The mean ages of the groups ranged from 45 to 55 years, but the difference was not statistically significant. The welders had a mean exposure of 30,968 hours. The average level of manganese in their blood was 20 mcg/L – twice the upper limit of normal.
At baseline, those with Parkinson’s disease had a significantly higher mean UPDRS3 score (19.7) than did either welders (8) or normal controls (1). The welders’ mean UPDRS3 score was significantly higher than was the normal controls’ score. But Dr. Criswell noted that welders were not significantly different from controls in terms of clinical parkinsonian symptoms.
Imaging revealed significantly higher pallidal index scores among welders than those of both control subjects and those with Parkinson’s disease. This difference was significantly related to increased exposure hours, but not to blood manganese levels.
After the researchers controlled for age, dopaminergic function also differed significantly between the groups. Welders had nearly 12% lower dopaminergic uptake in the anterior putamen, compared with the other two groups. The uptake pattern also varied significantly from those with Parkinson’s disease, measuring lowest in the caudate, followed by the anterior putamen and then the posterior putamen. "This pattern was reversed from the idiopathic Parkinson’s disease subject pattern," in which dopaminergic uptake was lowest in the posterior putamen, followed by the anterior putamen and finally, the caudate, Dr. Criswell said.
There were no significant interactions between dopaminergic uptake and pallidal index, manganese levels, and UPDRS3 scores. However, Dr. Criswell noted, the decrease in dopaminergic uptake among welders suggests presynaptic nigrostriatal dysfunction.
The findings suggest that manganese preferentially affects dopaminergic neurons in the caudate, rather than the putamen, Dr. W.R. Wayne Martin wrote in an accompanying editorial (Neurology 2011;76:1286-7). "In Parkinson’s disease, decreased caudate [dopaminergic uptake] correlates with impaired executive function," wrote Dr. Martin of the movement disorders clinic at Glenrose Rehabilitation Hospital in Edmonton, Alta. "This is consistent with the possibility that, with manganese toxicity, cognitive and behavioral symptomatology may be more prominent than motor changes, at least in its early stages."
However, he cautioned, only longitudinal follow-up can determine the true relationship between manganese exposure and any increased risk of Parkinson’s disease.
Ms. Lundin reported having no financial disclosures. Dr. Criswell reported receiving research support from numerous pharmaceutical companies; her study was funded by the Michael J. Fox Foundation for Parkinson’s Research, the National Institutes of Health, the American Parkinson Disease Association, Advanced Research Center at Washington University, the Greater St. Louis Chapter of the APDA, and the McDonnell Center for Higher Brain Function, and the Barnes-Jewish Hospital Foundation.
Dr. Martin reported receiving speaker honoraria from Allergan Inc.