Neurofunctional dopaminergic impairment in elderly after lifetime exposure to manganese

Abstract

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 24hour 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/m3 (median 18.42) in Valcamonica and 20.96 ng/m3 (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/m3 (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.

Effects of Ambient Air Pollution Exposure on Olfaction: A Review

“…A follow-up study in Italy by Lucchini et al (2014) examined odor discrimination ability among elderly subjects living in an area were ferroalloy plants were previously located. They found that both soil and airborne Mn were significant independent predictors of poorer olfaction, with a significant interaction between these two exposures.…”

“…They found that both soil and airborne Mn were significant independent predictors of poorer olfaction, with a significant interaction between these two exposures. These two studies in Italy are limited by their narrow geographic scope and in that the age groups examined were those particularly susceptible to toxic exposures, namely children and the elderly (Lucchini et al 2012, 2014). However, they do demonstrate a consistent trend of higher Mn exposure being related to poorer olfaction.…”

Cognitive Effects of Manganese in Children and Adults

“…Another study 75 investigated the relationship between environmental Mn contamination and neurological health outcomes in 250 elderly subjects (65-75 years old) residing in Valcamonica, an area in the province of Brescia, Italy, that was affected by ferromanganese plant emissions for about a century until 2001. The neuropsychological battery included the MiniMental State Examination (MMSE) for general cognitive assessment, the Story Recall Test to assess long-term verbal memory, the Raven's Colored Progressive Matrices (CPM) to measure clear-thinking ability, the Trail Making test to assess the ability for spatial planning in a visual-motor track, and the Digit Span (from WAIS) to evaluate short-term memory.…”

Impact of ferromanganese alloy plants on household dust manganese levels: Implications for childhood exposure

“…(Lucchini et al, 2007; Lucchini et al, 2012; Borgese et al, 2013; Lucchini et al, 2014) In addition, a higher prevalence of Parkinsonian disturbances in aged adults associated with environmental Mn exposure has also been reported. (Lucchini et al, 2007) Environmental Mn associated with airborne particulates and settled dust has been implicated as the exposure source/pathway to children and adults in these areas.…”