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.