The neurobehavioral impact of manganese: results and challenges obtained by a meta-analysis of individual participant data.

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.