Tibia Lead Research Articles

Cumulative Lead Exposure and Incidence of Age-related Cataract in Older Men

Purpose: Cumulative lead exposure has been suggested as a risk factor for age-related cataract (ARC) A previous study in a cohort of elderly men reported a significant association between cumulative lead exposure and risk of ARC. Here, we extended this analysis and examined new incident cases of ARC in relation to lead exposure. We also evaluated potential effect modification by dietary intake of antioxidant vitamins, calcium and iron. Methods: This study includes ARC-free 632 males (mean age=66.2±6.4 years) from the Normative Aging Study who had tibia and patella lead levels measured by K X-ray fluorescence (KXRF) from 1991 to 1999. Cataract status was graded through Slit Lamp Exam and ARC cases were defined as those who had cataract surgery or were diagnosed as any subtype of cataract grade 3 or higher. Cox proportional hazards model was used to estimate hazard ratio (HR) and 95% confidence interval (CI) of incident ARC. Calorie-adjusted daily intake of iron, calcium, vitamin D, vitamin C, vitamin E and carotenoids were computed and dichotomized at the median (low vs. high) for testing effect modification. Results: Of 632 participants, we identified 208 incident ARC at the end of follow-up (316 cases/10,000 person years). After adjusting for important confounders, tibia lead was significantly associated with incident ARC (HR per interquartile range increase (IQR:15 μg/g) =1.21, 95% CI: 1.05, 1.40, p=0.03). We found a weaker and non-significant association with patella lead (HR per IQR increase (20 μg/g) =1.05, 95% CI: 0.52, 2.11, p=0.11). The association between tibia lead and ARC was stronger in people with lower carotene intake and higher intake of vitamins C, D and E and iron and calcium but the interaction terms were not statistically significant . Conclusions: Our findings reinforce that cumulative lead exposure is an important risk factor for ARC. We found no consistent patterns in effect modification by nutrients.

APOE ε4 allele modifies the association of lead exposure with age-related cognitive decline in older individuals

BackgroundContinuing 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. MethodsWe 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. ResultsAn 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. ConclusionsOur findings suggest that individuals carrying both ε4 alleles are more susceptible to lead impact on global cognitive decline during aging.

Altered miRNA expression in the cervix during pregnancy associated with lead and mercury exposure.

Toxic metals including lead and mercury are associated with adverse pregnancy outcomes. This study aimed to assess the association between miRNA expression in the cervix during pregnancy with lead and mercury levels. We obtained cervical swabs from pregnant women (n = 60) and quantified cervical miRNA expression. Women's blood lead, bone lead and toenail mercury levels were analyzed. We performed linear regression to examine the association between metal levels and expression of 74 miRNAs adjusting for covariates. Seventeen miRNAs were negatively associated with toenail mercury levels, and tibial bone lead levels were associated with decreased expression of miR-575 and miR-4286. The findings highlight miRNAs in the human cervix as novel responders to maternal chemical exposure during pregnancy.

Cumulative lead exposure is associated with reduced olfactory recognition performance in elderly men: The Normative Aging Study

IntroductionOlfactory dysfunction has been identified as an early warning sign for Alzheimer's disease, Parkinson's disease, dementia and more. A few occupational and environmental exposures have also been associated with reduced olfactory function, although the effects of long term environmental exposure to lead on olfactory dysfunction have not been explored. Here we performed olfactory recognition testing in elderly men in a community-dwelling cohort and examined the association with cumulative lead exposure, as assessed by lead in tibial and patellar bone. MethodsOlfactory recognition was measured in 165 men from the Normative Aging Study (NAS) who had previously taken part in bone lead measurements using K-X-ray fluorescence (KXRF). Olfactory recognition was measured using the University of Pennsylvania Smell Identification Test (UPSIT). Associations between olfactory recognition, global cognition and cumulative lead exposure were estimated using linear regression, with additional adjustment for age, smoking, and functional polymorphism status for hemochromatosis (HFE), transferrin (TfC2), glutathione-s-transferase Pi1 (GSTP1) and apolipoprotein E (APOE) genotypes. Sensitivity analyses explored olfactory recognition in men with high global cognitive function as measured using the Mini-Mental Status Exam (MMSE). ResultsThe average age of the NAS participants at the time of olfactory recognition testing was 80.3 (standard deviation or SD=5.7) years. Mean tibia lead was 16.3 (SD=12.0)μg/g bone, mean patella lead was 22.4 (SD=14.4)μg/g bone, and mean UPSIT score was 26.9 out of 40 (SD=7.0). Consistent with previous findings, age at olfaction testing was negatively associated with UPSIT score. Tibia (but not patella) bone lead was negatively associated with olfaction recognition (per 15μg/g tibia lead: β=−1.57; 95% CI: −2.93, −0.22; p=0.02) in models adjusted for smoking and age. Additional adjustment for education did not significantly change results. Of all the genes explored, only the presence of one or more HFE variant alleles was significantly associated with olfaction recognition (HFE β=2.26; 95% CI: 0.09, 4.43; p=0.04). In a model containing the HFE term and a lead term, the tibia lead parameter estimate dropped by 21% (per 15μg/g tibia lead: β=−1.25; 95% CI: −2.64, 0.14; p=0.08) while the HFE term dropped 15% (β=1.91; 95% CI: −0.28, 4.10; p=0.09). None of the other gene terms were associated with olfactory recognition in this cohort, nor were any gene–lead interaction terms significant. Additional sensitivity analysis in men with MMSE scores of 25 or higher (n=149) showed a similar but slightly attenuated association between lead and olfactory recognition (per 15μg/g tibia lead β=−1.39; 95% CI: −3.00, 0.22; p=0.09). ConclusionCumulative exposure to lead is associated with reduced olfactory recognition in a cohort of elderly men. The association was similar but not significant in men with better cognitive function as measured by the MMSE. Iron metabolism gene status may also affect olfactory function.

Prenatal Lead Exposure Modifies the Impact of Maternal Self-Esteem on Children's Inattention Behavior

To prospectively evaluate the association of maternal self-esteem measured when their offspring were toddlers with the subsequent development of attention deficit hyperactivity disorder (ADHD)-like behavior in their school-age offspring and the potential modifying effects of prenatal lead exposure. We evaluated a subsample of 192 mother-child pairs from a long-running birth-cohort project that enrolled mothers in Mexico from 1994-2011. Prenatal lead exposure was assessed using cord blood lead and maternal bone lead around delivery (tibia and patella lead, measured by K-x-ray-fluorescence). When children were 2 years old, maternal self-esteem was measured using the Coopersmith Self-Esteem Inventory. When children were 7-15 years old, children's blood lead levels and ADHD symptoms were assessed, and Conners' Parent Rating Scale-Revised and Behavior Rating Inventory of Executive Function-Parent Form were used as measures of ADHD-like behavior. Adjusting for family economic status, marital status, maternal education and age, child's age and sex, and children's current blood lead levels, increased maternal self-esteem was associated with reduced child inattention behavior. Compared with those among high prenatal lead exposure (P25-P100), this association was stronger among low prenatal lead exposure groups (P1-P25, P values for the interaction effects between prenatal lead exposure and maternal self-esteem levels of <.10). Each 1-point increase in maternal self-esteem scores was associated with 0.6- to 1.3-point decrease in Conners' Parent Rating Scale-Revised and Behavior Rating Inventory of Executive Function-Parent Form T-scores among groups with low cord blood lead and patella lead (P1-P25). Children experiencing high maternal self-esteem during toddlerhood were less likely to develop inattention behavior at school age. Prenatal lead exposure may play a role in attenuating this protective effect.

Lead exposure and tremor among older men: the VA normative aging study.

Background: Tremor is one of the most common neurological signs, yet its etiology is poorly understood. Case–control studies suggest an association between blood lead and essential tremor, and that this association is modified by polymorphisms in the δ-aminolevulinic acid dehydrogenase (ALAD) gene.Objective: We aimed to examine the relationship between lead and tremor, including modification by ALAD, in a prospective cohort study, using both blood lead and bone lead—a biomarker of cumulative lead exposure.Methods: We measured tibia (n = 670) and patella (n = 672) bone lead and blood lead (n = 807) among older men (age range, 50–98 years) in the VA Normative Aging Study cohort. A tremor score was created based on an approach using hand-drawing samples. ALAD genotype was dichotomized as ALAD-2 carriers or not. We used linear regression adjusted for age, education, smoking, and alcohol intake to estimate the associations between lead biomarkers and tremor score.Results: In unadjusted analyses, there was a marginal association between quintiles of all lead biomarkers and tremor scores (p-values < 0.13), which did not persist in adjusted models. Age was the strongest predictor of tremor. Among those younger than the median age (68.9 years), tremor increased significantly with blood lead (p = 0.03), but this pattern was not apparent for bone lead. We did not see modification by ALAD or an association between bone lead and change in tremor score over time.Conclusion: Our results do not strongly support an association between lead exposure and tremor, and suggest no association with cumulative lead biomarkers, although there is some suggestion that blood lead may be associated with tremor among the younger men in our cohort.Citation: Ji JS, Power MC, Sparrow D, Spiro A III, Hu H, Louis ED, Weisskopf MG. 2015. Lead exposure and tremor among older men: the VA Normative Aging Study. Environ Health Perspect 123:445–450; http://dx.doi.org/10.1289/ehp.1408535

Effect modification by vitamin D receptor genetic polymorphisms in the association between cumulative lead exposure and pulse pressure: a longitudinal study.

BackgroundAlthough the association between lead and cardiovascular disease is well established, potential mechanisms are still poorly understood. Calcium metabolism plays a role in lead toxicity and thus, vitamin D receptor (VDR) polymorphisms have been suggested to modulate the association between lead and health outcomes. We investigated effect modification by VDR genetic polymorphisms in the association between cumulative lead exposure and pulse pressure, a marker of arterial stiffness.MethodsWe examined 727 participants (3,100 observations from follow-ups from 1991 to 2011) from the Normative Aging Study (NAS), a longitudinal study of aging. Tibia and patella bone lead levels were measured using K-x-ray fluorescence. Four single nucleotide polymorphisms (SNPs) in the VDR gene, Bsm1, Taq1, Apa1, and Fok1, were genotyped. Linear mixed effects models with random intercepts were implemented to take into account repeated measurements.ResultsAdjusting for potential confounders, pulse pressure was 2.5 mmHg (95% CI: 0.4-4.7) and 1.9 mmHg (95% CI: 0.1-3.8) greater per interquartile range (IQR) increase in tibia lead (15 μg/g) and patella lead (20 μg/g), respectively, in those with at least one minor frequency allele in Bsm1 compared with those with major frequency allele homozygotes. The observed interaction effect between bone lead and the Bsm1 genotype persists over time during the follow-up. Similar results were observed in effect modification by Taq1.ConclusionsThis study suggests that subjects with the minor frequency alleles of VDR Bsm1 or Taq1 may be more susceptible to cumulative lead exposure-related elevated pulse pressure.Electronic supplementary materialThe online version of this article (doi:10.1186/1476-069X-14-5) contains supplementary material, which is available to authorized users.

Physiologically based modeling of lead kinetics: a pilot study using data from a Canadian population.

The Canadian population is currently subject to low, chronic lead exposure and an understanding of its effects is of great significance to the population's health. Such low exposure is difficult to measure directly; approximation by physiologically based modeling may provide a preferable approach to population analysis. The O'Flaherty model of lead kinetics is based on an age-dependent approach to human growth and development and devotes special attention to bone turnover rates. Because lead is a bone-seeking element, the model was deemed ideal for such an analysis. Sample from 263 individuals of various ages from the Greater Toronto Area were selected to evaluate the applicability of the current version of the O'Flaherty model to populations with low lead exposure. For each individual, the input value of lead exposure was calibrated to match the output value of cortical bone lead to the individual's measured tibia lead concentration; the outputs for trabecular bone, blood, and plasma lead concentrations obtained from these calibrations were then compared with the subjects' measured calcaneus, blood, and serum lead concentrations, respectively. This indicated a need for revision of the model parameters; those for lead binding in blood and lead clearance from blood to bone were adjusted and new outputs were obtained in the same fashion as before. Model predictions of trabecular lead concentration did not agree with measurements in the calcaneus. The outputs for blood and plasma lead concentrations were highly scattered and, on an individual level, inconsistent with corresponding measurements; however, the general trends of the outputs matched those of the measurements reasonably well, which indicates that the revised blood lead binding and lead clearance parameters may be useful in future studies. Overall, the analysis showed that with the revisions to the model discussed here, the model should be a useful tool in the analysis of human lead kinetics and body burden in populations characterized by low, chronic exposure to lead from the general environment.

Modification of the association between lead exposure and amyotrophic lateral sclerosis by iron and oxidative stress related gene polymorphisms

Our objective was to examine whether functional polymorphisms in hemochromatosis (HFE; H63D and C282Y), transferrin (TfC2), and glutathione-s-transferase Pi1 (GSTP1; Ile105Val) genes modify any lead-ALS association. We measured blood lead using atomic absorption spectroscopy and bone lead – a biomarker of cumulative lead exposure – using K-shell-X-ray fluorescence in 100 neurologist-confirmed ALS cases and 194 controls, the latter recruited as part of two separate studies; all subjects lived in New England. Participants were considered variant carriers or wild-type for each polymorphism. To assess effect modification, we included cross-product terms between lead biomarkers and each polymorphism in separate adjusted polytomous logistic regression models. Compared with wild-type, the odds ratio (OR) per 15.6 μg/g patella lead (interquartile range; IQR) was 8.24 (95% CI 0.94–72.19) times greater among C282Y variant carriers, and 0.34 (95% CI 0.15–0.78) times smaller among H63D variant carriers. Results were weaker for tibia lead. Compared with wild-type the OR per 2 μg/dl blood lead (IQR) was 0.36 (95% CI 0.19–0.68) times smaller among H63D variant carriers, and 1.96 (95% CI 0.98–3.92) times greater among GSTP1 variant carriers. In conclusion, we found that HFE and GSTP1 genotypes modified the association between lead biomarkers and ALS. Contrasting modification by the HFE polymorphisms H63D and C282Y may suggest that the modification is not simply the result of increased iron.

Cumulative Lead Exposure and Age at Menopause in the Nurses’ Health Study Cohort

Background: Early menopause has been associated with many adverse health outcomes, including increased risk of cardiovascular disease morbidity and mortality. Lead has been found to be adversely associated with female reproductive function, but whether exposures experienced by the general population are associated with altered age at menopause has not been explored.Objective: Our goal was to assess the association between cumulative lead exposure and age at natural menopause.Methods: Self-reported menopausal status and bone lead concentration measured with K-shell X-ray fluorescence—a biomarker of cumulative lead exposure—were obtained from 434 women participants in the Nurses’ Health Study.Results: The mean (± SD) age at natural menopause was 50.8 ± 3.6 years. Higher tibia lead level was associated with younger age at menopause. In adjusted analyses, the average age of menopause for women in the highest tertile of tibia lead was 1.21 years younger (95% CI: –2.08, –0.35) than for women in the lowest tertile (p-trend = 0.006). Although the number of cases was small (n = 23), the odds ratio for early menopause (< 45 years of age) was 5.30 (95% CI: 1.42, 19.78) for women in the highest tertile of tibia lead compared with those in the lowest tertile (p-trend = 0.006). There was no association between patella or blood lead and age at menopause.Conclusions: Our results support an association between low-level cumulative lead exposure and an earlier age at menopause. These data suggest that low-level lead exposure may contribute to menopause-related health outcomes in older women through effects on age at menopause.Citation: Eum KD, Weisskopf MG, Nie LH, Hu H, Korrick SA. 2014. Cumulative lead exposure and age at menopause in the Nurses’ Health Study Cohort. Environ Health Perspect 122:229–234; http://dx.doi.org/10.1289/ehp.1206399

Cumulative Lead Exposure and Age-Related Cataract in Middle-Aged and Elderly Women

Background: Age-related cataract is the leading cause of blindness and visual impairment worldwide, accounting for more than 40% of global blindness. Lead has been proposed as a potentially important risk factor. Possible mechanisms include lead-induced changes in the lens through redox status, glutathione metabolism, lipid peroxidation, post-translational protein modification, and calcium homeostasis. However, only one epidemiologic study has examined the association between cumulative lead exposure and age-related cataract and it was limited to men. Aim: We examined the association of cumulative lead exposure with the risk of age-related cataract in middle-aged and elderly women. Methods: Participants were 502 Boston area participants in the Nurses' Health Study (mean age=63 yrs, range 55-74 yrs) who had lead exposure assessments done in two substudies (bone lead measured in 1993-1995 and 2001-2004), had cataract extraction from 5 years before the bone lead measurement to 2008, and whose cataracts were not congenital or secondary to chronic steroid use, previous intraocular surgery or ocular trauma. We identified cases of cataract extraction by a biennial questionnaire and confirmed all cases with review of medical records. Bone lead levels were measured by K-x-ray fluorescence. We used logistic regression to compute the odds ratio (OR) and 95% confidence interval (CI) for an interquartile range (IQR) increase in bone lead. Results: We identified 48 cases (9.6%) of cataract extraction. After controlling for substudy, age, smoking, and body mass index, neither bone lead measure was associated with cataract (OR=0.80 (95% CI, 0.51, 1.24) for tibia lead (IQR=11 µg/g); OR=0.98 (95% CI, 0.62, 1.53) for patella lead (IQR=13 µg/g). Conclusions: The present study does not support the hypothesis that cumulative lead exposure increases the risk of age-related cataract in women, but further research in larger populations is needed.

Modifying roles of glutathione S-transferase polymorphisms on the association between cumulative lead exposure and cognitive function

BackgroundGlutathione-S-transferase gene (GST) polymorphisms can result in variable ability of these enzymes to remove electrophilic substrates. We investigated whether the GSTP1 Val105 and GSTM1 deletion polymorphisms modify the lead-cognitive function association. MethodsWe used repeated measures analysis to compare the association between cumulative lead biomarkers—bone lead measured using K-shell X-Ray Fluorescence—and Mini-Mental State Exam (MMSE) score by GST variants, adjusted for covariates, among Normative Aging Study participants, a Boston-based prospective cohort of men. We had complete data for 698 men (providing 1292 observations) for GSTM1 analyses and 595 men (providing 1142 observations) for GSTP1 analyses. ResultsA 15μg/g higher tibia lead concentration (interquartile range of tibia lead) was associated with a 0.24 point decrement in MMSE score among GSTP1 Val105 variant carriers, which was significantly stronger than the association among men with only wild-type alleles (p=0.01). The association among GSTP1 Val105 carriers was comparable to that of 3 years of age in baseline MMSE scores. The association between tibia lead and MMSE score appeared progressively steeper in participants with increasingly more GSTP1 Val105 alleles. A modest association between tibia lead and lower MMSE score was seen among participants with the GSTM1 deletion polymorphism. Neither of the glutathione S-transferase variants was independently associated with cognitive function, nor with lead biomarker measures. The results pertaining to patella lead were similar to those observed for tibia lead. ConclusionOur results suggest that the GSTP1 Val105 polymorphism confers excess susceptibility to the cognitive effects of cumulative lead exposure.

Tibial Bone Lead, but Not Serum Polychlorinated Biphenyl, Concentrations Are Associated With Neurocognitive Deficits in Former Capacitor Workers

To determine the relationships between tibial bone lead and serum polychlorinated biphenyl (PCB) concentrations and neurocognitive function. The study population consisted of men and women former capacitor workers had been employed by the General Electric Corporation between 1946 and 1977. Regression analyses evaluated the association between neurocognitive function and lipid-adjusted serum PCB and tibia lead concentrations. Tibia lead, but not serum PCBs, was significantly correlated with deficits in neurocognitive function. Women showed more associations between tibia lead and neurocognitive function than men, especially regarding executive function. These results demonstrate that low levels of tibia lead, but not serum PCBs, are associated with neurocognitive deficits and that postmenopausal women show a greater number of deficits in executive function than men.

Cumulative exposure to lead and cognition in persons with Parkinson's disease

Dementia is an important consequence of Parkinson's disease (PD), with few known modifiable risk factors. Cumulative exposure to lead, at levels experienced in the community, may exacerbate PD-related neural dysfunction, resulting in impaired cognition. Among 101 persons with PD ("cases") and, separately, 50 persons without PD ("controls"), we evaluated cumulative lead exposure, gauged by tibia and patella bone lead concentrations, in relation to cognitive function, assessed using a telephone battery developed and validated in a separate sample of PD patients. We also assessed the interaction between lead and case-control status. After multivariable adjustment, higher tibia bone lead concentration among PD cases was associated with worse performance on all of the individual telephone tests. In particular, tibia lead levels corresponded to significantly worse performance on a telephone analog of the Mini-Mental State Examination and tests of working memory and attention. Moreover, higher tibia bone lead concentration was associated with significantly worse global composite score encompassing all the cognitive tests (P = 0.04). The magnitude of association per standard deviation increment in tibia bone lead level was equivalent to the difference in global scores among controls in our study, who were approximately 7 years apart in age. The tibia lead-cognition association was notably stronger within cases than within controls (P(difference) = 0.06). Patella bone lead concentration was not consistently associated with performance on the tests. These data provide evidence suggesting that cumulative exposure to lead may result in worsened cognition among persons with PD.

Relation of Cumulative Low-Level Lead Exposure to Depressive and Phobic Anxiety Symptom Scores in Middle-Age and Elderly Women

Background: Different lines of evidence suggest that low-level lead exposure could be a modifiable risk factor for adverse psychological symptoms, but little work has explored this relation.Objective: We assessed whether bone lead—a biomarker of cumulative lead exposure—is associated with depression and anxiety symptoms among middle-age and elderly women.Methods: Participants were 617 Nurses’ Health Study participants with K-shell X-ray fluorescence bone lead measures and who had completed at last one Mental Health Index 5-item scale (MHI-5) and the phobic anxiety scale of the Crown-Crisp Index (CCI) assessment at mean ± SD age of 59 ± 9 years (range, 41–83 years). With exposure expressed as tertiles of bone lead, we analyzed MHI-5 scores as a continuous variable using linear regression and estimated the odds ratio (OR) of a CCI score ≥ 4 using generalized estimating equations.Results: There were no significant associations between lead and either outcome in the full sample, but associations were found among premenopausal women and women who consistently took hormone replacement therapy (HRT) between menopause and bone lead measurement (n = 142). Compared with women in the lowest tertile of tibia lead, those in the highest scored 7.78 points worse [95% confidence interval (CI): –11.73, –3.83] on the MHI-5 (p-trend = 0.0001). The corresponding OR for CCI ≥ 4 was 2.79 (95% CI: 1.02, 7.59; p-trend = 0.05). No consistent associations were found with patella lead.Conclusions: These results provide support for an association of low-level cumulative lead exposure with increased depressive and phobic anxiety symptoms among older women who are premenopausal or who consistently take postmenopausal HRT.

Childhood and Adult Socioeconomic Position, Cumulative Lead Levels, and Pessimism in Later Life: The VA Normative Aging Study

Pessimism, a general tendency toward negative expectancies, is a risk factor for depression and also heart disease, stroke, and reduced cancer survival. There is evidence that individuals with higher lead exposure have poorer health. However, low socioeconomic status (SES) is linked with higher lead levels and greater pessimism, and it is unclear whether lead influences psychological functioning independently of other social factors. The authors considered interrelations among childhood and adult SES, lead levels, and psychological functioning in data collected on 412 Boston area men between 1991 and 2002 in a subgroup of the VA Normative Aging Study. Pessimism was measured by using the Life Orientation Test. Cumulative (tibia) lead was measured by x-ray fluorescence. Structural equation modeling was used to quantify the relations as mediated by childhood and adult SES, controlling for age, health behaviors, and health status. An interquartile range increase in lead quartile was associated with a 0.37 increase in pessimism score (P < 0.05). Low childhood and adult SES were related to higher tibia lead levels, and both were also independently associated with higher pessimism. Lead maintained an independent association with pessimism even after childhood and adult SES were considered. Results demonstrate an interrelated role of lead burden and SES over the life course in relation to psychological functioning in older age.

Association between Prenatal Lead Exposure and Blood Pressure in Children

Background: Lead exposure in adults is associated with hypertension. Altered prenatal nutrition is associated with subsequent risks of adult hypertension, but little is known about whether prenatal exposure to toxicants, such as lead, may also confer such risks.Objectives: We investigated the relationship of prenatal lead exposure and blood pressure (BP) in 7- to 15-year-old boys and girls.Methods: We evaluated 457 mother–child pairs, originally recruited for an environmental birth cohort study between 1994 and 2003 in Mexico City, at a follow-up visit in 2008–2010. Prenatal lead exposure was assessed by measurement of maternal tibia and patella lead using in vivo K-shell X-ray fluorescence and cord blood lead using atomic absorption spectrometry. BP was measured by mercury sphygmomanometer with appropriate-size cuffs.Results: Adjusting for relevant covariates, maternal tibia lead was significantly associated with increases in systolic BP (SBP) and diastolic BP (DBP) in girls but not in boys (p-interaction with sex = 0.025 and 0.007 for SBP and DBP, respectively). Among girls, an interquartile range increase in tibia lead (13 μg/g) was associated with 2.11-mmHg [95% confidence interval (CI): 0.69, 3.52] and 1.60-mmHg (95% CI: 0.28, 2.91) increases in SBP and DBP, respectively. Neither patella nor cord lead was associated with child BP.Conclusions: Maternal tibia lead, which reflects cumulative environmental lead exposure and a source of exposure to the fetus, is a predisposing factor to higher BP in girls but not boys. Sex-specific adaptive responses to lead toxicity during early-life development may explain these differences.

RELATION OF CHRONIC ENVIRONMENTAL LEAD EXPOSURE TO DEPRESSION AND ANXIETY SYMPTOMS IN OLDER WOMEN

Background and Aims: Environmental lead exposure has been associated with adverse cardiovascular and cognitive outcomes, which are themselves correlated with psychological symptoms. Yet few studies have examined links between lead exposure and psychological symptoms. We explored the association between bone lead—a biomarker of cumulative lead exposure—and depression and anxiety symptoms among older women. Methods: We measured patella and tibia bone lead by K-X-Ray-Fluorescence, and obtained repeated measures of depression and anxiety symptoms using the Mental Health Index 5-item subscale (MHI-5) and Crown-Crisp Index phobic anxiety scale (CCI) in 615 women in the Nurses Health Study. We analyzed MHI scores as a continuous variable using linear regression and estimated the odds of a CCI score ≥4 using generalized estimating equations, in both cases accounting for correlation between repeated outcomes (MHI: 3; CCI: 2) and adjusting for potential confounders. Results: The average age of participants was 61 (sd=6) years at the time of bone lead measurement. While tibia lead was associated with moderately worse MHI-5 and CCI scores among all women, results were much stronger among women who, at bone lead measurement, were premenopausal or had been consistently on hormone replacement therapy (HRT) since menopause. In these analyses, women in the highest tibia lead tertile scored 8.16 points worse (95% CI: -11.60, -4.72; p-trend&lt;0.0001) on the MHI-5 than women in the lowest tertile, and had increased odds of high phobic anxiety (CCI ≥4; OR=2.41; 95% CI: 1.06-5.50; p-trend=0.04). We found no relation of patella lead to depression and anxiety symptoms. Conclusions: Our results support an association of cumulative environmental lead exposure with increased risk of depression and anxiety symptoms among older women. Weaker results when including women not consistently on HRT after menopause may be an artifact of increased error in estimating cumulative exposure with bone lead among these women.

Longitudinal Changes in Bone Lead Levels

Bone lead is a cumulative measure of lead exposure that can also be remobilized. We examined repeated measures of bone lead over 11 years to characterize long-term changes and identify predictors of tibia and patella lead stores in an elderly male population. Lead was measured every 3 to 5 years by k-x-ray fluorescence and mixed-effect models with random effects were used to evaluate change over time. A total of 554 participants provided up to four bone lead measurements. Final models predicted a -1.4% annual decline (95% CI: -2.2 to -0.7) for tibia lead and piecewise linear model for patella with an initial decline of 5.1% per year (95% CI: -6.2 to -3.9) during the first 4.6 years but no significant change thereafter (-0.4% [95% CI: -2.4 to 1.7]). These results suggest that bone lead half-life may be longer than previously reported.

Prenatal Lead Exposure and Weight of 0- to 5-Year-Old Children in Mexico City

Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood.Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children’s attained weight over time from birth to 5 years of age.Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City.Results: After controlling for breast-feeding duration, maternal anthropometry, and sociodemographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9-g decrease in weight [95% confidence interval (CI), –227.4 to –34.4 g] among females and a 13.0-g nonsignificant increase in weight among males (95% CI, –73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years.Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies.