Nigral iron deposition occurs across motor phenotypes of Parkinson's disease

Background and purpose: To investigate whether brain iron deposition correlates with motor phenotypic expressions of Parkinson's disease. Methods: We subtyped patients with Parkinson's disease according to their main motor symptoms (tremor, rigidity/bradykinesia) into three subgroups: tremor-dominant subgroup, akinetic/rigid-dominant subgroup, or mixed subgroup. The iron levels in bilateral substantia nigra, globus pallidus, putamen, the head of caudate, and red nucleus of 87 patients and 50 control subjects were assayed by measuring phase values using susceptibility-weighted phase imaging in a 3-tesla magnetic resonance system. The serum ceruloplasmin levels of all subjects were determined. Results: The bilateral average phase values of the substantia nigra and all other brain regions examined did not correlate with the main motor symptoms of Parkinson's disease in the total patient group or when patients were grouped according to serum ceruloplasmin levels. Significant correlations between serum ceruloplasmin levels and nigral bilateral average phase values were observed in the tremor and akinetic/rigid-dominant subgroups. Analysis of patients without prior dopaminergic medication exhibited similar results. Increased nigral iron content correlated with disease severity as assayed by the Unified Parkinson's Disease Rating Scale motor scores in the PD_AR subgroup. Conclusions: These findings suggest that nigral iron deposition, correlating with decreased serum ceruloplasmin levels, is a risk factor in Parkinson's disease across multiple motor phenotypic expressions.