Search

Abstract: Background: Pediatric lead (Pb) exposure impacts cognitive function and behavior and co-exposure to manganese (Mn) may enhance neurotoxicity. Objectives: To assess cognitive and behavioral function in adolescents with environmental exposure to Pb and Mn. Methods: In this cross sectional study, cognitive function and behavior were examined in healthy adolescents with environmental exposure to metals. The Wechsler Intelligence Scale for Children (WISC) and the Conners-Wells’ Adolescent Self-Report Scale Long Form (CASS:L) were used to assess cognitive and behavioral function, respectively. ALAD polymorphisms rs1800435 and rs1139488 were measured as potential modifiers. Results: We examined 299 adolescents (49.2% females) aged 11–14 years. Blood lead (BPb) averaged 1.71μg/dL (median 1.5, range 0.44–10.2), mean Blood Manganese (BMn) was 11.1μg/dL (median 10.9, range 4.00–24.1). Average total IQ was 106.3 (verbal IQ=102, performance IQ=109.3). According to a multiple regression model considering the effect of other covariates, a reduction of about 2.4 IQ points resulted from a two-fold increase of BPb. The Benchmark Level of BPb associated with a loss of 1 IQ-point (BML01) was 0.19μg/dL, with a lower 95% confidence limit (BMLL01) of 0.11μg/dL. A very weak correlation resulted between BPb and the ADHD-like behavior (Kendall''s tau rank correlation=0.074, p=0.07). No influence of ALAD genotype was observed on any outcome. Manganese was not associated with cognitive and behavioral outcomes, nor was there any interaction with lead. Conclusions: These findings demonstrate that very low level of lead exposure has a significant negative impact on cognitive function in adolescent children. Being an essential micro-nutrient, manganese may not cause cognitive effects at these low exposure levels. [Copyright &y& Elsevier]

Background Manganese (Mn) is an essential element that can become neurotoxic through various exposure windows over the lifespan. While there is clear evidence of Mn neurotoxicity in pediatric and adult occupational populations, little is known about effects in the elderly who may exhibit enhanced susceptibilities due to compromised physiology compared to younger adults. In the province of Brescia, Italy, the Valcamonica area has been the site of three ferroalloy plants operating from 1902 to 2001. Metal emissions of Mn and to a lesser extent lead (Pb) have impacted the surrounding environment, where a high prevalence of Parkinsonism was previously observed. This study aimed to assess neurocognitive and motor functions in healthy elderly subjects residing for most of their lifetime in Valcamonica or in a reference area unimpacted by ferroalloy plant activity. Methods Subjects were enrolled for extensive neurobehavioral assessment of motor, cognitive and sensory functions. Exposure was assessed with 24 h personal air sampling for PM10 airborne particles, surface soil and tap water measurement at individual households, Mn levels in blood and urine and Pb in blood. Dose–response relationships between exposure indicators and biomarkers and health outcomes were analyzed with generalized (linear and logistic) additive models (GAM). Results A total of 255 subjects (55% women) were examined; most (52.9%) were within the 65–70 years age class. Average airborne Mn was 26.41 ng/m 3 (median 18.42) in Valcamonica and 20.96 ng/m 3 (median 17.62) in the reference area. Average Mn in surface soil was 1026 ppm (median 923) in Valcamonica and 421 ppm (median 410) in the reference area. Manganese in drinking water was below the LDL of 1 μg/L. The GAM analysis showed significant association between airborne Mn ( p = 0.0237) and the motor coordination tests of the Luria Nebraska Neuropsychological Battery. The calculation of the Benchmark Dose using this dose–response relationship yielded a lower level confidence interval of 22.7 ng/m 3 (median 26.4). For the odor identification score of the Sniffin Stick test, an association was observed with soil Mn ( p = 0.0006) and with a significant interaction with blood Pb ( p = 0.0856). Significant dose–responses resulted also for the Raven's Colored Progressive Matrices with the distance from exposure point source ( p = 0.0025) and Mn in soil ( p = 0.09), and for the Trail Making test, with urinary Mn ( p = 0.0074). Serum prolactin (PRL) levels were associated with air ( p = 0.061) and urinary ( p = 0.003) Mn, and with blood Pb ( p = 0.0303). In most of these associations age played a significant role as an effect modifier. Conclusion Lifelong exposure to Mn was significantly associated with changes in odor discrimination, motor coordination, cognitive abilities and serum PRL levels. These effects are consistent with the hypothesis of a specific mechanism of toxicity of Mn on the dopaminergic system. Lead co-exposure, even at very low levels, can further enhance Mn toxicity. [ABSTRACT FROM AUTHOR]

Abstract: Background and objective: Increased prevalence of Parkinsonism was observed in Valcamonica, Italy, a region impacted by ferroalloy plants emissions containing manganese and other metals for a century until 2001. The aim of this study was to assess neurobehavioral functions in adolescents from the impacted region and the reference area of Garda Lake. Methods: Adolescents age 11–14 years were recruited through the school system for neuro-behavioral testing. Metals including manganese, lead, iron, zinc, copper were measured in airborne particulate matter collected with 24-h personal samplers, and in soil, tap water, blood, urine and hair. Independent variables included parental education and socio-economic status, children''s body mass index, number of siblings, parity order, smoking and drinking habits. Results: A total of 311 subjects (49.2% females), residing in either the exposed (n =154) or the reference (n =157) area participated. Average airborne and soil manganese were respectively 49.5ng/m3 (median 31.4, range 1.24–517) and 958ppm (median 897, range 465–1729) in the impacted area, and 27.4ng/m3 (median 24.7, range 5.3–85.9) ng/m3 and 427ppm (median 409 range 160–734) in the reference area. Regression models showed significant impairment of motor coordination (Luria-Nebraska test, p =0.0005), hand dexterity (Aiming Pursuit test, p =0.0115) and odor identification (Sniffin’ task, p =0.003) associated with soil manganese. Tremor intensity was positively associated with blood (p =0.005) and hair (p =0.01) manganese. Conclusion: Historical environmental exposure to manganese from ferroalloy emission reflected by the concentration in soil and the biomarkers was associated with sub-clinical deficits in olfactory and motor function among adolescents. [Copyright &y& Elsevier]

Neurodevelopmental disorders are constantly increasing on a global scale. Some elements like heavy metals are known to be neurotoxic. In this cross-sectional study we assessed the neurobehavioral effect of the exposure to trace elements including lead, mercury, cadmium, manganese, arsenic and selenium and their interactions among 299 schoolchildren residing in the heavily polluted Taranto area in Italy. Whole blood, urine and hair were collected for metal analyses, while the Child Behavior Checklist and the Social Responsiveness Scale, administered to the main teacher and the mothers were considered to identify behavioral problems in children. Blood lead mainly influenced social problems, aggressive behavior, externalizing and total problems. Urinary arsenic showed an impact on anxiety and depression, somatic problems, attention problems and rule breaking behavior. A significant interaction between lead and arsenic was observed, with a synergistic effect of the two metals increasing the risk of attention problems, aggressive behavior, externalizing problems and total problems. Overall, we were able to test that higher blood lead, urinary arsenic concentrations and their interaction increase the risk of neurobehavioral problems. This is in line with the U.S. Environmental Protection Agency's priority list of hazardous substances where arsenic and lead are ranked as first and second respectively. [ABSTRACT FROM AUTHOR]

BACKGROUND: Research on the health effects of chemical mixtures has focused mainly on early life rather than adolescence, a potentially important developmental life stage. OBJECTIVES: We examined associations of a metal mixture with general cognition in a cross-sectional study of adolescents residing near ferromanganese industry, a source of airborne metals emissions. METHODS: We measured manganese (Mn), lead (Pb), copper (Cu), and chromium (Cr) in hair, blood, urine, nails, and saliva from 635 Italian adolescents 10–14 years of age. Full-scale, verbal, and performance intelligence quotient (FSIQ, VIQ, PIQ) scores were assessed using the Wechsler Intelligence Scale for Children-III. Multivariable linear regression and Bayesian kernel machine regression (BKMR) were used to estimate associations of the metal mixture with IQ. In secondary analyses, we used BKMR’s hierarchical variable selection option to inform biomarker selection for Mn, Cu, and Cr. RESULTS: Median metal concentrations were as follows: hair Mn, 0.08 µg/g; hair Cu, 9.6 µg/g; hair Cr, 0.05 µg/g; and blood Pb, 1.3 µg/dL. Adjusted models revealed an inverted U-shaped association between hair Cu and VIQ, consistent with Cu as an essential nutrient that is neurotoxic in excess. At low levels of hair Cu (10th percentile, 5.4 µg/g), higher concentrations (90th percentiles) of the mixture of Mn, Pb, and Cr (0.3 µg/g, 2.6 µg/dL, and 0.1 µg/g, respectively) were associated with a 2.9 (95% CI: -5.2, -0.5)–point decrease in VIQ score, compared with median concentrations of the mixture. There was suggestive evidence of interaction between Mn and Cu. In secondary analyses, saliva Mn, hair Cu, and saliva Cr were selected as the biomarkers most strongly associated with VIQ score DISCUSSION: Higher adolescent levels of Mn, Pb, and Cr were associated with lower IQ scores, especially at low Cu levels. Findings also support further investigation into Cu as both beneficial and toxic for neurobehavioral outcomes. [ABSTRACT FROM AUTHOR]

Background Manganese (Mn) is an essential element required for growth and development, but higher body burdens have been associated with neurobehavioral decrements in children. Objectives We examined whether prenatal or postnatal Mn measured in deciduous teeth was associated with scores on a test of visuospatial learning and memory. Methods Deciduous teeth were collected from 142 participants (ages 10–14 years) residing near varied ferro‑manganese industry in Italy. Mn concentrations were measured in prenatal and postnatal tooth regions by laser ablation inductively coupled plasma mass spectrometry (ICP-MS). The Virtual Radial Arm Maze (VRAM), an animal-human analogue task, was used to assess visuospatial learning and memory. We used generalized additive, linear and zero-inflated Poisson mixed regression models to estimate associations between prenatal or postnatal Mn concentrations and repeated measures of all four VRAM outcomes: time, distance, working and reference memory errors. Effect measure modification by sex was examined in stratified models. Results U-shaped associations between prenatal Mn and VRAM outcomes were observed among girls only (p GAMM = 0.001 to 0.02 in stratified models). Compared to the mid-tertile of prenatal Mn, girls in the highest tertile took 7.7 s [95% CI: − 6.1, 21.5] longer to complete the task, traveled 2.3 maze units [0.1, 4.4] farther, and committed more working and reference memory errors (β for count ratio = 1.33 [1.01, 1.83]; 1.10 [0.98, 1.24], respectively). This association was not observed among boys. In contrast, for postnatal Mn, no significant associations were found, and patterns were similar for boys and girls. Conclusions The prenatal period may be a critical window for the impact of environmental Mn on visuospatial ability and executive function, especially for females. [ABSTRACT FROM AUTHOR]

Long-term exposure to environmental manganese (Mn) affects not only attention and neuromotor functions but also olfactory functions of a pre-adolescent local population who have spent their whole life span in contaminated areas. In order to investigate the effect of such exposure at the level of the central nervous system we set up a pilot fMRI experiment pointing at differences of brain activities between a non-exposed population (nine subjects) and an exposed one (three subjects). We also measured the volume of the olfactory bulb as well as the identification of standard olfactory stimuli. Our results suggest that young subjects exposed to Mn exhibit a reduction of BOLD signal, subjective odor sensitivity and olfactory bulb volume. Moreover a region of interest SPM analysis showed a specifically reduced response of the limbic system in relation to Mn exposure, suggesting an alteration of the brain network dealing with emotional responses. [ABSTRACT FROM AUTHOR]

Abstract: Results from a meta-analysis of aggregated data provoked a new analysis using individual data on the neuropsychological performance of occupationally exposed workers. Data from eight studies examining 579 exposed and 433 reference participants were included, 28 performance variables analyzed. The performance scores were adjusted for well-known individual-level covariates; the influence of possible, but unknown study-level covariates was attenuated by means of a z-normalization. Associations between performance and exposure were estimated by ANOVAs and ANCOVAs, the latter representing multi-level models. Four cognitive and motor performance variables each indicated significantly lower performances of exposed individuals when confounding was considered; slowed motor performances and deficits in attention and short-term memory were found. Performance on a single test was significantly related to the biomarker manganese in blood. The outcomes on susceptibility were weak. The slowing of responses was the most distinct feature of performances of exposed workers. It remains unclear, whether this result is related to the employed tests or provides important information about early stages of the neurotoxic impairment. More specific cognitive tests need to be employed to answer this question. The lack of dose–response relationships was related to features of the biomarker: it does not reflect the Mn in brain responsible for changes in performances. [Copyright &y& Elsevier]

Abstract: Introduction: A higher prevalence of individuals affected by Parkinsonism was found in Valcamonica, Italy. This may be related to ferro-alloy smelters in the area, releasing manganese (Mn) in the air, soil and water for about a century. There exists individual susceptibility for Mn neurotoxicity. Aim: To analyse how polymorphism in genes regulating Mn metabolism and toxicity can modify neurophysiological effects of Mn exposure. Materials and methods: Elderly (N =255) and adolescents (N =311) from Northern Italy were examined for neuromotor and olfactory functions. Exposure to Mn was assessed in blood and urine by atomic absorption spectroscopy and in soil by a portable instrument based on X-Ray fluorescence technology. Polymorphisms in the Parkinson-related gene ATPase type 13A2 (ATP13A2, also called PARK9: rs3738815, rs2076602, rs4920608, rs2871776 and rs2076600), and in the secretory pathway Ca2+/Mn2+ ATPase isoform 1 gene (SPCA1: rs218498, rs3773814 and rs2669858) were analysed by TaqMan probes. Results: For both adolescents and elderly, negative correlations between Mn in soil and motor coordination (R s =−0.20, p <0.001; R s =−0.13, p =0.05, respectively) were demonstrated. Also among adolescents, negative correlations were seen between Mn in soil with odor identification (R s =−0.17, p <0.01). No associations were seen for Mn in blood or urine. ATP13A2 polymorphisms rs4920608 and rs2871776 significantly modified the effects of Mn exposure on impaired motor coordination in elderly (p for interaction=0.029, p =0.041, respectively), also after adjustments for age and gender. The rs2871776 altered a binding site for transcription factor insulinoma-associated 1. Conclusions: ATP13A2 variation may be a risk marker for neurotoxic effects of Mn in humans. [Copyright &y& Elsevier]

Background: Metal exposure is a public health hazard due to neurocognitive effects starting in early life. Poor socio-economic status, adverse home and family environment can enhance the neurodevelopmental toxicity due to chemical exposure. Disadvantaged socio-economic conditions are generally higher in environmentally impacted areas although the combined effect of these two factors has not been sufficiently studied.Methods: The effect of co-exposure to neurotoxic metals including arsenic, cadmium, manganese, mercury, lead, selenium, and to socio-economic stressors was assessed in a group of 299 children aged 6-12 years, residing at incremental distance from industrial emissions in Taranto, Italy. Exposure was assessed with biological monitoring and the distance between the home address and the exposure point source. Children's cognitive functions were examined using the Wechsler Intelligence Scale for Children (WISC) and the Cambridge Neuropsychological Test Automated Battery (CANTAB). Linear mixed models were chosen to assess the association between metal exposure, socio-economic status and neurocognitive outcomes.Results: Urinary arsenic, cadmium and hair manganese resulted inversely related to the distance from the industrial emission source (β - 0.04; 95% CI -0.06, - 0.01; β - 0.02; 95% CI -0.05, - 0.001; β - 0.02 95% CI -0.05, - 0.003) while the WISC intellectual quotient and its sub-scores (except processing speed index) showed a positive association with distance. Blood lead and urinary cadmium were negatively associated with the IQ total score and all sub-scores, although not reaching the significance level. Hair manganese and blood lead was positively associated with the CANTAB between errors of spatial working memory (β 2.2; 95% CI 0.3, 3.9) and the reaction time of stop signal task (β 0.05; 95% CI 0.02, 0.1) respectively. All the other CANTAB neurocognitive tests did not show to be significantly influenced by metal exposure. The highest socio-economic status showed about five points intellectual quotient more than the lowest level on average (β 4.8; 95% CI 0.3, 9.6); the interaction term between blood lead and the socio-economic status showed a significant negative impact of lead on working memory at the lowest socio-economic status level (β - 4.0; 95% CI -6.9, - 1.1).Conclusions: Metal exposure and the distance from industrial emission was associated with negative cognitive impacts in these children. Lead exposure had neurocognitive effect even at very low levels of blood lead concentration when socio-economic status is low, and this should further address the importance and prioritize preventive and regulatory interventions. [ABSTRACT FROM AUTHOR]