Poorer cognitive function and environmental airborne Mn exposure determined by biomonitoring and personal environmental monitors in a healthy adult population.

BACKGROUND/AIM: In the Santander Bay (Cantabria, northern Spain), a ferromanganese alloy plant is located. Our objective was to characterize the Mn personal exposure of adult healthy volunteers living in this highly Mn exposed region, and to determine its association with a poorer cognitive function. METHODS: Cross-sectional study analyzing 130 consecutive participants. Cognitive function was assessed by Stroop Color Word, Verbal Fluency tests, Trail Making Test (TMT), Digit Span (WAIS III) and Rey Osterrieth Complex Figure (ROCF) tests and crude scores were standardized according to NEURONORMA norms. Exposure to Mn was assessed in terms of source distance, by Personal Environmental Monitors (PEMs) allowing the separation of fine (PM2.5) and coarse (PM10-2.5) particles (obtaining the bioaccessible fraction by in-vitro bioaccessibility tests), and by biomarkers (blood, hair and fingernails). Age, sex, study level and number of years of residence were predefined as confounding variables and adjusted Mean Differences (MDs) were obtained. RESULTS: Statistically significant lower scores (negative MDs) in all test were observed when living near the industrial emission source, after adjusting for the predefined variables. Regarding PEMs results, statistically significant lower scores in all Stroop parts were obtained in participants with higher levels of Total Mn in All fractions (PM10). For Verbal Fluency tests, negative MDs were obtained for both bioaccessible fractions. Digit Span Backward scores were lower for those with higher levels in the bioaccessible coarse fraction, and negative MDs were also observed for the ROCF Delayed part and the non-bioaccessible fine fraction. As regards to Mn in fingernails, adjusted MDs of -1.60; 95%CI (-2.57 to -0.64) and -1.45; 95%CI (-2.29 to -0.61) for Digit Span Forward and Backward parts were observed. CONCLUSIONS: Our results support an association between poorer cognitive function and environmental airborne Mn exposure.

Biomonitoring and bioaccessibility of environmental airborne manganese in relation to motor function in a healthy adult population.

BACKGROUND/AIM: Santander, the capital of Cantabria, Spain (172,000 inhabitants) is 7 km from an industrial emission source (IES) of Mn located in a 10,000 inhabitants town (Maliaño) (annual air Mn arithmetic mean = 231.8 ng/m3; reference WHO guideline = 150 ng/m3). Our objective was to compare the motor function of adult healthy volunteers living in both places. METHODS: Cross-sectional study analyzing 130 consecutive participants. Exposure to Mn was assessed in terms of source distance from the IES, by Personal Environmental Monitors (PEMs) carried for 24 h by participants consisting of a portable impactor connected to a personal pump, and by biomarkers (blood, hair and fingernails). The impactor allowed the separation of fine (PM2.5) and coarse (PM10-2.5) particles and for each particle size in-vitro bioaccessibility tests with biologically active fluids were performed to separate the soluble (bioaccessible) from the insoluble (non-bioaccessible) fraction. Mean Differences (MDs) adjusted for age, sex, and study level, were obtained for motor function tests results. RESULTS: Regarding Grooved Pegboard, overall mean time to complete the test was 59.31 and 65.27 seconds (Standard Deviation = 10.11 and 11.69) for dominant and nondominant hands respectively. Statistically significant higher times (indicating worse function) were observed when living near the IES in both hands but MDs of only 1.22 and 2.05 seconds were obtained after adjusting for the predefined confounders (p = 0.373 and 0.221 respectively). Regarding Mn levels in their PEMs (in both bioaccessible and non-bioaccessible coarse&fine fractions) higher times were computed in participants with higher levels for the bioaccessible-fine fraction, with a MD that diminished but still yielded statistical significance after controlling for confounding: adjusted MD = 3.01 more seconds; 95%CI (0.44-5.38), p = 0.022. Poorer results were also observed for fingernails levels. Regarding Finger Tapping Test, no statistically significant differences were found with the exception of Mn fingernails levels. CONCLUSIONS: Our results suggest poorer motor function as assessed by Grooved Pegboard test in relation to "proximity to IES", "bioaccessible-fine fraction as determined by PEMs and "Mn fingernails levels". However, our findings were affected by confounding, and only the adjusted MD for the Mn bioaccessible-fine fraction remained of sufficient magnitude to maintain statistical significance.

Impact of Environmental Airborne Manganese Exposure on Cognitive and Motor Functions in Adults: A Systematic Review and Meta-Analysis.

BACKGROUND/OBJECTIVE: Whether environmental exposure to Manganese (Mn) in adults is associated with poorer results in cognitive and motor function is unclear. We aimed to determine these associations through a meta-analysis of published studies. METHODS: A systematic review was conducted to identify epidemiological studies on a population ≥18 years old exposed to environmental airborne Mn, and in which results on specific tests to evaluate cognitive or motor functions were reported. We consulted Medline through PubMed, Web of Science and SCOPUS databases. We also performed a manual search within the list of bibliographic references of the retrieved studies and systematic reviews. To weight Mn effects, a random effects versus fixed effect model was chosen after studying the heterogeneity of each outcome. RESULTS: Eighteen studies met the inclusion criteria. Among them, eleven studies reported data susceptible for meta-analysis through a pooled correlation or a standardized means difference (SMD) approach between exposed and non-exposed groups. Regarding cognitive function, the results of the studies showed heterogeneity among them (I2 = 76.49%, p < 0.001). The overall effect was a statistically significant negative correlation in the random effects model (pooled r = -0.165; 95%CI: -0.214 to -0.116; p < 0.001). For SMD, the results showed a lower heterogeneity with a negative SMD that did not reach statistical significance under the fixed effects model (SMD = -0.052; 95%CI -0.108 to 0.004; p = 0.068). Regarding motor function, heterogeneity (I2 = 75%) was also observed in the correlation approach with a pooled r (random effect model) = -0.150; 95%CI: -0.219 to -0.079; p < 0.001. Moderate heterogeneity was observed according to the SMD approach (I2 = 52.28%), with a pooled SMD = -0.136; 95%CI: -0.188 to-0.084; p < 0.001, indicating worse motor function in those exposed. CONCLUSIONS: Correlation approach results support a negative effect on cognitive and motor functions (the higher the Mn levels, the poorer the scores). Regarding the SMD approach, results also support a worse cognitive and motor functions in those exposed, although only for motor function statistical significance was obtained.

A Review on the Environmental Exposure to Airborne Manganese, Biomonitoring, and Neurological/Neuropsychological Outcomes.

The occupational exposure to airborne manganese (Mn) has been linked for decades with neurological effects. With respect to its environmental exposure, the first reviews on this matter stated that the risk posed to human health by this kind of exposure was still unknown. Later, many studies have been developed to analyze the association between environmental Mn exposure and health effects, most of them including the measure of Mn in selected human biomarkers. This review aims at collecting and organizing the literature dealing with the environmental airborne Mn exposure (other routes of exposure were intentionally removed from this review), the biomonitoring of this metal in different body matrices (e.g., blood, urine, nails, hair), and the association between exposure and several adverse health effects, such as, e.g., neurocognitive, neurodevelopmental, or neurobehavioral outcomes. From the different exposure routes, inhalation was the only one considered in this review, to take into account the areas influenced by industrial activities closely related to the Mn industry (ferromanganese and silicomanganese plants, Mn ore mines, and their processing plants) and by traffic in countries where a fuel additive, methylcyclopentadienyl manganese tricarbonyl (MMT), has been used for years. In these areas, high air Mn levels have been reported in comparison with the annual Reference Concentration (RfC) given by the US EPA for Mn, 50 ng/m3. This review was performed using Scopus and MEDLINE databases with a keyword search strategy that took into account that each valid reference should include at least participants that were exposed to environmental airborne Mn and that were subjected to analysis of Mn in biomarkers or subjected to neurological/neuropsychological tests or both. Overall, 47 references matching these criteria were included in the discussion. Most of them report the measure of Mn in selected biomarkers (N = 43) and the assessment of different neurological outcomes (N = 31). A negative association is usually obtained between Mn levels in hair and some neurological outcomes, such as cognitive, motor, olfactory, and emotional functions, but not always significant. However, other biomarkers, such as blood and urine, do not seem to reflect the chronic environmental exposure to low/moderate levels of airborne Mn. Further studies combining the determination of the Mn exposure through environmental airborne sources and biomarkers of exposure and the evaluation of at least cognitive and motor functions are needed to better understand the effects of chronic non-occupational exposure to airborne Mn.