Executive functions in school-aged children exposed to airborne manganese: A multilevel analysis.

Neuropsychological alterations have been identified in populations heavily exposed to metals with neurotoxic potential, such as manganese (Mn). This study examined the associations between Mn environmental exposure in school-aged children and executive functions, using structural equation modeling. Children, aged between 7 and 12 years (N = 181), were recruited from four elementary schools located in a region that is under the influence of atmospheric emissions from a ferro-manganese alloy plant in the municipality of Simões Filho, Bahia, Brazil. The following cognitive functions were evaluated: Intelligence, Inhibitory Control, Cognitive Flexibility, Verbal and Design Fluency, Verbal and Visual Working Memory and Attention. We performed structural equation modeling to identify the following executive functions latent variables: working memory, inhibitory control and cognitive flexibility. We further analyzed the relations between executive functions and Mn measured in hair (MnH) and toenails (MnTn) with linear mixed models, after controlling for co-variables. A positive effect at the individual level on working memory, inhibition control and cognitive flexibility was observed with MnTn after controlling for co-variables, but no association was found with MnH levels. However, children attending school most environmentally exposed to Mn emissions, which had the highest rate of Mn dust deposition, had the poorest scores on working memory. These findings suggest both benefits and risk of Mn on children's cognitive development.

Delta-Aminolevulinic Acid Dehydratase, Low Blood Lead Levels, Social Factors, and Intellectual Function in an Afro-Brazilian Children Community.

Delta-aminolevulinic acid dehydratase (ALAD) enzyme catalyzes the second phase of the heme biosynthesis and is involved in lead toxicokinetics. This research aimed to evaluate its influence on the relationship between blood lead (PbB) levels and intellectual performance in Afro-Brazilian children. PbB, hemoglobin concentration, ALAD activity, and polymorphism were determined in whole blood. Anthropometric, socioeconomic, and family environment stimuli data were collected with appropriate instruments. The non-verbal intelligence of children and their mothers or guardians was assessed using the correspondent Raven's Progressive Matrix versions. The medians (range) of PbB levels and ALAD activity were 1.0 µg/dL (0.1-21.3) and, 71 U/L (31-113), respectively. ALAD G177C was distributed as follows: 97.9% for ALAD1/1 and 2.1% for ALAD1/2 genotypes. The mean of Raven raw score was 19.3 (± 5.6) points and there were no differences according to sex or environmental Pb exposure. No statistically significant association was observed between PbB level and children's IQ. However, ALAD activity presented an inverse significant association with PbB levels, children's percentile IQ, and children's IQ/Age ratio, suggesting a neuroprotective role of ALAD1 genotype in those with low PbB level.

Interaction of Toxoplasma gondii infection and elevated blood lead levels on children's neurobehavior.

A chronic infection caused by Toxoplasma gondii was considered asymptomatic in immunologically healthy humans, but results from animal and epidemiological studies led to a reconsideration of this assumption. The objective of this study was to evaluate the seroprevalence of T. gondii infection and its possible effects on the behavior of school-aged children in Bahia, Brazil. Serum anti-body determinations were performed by Enzyme-linked Immunosorbent Assay (ELISA). Blood lead levels (BLL) were measured by graphite furnace atomic absorption spectrometry (GFAAS). The evaluation of a child's behavior was assessed using the Child Behavior Check List (CBCL). Multivariate models applying logistic regression were used to test the association of chronic T. gondii infection and BLL with behavioral outcomes in children. Seroprevalence for anti-T. gondii IgG antibody was 43.7 % (95 %-CI: 35.8-51.9). Significant associations between chronic T. gondii infection and total behavioral problems (OR = 2.50; 95 %-CI: 1.06-5.88), internalizing spectrum problems (OR = 4.35; 95 %-CI: 1.11-17.14) and rule breaking (OR = 2.61; 95 %-CI: 1.12-6.05) were observed. A possible interaction between toxoplasmosis prevalence and lead exposure was detected. Children with above the median BLL and positive for IgG anti-T. gondii showed a 5.51-fold increase (95 %-CI: 1.75-17.38) in the chance of displaying disobedient behavior. The results suggest that T. gondii infection may be contributing to the high indices of behavioral changes. Moreover, these findings are the first evidence for a possible interaction between chronic T. gondii infection and elevated blood lead levels on children's neurobehavior.

Environmental Co-Exposure to Lead and Manganese and Intellectual Deficit in School-Aged Children.

Studies have demonstrated that, for urban children, dust represents the main exposure to sources of metals like lead (Pb) and manganese (Mn). We aimed to investigate the exposure to these metals and their association with intellectual deficit in children living in an industrial region. This cross-sectional study recruited volunteers from four elementary schools in the town of Simões Filho, Brazil. We evaluated 225 school-aged children (7⁻12 years) for blood lead (PbB) and manganese hair (MnH) and toenails (MnTn) by graphite furnace atomic absorption spectrometry. Child and maternal IQs were estimated using the Wechsler Abbreviated Scale for Intelligence (WASI). Median and range PbB were 1.2 (0.3⁻15.6) µg/dL. MnH and MnTn medians (ranges) were 0.74 (0.16⁻8.79) µg/g and 0.85 (0.15⁻13.30) µg/g, respectively. After adjusting for maternal IQ, age and Mn exposure, child IQ drops by 8.6 points for a 10-fold increase in PbB levels. Moreover, an effect modification of Mn co-exposure was observed. In children with low MnTn, association between Pb and child IQ was not significant (ß = -6.780, p = 0.172). However, in those with high MnTn, the association was increased by 27.9% (ß = -8.70, p = 0.036). Low Pb exposure is associated with intellectual deficit in children, especially in those with high MnTn.

Airborne manganese exposure and neurobehavior in school-aged children living near a ferro-manganese alloy plant.

Excessive exposure to Mn can lead to its accumulation in the brain with neurotoxic consequences. In children, elevated Mn has been associated with deficits in certain neuropsychological domains such as cognition, motor function, memory and attention, and in some instances, hyperactivity and behavioral problems. The aim of this study was to evaluate behavioral effects in school-aged children living near a ferro-manganese alloy plant and examine their association with Mn exposure. Occipital hair, toenails and blood samples were collected from 225 children (7-12 years old) enrolled in four elementary schools with different levels of exposure to Mn, based on dust Mn deposition rates. Full data set collection was completed and run from 165 children. Mn in hair (MnH), toenails (MnTn), blood (MnB) and blood lead levels (PbB) were determined by graphite furnace atomic absorption spectrometry. Children's behavior was assessed with the Child Behavior Check List (CBCL) reported by parents. Median levels and range of MnH, MnT and MnB were, respectively, 0.73 µg/g (0.16-8.79), 0.84 µg/g (0.15-9.29) and 8.98 µg/L (1.51-40.43). Median and range of PbB were 1.2 µg/dL (0.2-15.6). MnH and MnB were not associated with any scale of the CBCL behavior scores. We found a positive association between logMnTn and raw total CBCL score (ß = 10.17, p = 0.034), adjusting for sex, age, maternal IQ and logPbB. Analyses using Generalized Additive Model showed non-linear associations between MnTn and externalizing behavior (p = 0.035), as well as with the related subscales: aggressive behavior (p = 0.045) and rule-breaking behavior (p = 0.024). Further positive associations were observed between MnTn and thought problems (p = 0.031) and social problems (p = 0.027). These findings corroborate previous studies showing an association between Mn exposures and externalizing behavior. Our results suggest that toenail Mn, as a biomarker of environmental exposure, is associated with disruptive behavior in children living near a ferro-manganese alloy plant.

Noninvasive biomarkers of manganese exposure and neuropsychological effects in environmentally exposed adults in Brazil.

Manganese (Mn), an essential element to humans, in excess can cause neurotoxic damage. So far, Mn exposure assessment has no ideal biomarker. This study aims to investigate the association between Mn exposure, using noninvasive biomarkers, and neuropsychological effects in environmentally exposed adults. The residents of two communities near to a ferromanganese refinery in Bahia, Brazil were evaluated. Volunteers aged 15-55 of both sexes provided scalp hair, axillary hair, fingernail and saliva specimens for Mn determination by electrothermal absorption spectrometry. Several neuropsychological tests were used to evaluate cognitive, attention, memory, motor and executive functions. Significant correlations were observed between Mn in hair (MnH, median 8.95 µg/g), axillary hair (MnAxH,18.49 µg/g) and fingernail (MnFN, 6.91 µg/g) with the performances in several neuropsychological tests. No association was observed between manganese levels in saliva (MnSal, 4.2 µg/L) and any neuropsychological function. Multiple regression analysis detected an inverse association between Log MnH and IQ (ß=-4.76 [CI 95% -9.17 to -0.36]) and between Log MnFN and visual working memory (ß=-3.33 [CI 95% -6.15 to -0.52]). Direct association was observed between Log MnFN and time of completion in the cognitive flexibility task (ß=56.29 [CI 95% 2.41-110.18]). The Mn biomonitoring using noninvasive biomarkers was able to detect high exposure levels, which were associated with detrimental neuropsychological effects in adults exposed to industrial emissions.

Elevated airborne manganese and low executive function in school-aged children in Brazil.

Exposure to airborne manganese (Mn) has been associated with neurotoxic effects, including motor and cognitive deficits. The main deficits related to excessive exposure to Mn are predominantly the dysfunction of fronto-striatal and dopaminergic circuits observed in animal experimental studies, which are involved in attention, working memory and motor function. The present study aims to assess the association between elevated Mn exposure and performance on executive function and attention neuropsychological tests in children living in two communities near a ferro-manganese alloy plant. Seventy children aged between 7 and 12 years with no history of neurologic disease and an estimated IQ >68 (Vocabulary and Block Design subtests) that had lived near the iron-Mn production alloy plant for at least 1.5 years were included. Participants were assessed for cognitive functioning with neuropsychological measures for sustained attention (Test of Visual Attention - TAVIS-3R), cognitive flexibility (WCST), and verbal and visual working memory (WISC-III Digit Span subtest and Corsi Block). Manganese hair (MnH) levels were used as a biomarker of exposure. Mean scores among study participants were lower than general population norms/averages for block design, digit span, reaction time and commission errors. The median MnH level was 11.48 (range 0.52-55.74) µg/g, and no difference between sexes was observed. Spearman's correlation analysis showed a significant inverse correlation between MnH levels and estimated IQ (rho=-0.448, p=0.0001), Vocabulary (rho=-0.272, p=0.02), Block Design (rho=-0.485, p=0.00002) and Digit Span (rho=-0.410, p=0.0004). Multiple regression analyses detected inverse associations between log MnH and scores on estimated IQ (ß=-9.67; 95%CI=-16.97 to -2.37), Block Design (ß=-2.50; 95%CI=-3.91 to -1.10) and Digit Span Total (ß=-2.59; 95%CI=-4.13 to -1.05) standardized scores and the number of correct answers in forward and backward Digit Span methods, after adjusting for covariates (ß=-1.32=95%CI=-2.23 to -0.40; ß=-1.09 95%CI=-2.02 to -0.16, respectively). The results suggest that airborne Mn exposure may be associated with lower IQ and neuropsychological performance in tests of executive function of inhibition responses, strategic visual formation and verbal working memory. Executive function is dependent on the fronto-striatal circuit, which may be disrupted by Mn accumulation in the brain.