9.93-year increase in PhenoAge (95%CI: 1.24, 18.61, p = 0.03). The cumulative urine metal mixture was associated with increases in PhenoAge. Compared to a model where each metal in the mixture is set to its 50th percentile value, every one-unit increase of the cumulative mixture with each metal at its 70th percentile was associated with a 2.53-year increase in PhenoAge (95%CI: 0.10, 4.96, P<0.05). ConclusionOur results add novel evidence that metals detected in urine are associated with increases in biological aging and suggest that these DNA methylation-based measures may be useful for identifying individuals at-risk for diseases related to toxic metal exposures. Further research is necessary to confirm these findings more broadly.

Effect of Dietary Sodium and Potassium Intake on the Mobilization of Bone Lead among Middle-Aged and Older Men: The Veterans Affairs Normative Aging Study

Bone is a major storage site as well as an endogenous source of lead in the human body. Dietary sodium and potassium intake may play a role in the mobilization of lead from bone to the circulation. We examined whether association between bone lead and urinary lead, a marker of mobilized lead in plasma, was modified by dietary intake of sodium and potassium among 318 men, aged 48–93 years, in the Veterans Affairs (VA) Normative Aging Study. Dietary sodium and potassium were assessed by flame photometry using 24-h urine samples, and a sodium-to-potassium ratio was calculated from the resulting measures. Patella and tibia bone lead concentrations were measured by K-shell-x-ray fluorescence. Urinary lead was measured by inductively coupled plasma mass spectroscopy in 24-h urine samples. Linear regression models were used to regress creatinine clearance-corrected urinary lead on bone lead, testing multiplicative interactions with tertiles of sodium, potassium, and sodium-to-potassium ratio, separately. After adjustment for age, body mass index, smoking, vitamin C intake, calcium, and total energy intake, participants in the highest tertile of sodium-to-potassium ratio showed 28.1% (95% CI: 12.5%, 45.9%) greater urinary lead per doubling increase in patella lead, whereas those in the second and lowest tertiles had 13.8% (95% CI: −1.7%, 31.7%) and 5.5% (95% CI: −8.0%, 21.0%) greater urinary lead, respectively (p-for-interaction = 0.04). No statistically significant effect modification by either sodium or potassium intake alone was observed. These findings suggest that relatively high intake of sodium relative to potassium may play an important role in the mobilization of lead from bone into the circulation.

DOES PERSONALITY PREDICT PATTERNS OF AGING? LONGITUDINAL FINDINGS FROM THE VA NORMATIVE AGING STUDY

Previous research using the Veterans Affairs Normative Aging Study identified four patterns of aging using group-based multi-trajectory modelling to identify joint changes in life satisfaction (LS) and functional health (FH) (Nath et al., 2018a,b). The purpose of the present study was to examine whether personality traits predicted these four patterns: impaired (stable low LS and FH), normal (decreasing LS and FH), optimal (high LS, decreasing FH), and successful aging (high LS and FH). The sample consisted of 992 NAS men who provided 3,853 observations (M=2.81, SD=1.54, range 1–8) between 1987 and 2010 (Mage=62.31, SDage=7.50, range 44-86 in 1987). Multinomial logit regression analysis with robust estimation controlled for marital, employment, and self-rated health status, using optimal aging as the reference group. Compared to the optimal aging group, neuroticism predicted membership to the normal aging (RR=1.61, CI=1.16–2.22) and the successful aging groups (RR=.55, CI=.38–.79). Optimism predicted membership to all groups, with lower risk ratios to the impaired aging group (RR=.11, CI=.04–.33) and normal aging group (RR=.57, CI=.42–.79), and higher risk ratio to the optimal aging group (RR=1.96, CI=1.35–2.85). Extraversion only predicted membership in the impaired aging group (RR=.27, CI=.12–.63) indicating high levels of social isolation. Thus, personality may play an important role in determining the patterns of aging.

Effect of Dietary Sodium and Potassium Intake on the Mobilization of Bone Lead among Middle-aged and Older Men

Bone is a major storage site as well as an endogenous source of lead in the human body. Dietary sodium and potassium intake may play a role in the mobilization of lead from bone to the circulation. We examined whether association between bone lead and urinary lead, a marker of mobilized lead in plasma, was modified by dietary intake of sodium and potassium among 318 men, aged 48-93 years, in the Veterans Affairs (VA) Normative Aging Study. Dietary sodium and potassium were assessed by flame photometry using 24-h urine samples, and a sodium-to-potassium ratio was calculated from the resulting measures. Patella and tibia bone lead concentrations were measured by K-shell-x-ray fluorescence. Urinary lead was measured by inductively coupled plasma mass spectroscopy in 24-h urine samples. Linear regression models were used to regress creatinine clearance-corrected urinary lead on bone lead, testing multiplicative interactions with tertiles of sodium, potassium, and sodium-to-potassium ratio, separately. After adjustment for age, body mass index, smoking, vitamin C intake, calcium, and total energy intake, participants in the highest tertile of sodium-to-potassium ratio showed 28.1% (95% CI: 12.5%, 45.9%) greater urinary lead per doubling increase in patella lead, whereas those in the second and lowest tertiles had 13.8% (95% CI: -1.7%, 31.7%) and 5.5% (95% CI: -8.0%, 21.0%) greater urinary lead, respectively (p-for-interaction = 0.04). No statistically significant effect modification by either sodium or potassium intake alone was observed. These findings suggest that relatively high intake of sodium relative to potassium may play an important role in the mobilization of lead from bone into the circulation.

Optimism is not associated with two indicators of DNA methylation aging.

Evidence indicates associations between higher optimism and reduced risk of age-related conditions and premature mortality. This suggests optimism is a positive health asset, but research identifying potential biological mechanisms underlying these associations remains limited. One potential pathway is slower cellular aging, which may delay age-related deterioration in health. Data were from the Women’s Health Initiative (WHI) (N=3,298) and the Veterans Affairs Normative Aging Study (NAS) (N=514), and included dispositional and explanatory style optimism measures. We evaluated whether higher optimism was associated with metrics suggestive of less cellular aging, as indicated by two DNA methylation algorithms, intrinsic (IEAA) and extrinsic epigenetic age acceleration (EEAA); these algorithms represent accelerated biologic aging that exceeds chronological age. We used linear regression models to test our hypothesis while considering several covariates (sociodemographics, depressive symptoms, health behaviors). In both cohorts, we found consistently null associations of all measures of optimism with both measures of DNA methylation aging, regardless of covariates considered. For example, in fully-adjusted models, dispositional optimism was not associated with either IEAA (WHI:β=0.02; 95% Confidence Interval [CI]:-0.15-0.20; NAS:β=-0.06; 95% CI:-0.56-0.44) or EEAA (WHI:β=-0.04; 95% CI: -0.26-0.17; NAS:β=-0.17; 95% CI: -0.80-0.46). Higher optimism was not associated with reduced cellular aging as measured in this study.

Smoking-Related DNA Methylation is Associated with DNA Methylation Phenotypic Age Acceleration: The Veterans Affairs Normative Aging Study.

DNA methylation may play a critical role in aging and age-related diseases. DNA methylation phenotypic age (DNAmPhenoAge) is a new aging biomarker and predictor of chronic disease risk. While smoking is a strong risk factor for chronic diseases and influences methylation, its influence on DNAmPhenoAge is unknown. We investigated associations of self-reported and epigenetic smoking indicators with DNAmPhenoAge acceleration in a longitudinal aging study in eastern Massachusetts. DNA methylation was measured in whole blood samples from multiple visits for 692 male participants in the Veterans Affairs Normative Aging Study during 1999–2013. Acceleration was defined using residuals from linear regression of the DNAmPhenoAge on the chronological age. Cumulative smoking (pack-years) was significantly associated with DNAmPhenoAge acceleration, whereas self-reported smoking status was not. We observed significant validated associations between smoking-related loci and DNAmPhenoAge acceleration for 52 CpG sites, where 18 were hypomethylated and 34 were hypermethylated, mapped to 16 genes. The AHRR gene had the most loci (N = 8) among the 16 genes. We generated a smoking aging index based on these 52 loci, which showed positive significant associations with DNAmPhenoAge acceleration. These epigenetic biomarkers may help to predict age-related risks driven by smoking.

Impact of combat exposure on mental health trajectories in later life: Longitudinal findings from the VA Normative Aging Study.

Cross-sectional studies have shown contradictory results concerning the impact of combat exposure on mental health in later life. We examined whether combat exposure influences trajectories of mental health symptoms in older male veterans using longitudinal data collected from 1985 to 1991 in the Veterans Affairs Normative Aging Study (N = 1,105, age range = 40-86 years in 1985). Noncombat veterans showed little systematic change in depressive and anxiety symptoms with age, whereas combat veterans showed U-shaped nonlinear changes, with higher levels in midlife decreasing until the mid-60s and then increasing again in the 70s and 80s. These findings support the notion that military service, and especially combat exposure, is a hidden variable in aging research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Low-Level Cumulative Lead and Resistant Hypertension: A Prospective Study of Men Participating in the Veterans Affairs Normative Aging Study.

BackgroundBone lead offers a better method over blood lead measurement to discern long‐term lead exposure and accumulation. We examined the risk of resistant hypertension based on bone lead levels in a prospective cohort study of NAS (Normative Aging Study).Methods and ResultsParticipants had clinic data on hypertension (systolic blood pressure, diastolic blood pressure, and antihypertension medication), lead (blood, bone‐patella, bone‐tibia), and demographic and confounding variables. Cases of resistant hypertension were identified by meeting criteria for: (1) inadequate systolic blood pressure (>140 mm Hg) or diastolic blood pressure (>90 mm Hg) while taking 3 medications or (2) requiring >4 medications for blood pressure control. A modified Poisson regression was used for model analysis. Of the 475 participants, 97 cases of resistant hypertension (20.4%) were identified. Among the cases of resistant hypertension, the median tibia and patella lead levels were 20 μg/g and 25 μg/g, respectively, while median tibia and patella lead levels were 20 μg/g and 27.5 μg/g, respectively, in participants without resistant hypertension. Tibia lead demonstrated a significant association with resistant hypertension (relative risk, 1.19; 95% confidence interval, 1.01–1.41 [P=0.04]) per interquartile range increase in tibia lead (13–28.5 μg/g). Patella lead was not associated with resistant hypertension (relative risk, 1.10; 95% confidence interval, 0.92–1.31 [P=0.31]) per interquartile range increase in patella lead (18–40 μg/g). Blood lead levels were not significantly associated with resistant hypertension (relative risk, 1.11; 95% confidence interval, 0.88–1.40 [P=0.38]).ConclusionsTibia lead represents a novel risk factor for resistant hypertension. Our study demonstrates an increased association between tibia lead and resistant hypertension status, with an increased risk of 19% per 1 interquartile range increase in tibia lead.

Extracellular vesicle-enriched microRNAs interact in the association between long-term particulate matter and blood pressure in elderly men

BackgroundSeveral studies have shown that exposure to particulate matter (PM) may lead to increased systemic blood pressure, but the underlying biological mechanisms remain unknown. Emerging evidence shows that extracellular vesicle-enriched miRNAs (evmiRNAs) are associated with PM exposure and cardiovascular risk. In this study, we investigated the role of evmiRNAs in the association between PM and blood pressure, as well as their epigenetic regulation by DNA methylation. MethodsParticipants (n = 22, men) were randomly selected from the Veterans Affairs Normative Aging Study (NAS). Long-term (1-year and 6-month average) PM2.5 exposure was estimated at 1 × 1-km resolution using spatio-temporal prediction models and BC was estimated using validated time varying land use regression models. We analyzed 31 evmiRNAs detected in ≥ 90% of all individuals and for statistical analysis, we used mixed effects models with random intercept adjusted for age, body mass index, smoking, C-reactive protein, platelets, and white blood cells. ResultsWe found that per each 2-standard deviations increase in 6-month PM2.5 ambient levels, there was an increase in 0.19 mm Hg (95% Confidence Interval [95%CI]: 0.11, 0.28 mmHg; p < 0.001) in systolic blood pressure (SBP). Per each 2-standard deviations increase in 1-year PM2.5 levels, there was an increase in 0.11 mm Hg (95% Confidence Interval [95% CI]: 0.03, 0.19 mmHg; p = 0.012) in SBP in older male individuals. We also found that both miR-199a/b (β = 6.13 mmHg; 95% CI: 0.87, 11.39; pinteraction = 0.07) and miR-223–3p (β = 30.17 mmHg; 95% CI: 11.96, 48.39 mmHg; pinteraction = 0.01) modified the association between 1-year PM2.5 and SBP. When exploring DNA methylation as a potential mechanism that could epigenetically regulate expression of evmiRNAs, we found that PM2.5 ambient levels were negatively associated with DNA methylation levels at CpG (cg23972892) near the enhancer region of miR-199a/b (β = −13.11; 95% CI: −17.70, −8.52; pBonferroni< 0.01), but not miR-223-3p. ConclusionsOur findings suggest that expression of evmiRNAs may be regulated by DNA methylation in response to long-term PM2.5 ambient levels and modify the magnitude of association between PM2.5 and systolic blood pressure in older individuals.

Abstract 134: Does Low-Level Cumulative Lead Play a Role in Resistant-Hypertension?

Purpose: Deposition of lead into bone offers a better method over conventional blood lead measurement to discern long-term lead exposure and its insidious accumulation within the body. Bone lead deposition has been identified as an independent risk factor for hypertension (HTN). Yet, little is known how bone lead as a risk factor for HTN can be translated into clinical utility. We examined the association between bone lead levels and resistant-HTN. Methods: All subjects were males, participating in the Veterans Affairs Normative Aging Study (NAS) with an age variation of 48-93 years old. Participants were included if there was complete data on HTN (systolic blood pressure, diastolic blood pressure, and anti-HTN medication), lead (blood, bone-patella, bone-tibia), as well as demographic and confounding variables. Cases of resistant-HTN were identified by meeting criteria for a) inadequate SBP (≥140 mmHg) or DBP (≥90 mmHg) on 3 medications or b) requiring ≥ 4 medications for blood pressure control. Resistant-HTN was categorized as a dichotomous variable, based upon meeting the noted criteria, while tibia and patella bone lead were treated as continuous variables. The data was analyzed using a binomial logistic regression, accounting for demographic and confounding variables. Results: Of the 871 total study participants, 111 cases of resistant-HTN (12.7%) were identified. Amongst the cases of resistant-HTN, the mean tibia and patella lead levels were 23.1 μg/g and 31.5 μg/g, respectively. Both mean levels were higher than those among the participants without resistant-HTN (21.5 μg/g and 30.9 μg/g, respectively). Tibia lead levels demonstrated a significant association with resistant-HTN (OR=1.27 (95% CI, 1.01-1.59) per one IQR increase in tibia lead (15μg/g), p=0.04) after adjusting for age, BMI, cigarette pack-year burden, income, education, and ethnicity. A weak, non-significant association was observed between patella lead and resistant-HTN (OR = 1.16 (95% CI, 0.92-1.46) per one IQR increase in patella lead (21μg/g), p=0.21). Conclusion: Lead has been long-studied for its effect on blood pressure. Yet, lead has not previously been assessed for the role it plays in clinical outcomes. Difficulty in attaining goal blood pressure may be influenced by environmental exposures. Our study demonstrates an increased association between tibia lead and resistant-HTN status, with an OR of 1.27 per one IQR increase in tibia lead. Tibia lead represents a novel risk factor for resistant-HTN. Future research should consider screening and mitigation strategies for populations with resistant-HTN exposed to long-term low-levels of lead.

A Western Diet Pattern Is Associated with Higher Concentrations of Blood and Bone Lead among Middle-Aged and Elderly Men.

Background: Little is known about the effects of overall dietary pattern on lead concentration.Objective: We examined the association of overall dietary patterns, derived from a semiquantitative food frequency questionnaire, with bone and blood lead concentrations.Methods: These longitudinal analyses included mostly non-Hispanic white, middle-aged-to-elderly men from the Veterans Affairs Normative Aging Study. Long-term lead exposures were measured as tibia and patella lead concentrations by using K-shell-X-ray fluorescence. Short-term lead exposures were measured as blood lead concentrations by using graphite furnace atomic absorption spectroscopy. Dietary pattern scores were derived by using factor analysis. Linear mixed-effects models were utilized to predict blood lead concentrations among 983 men, aged 44-92 y at baseline, with a total of 3273 observations (during 1987-2008). We constructed linear regression models to determine the relations between dietary patterns and bone lead concentrations among 649 participants with an age range of 49-93 y.Results: Two major dietary patterns were identified: a prudent dietary pattern, characterized by high intakes of fruit, legumes, vegetables, whole grains, poultry, and seafood; and a Western dietary pattern, characterized by high intakes of processed meat, red meat, refined grains, high-fat dairy products, French fries, butter, and eggs. After adjusting for age, smoking status, body mass index, total energy intake, education, occupation, neighborhood-based education and income level, men in the highest tertile of the Western pattern score (compared with the lowest) had 0.91 μg/dL (95% CI: 0.41, 1.42 μg/dL) higher blood lead, 5.96 μg/g (95% CI: 1.76, 10.16 μg/g) higher patella lead, and 3.83 μg/g (95% CI: 0.97, 6.70 μg/g) higher tibia lead. No significant association was detected with the prudent dietary pattern in the adjusted model.Conclusions: These findings suggest that the Western diet is associated with a greater lead body burden among the middle-aged-to-elderly men. More studies are needed to examine the underlying mechanisms by which dietary patterns are associated with lead concentrations.

Cognitive function and short-term exposure to residential air temperature: A repeated measures study based on spatiotemporal estimates of temperature

Few studies have examined the association between ambient temperature and cognitive function, or used exposure to temperature at a given address instead of a single stationary monitor. The existing literature on the temperature-cognition relationship has mostly consisted of experimental studies that involve a small sample size and a few specific temperature values. In the current study, we examined the association between residential air temperature and Mini-Mental State Examination (MMSE) scores, a quantitative measurement of cognitive function, in a longitudinal cohort of elderly men. Residential air temperature was estimated by a novel spatiotemporal approach that incorporates satellite remote sensing, land use regression, meteorological variables and spatial smoothing in the Northeastern USA. We then applied logistic regression generalized estimating equations to examine the relationship between residential temperature (range: −5.8–25.7°C), and the risk of low MMSE scores (MMSE scores ≤25) among 594 elderly men (1085 visits in total) from the Veterans Affairs Normative Aging Study, 2000–2008. Sensitivity analysis on visits wherein subjects lived within 30km of the clinic center in Massachusetts or aged ≥70 years was also evaluated. A statistically significant, U-shaped association between residential air temperature and low MMSE score (p-value=0.036) was observed. Sensitivity analysis suggested that the estimated effect remains among individuals aged ≥70 years. In conclusion, the data suggest that risk of low MMSE scores is highest when temperature is either high or low, and lowest when ambient temperature is approximately within 10–15°C in a cohort of elderly men. Further research is needed to confirm our findings and assess generalizability to other populations.

Telomere Length, Long-Term Black Carbon Exposure, and Cognitive Function in a Cohort of Older Men: The VA Normative Aging Study.

Background:Long-term air pollution exposure has been associated with age-related cognitive impairment, possibly because of enhanced inflammation. Leukocytes with longer telomere length (TL) are more responsive to inflammatory stimuli, yet TL has not been evaluated in relation to air pollution and cognition.Objectives:We assessed whether TL modifies the association of 1-year exposure to black carbon (BC), a marker of traffic-related air pollution, with cognitive function in older men, and we examined whether this modification is independent of age and of C-reactive protein (CRP), a marker of inflammation.Methods:Between 1999 and 2007, we conducted 1–3 cognitive examinations of 428 older men in the Veterans Affairs (VA) Normative Aging Study. We used covariate-adjusted repeated-measure logistic regression to estimate associations of 1-year BC exposure with relative odds of being a low scorer (≤ 25) on the Mini-Mental State Examination (MMSE), which is a proxy of poor cognition. Confounders included age, CRP, and lifestyle and sociodemographic factors.Results:Each doubling in BC level was associated with 1.57 (95% CI: 1.20, 2.05) times higher odds of low MMSE scores. The BC-MMSE association was greater only among individuals with longer blood TL (5th quintile) (OR = 3.23; 95% CI: 1.37, 7.59; p = 0.04 for BC-by-TL-interaction). TL and CRP were associated neither with each other nor with MMSE. However, CRP modified the BC-MMSE relationship, with stronger associations only at higher CRP (5th quintile) and reference TL level (1st quintile) (OR = 2.68; 95% CI: 1.06, 6.79; p = 0.04 for BC-by-CRP-interaction).Conclusions:TL and CRP levels may help predict the impact of BC exposure on cognitive function in older men.Citation:Colicino E, Wilson A, Frisardi MC, Prada D, Power MC, Hoxha M, Dioni L, Spiro A III, Vokonas PS, Weisskopf MG, Schwartz JD, Baccarelli AA. 2017. Telomere length, long-term black carbon exposure, and cognitive function in a cohort of older men: the VA Normative Aging Study. Environ Health Perspect 125:76–81; http://dx.doi.org/10.1289/EHP241

Dietary anthocyanin intake and age-related decline in lung function: longitudinal findings from the VA Normative Aging Study1–3

Background: It is unknown whether habitual intake of dietary flavonoids, known for their antioxidative and anti-inflammatory properties, affects longitudinal change in lung function.Objective: We investigated whether different flavonoid subclasses present in the habitual diet were associated with beneficial changes in lung function over time in the elderly.Design: This longitudinal analysis included 839 participants from the VA (Veterans Affairs) Normative Aging Study whose lung function [forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC)] was measured at 2 and up to 5 visits between 1992 and 2008 (n = 2623 measurements). Yearly average intake of major flavonoid subclasses (anthocyanins, flavanones, flavan-3-ols, flavonols, flavones, and polymers) was calculated from food-frequency questionnaires at each visit. We estimated adjusted differences in annual change in lung function associated with each flavonoid subclass, categorized into quartiles, in linear mixed-effects regression models after adjustment for lifestyle and dietary confounders.Results: Strong inverse associations were found between anthocyanin intake and age-related decline in lung function. Independent of dietary and nondietary risk factors, slower rates of FEV1 and FVC decline by 23.6 (95% CI: 16.6, 30.7) and 37.3 (95% CI: 27.8, 46.8) mL/y, respectively, were observed in participants in the fourth quartile of intake compared with participants in the first quartile (P-trend < 0.0001). The protective associations observed for anthocyanin intake were present in both current/former and never smokers. Compared with no or very low intakes, an intake of ≥2 servings of anthocyanin-rich blueberries/wk was associated with slower decline in FEV1 and FVC by 22.5 (95% CI: 10.8, 34.2) and 37.9 (95% CI: 22.1, 53.7) mL/y, respectively. To a lesser extent, higher flavan-3-ol intake was also associated with slower lung function decline.Conclusions: An attenuation of age-related lung function decline was associated with higher dietary anthocyanin intake in this longitudinal sample of predominantly elderly men. Further prospective studies are needed to confirm these novel associations.

The effects of daily co-occurrence of affect on older adults’ reactivity to health stressors

Objectives: The present study examined age differences among older adults in the daily co-occurrence of affect and its potential role in buffering the negative effects of health stressors.Design: Participants were from the Veterans Affairs Normative Aging Study and included 249 young-old adults (age = 60–79 years, M = 71.6) and 64 old-old adults (age = 80–89, M = 82.9) who completed questionnaires assessing stressors, physical health symptoms, and positive and negative affect for eight consecutive days.Results: An independent samples t-test showed young-old and old-old adults did not significantly differ in their mean levels of daily co-occurrence of affect. The between-person relationships among stressors, health and daily co-occurrence of affect revealed that neither stressors nor health were significantly related to daily co-occurrence of affect. However, results from a multilevel model revealed a three-way cross-level interaction (health stressor × age group × co-occurrence of affect) where old-old adults with higher levels of co-occurrence of affect were less emotionally reactive to health stressors than young-old adults.Conclusion: These findings provide support for the assertion that co-occurrence of affect functions in an adaptive capacity and highlight the importance of examining domain-specific stressors.