Dentate nucleus iron deposition is a potential biomarker for tremor‐dominant Parkinson's disease

Parkinson's disease (PD) is a heterogeneous neurodegenerative disorder with variable clinicopathologic phenotypes and underlying neuropathologic mechanisms. Each clinical phenotype has a unique set of motor symptoms. Tremor is the most frequent initial motor symptom of PD and is the most difficult symptom to treat. The dentate nucleus (DN) is a deep iron‐rich nucleus in the cerebellum and may be involved in PD tremor. In this study, we test the hypothesis that DN iron may be elevated in tremor‐dominant PD patients using quantitative susceptibility mapping. Forty‐three patients with PD [19 tremor dominant (TD)/24 akinetic rigidity (AR) dominant] and 48 healthy gender‐ and age‐matched controls were recruited. Multi‐echo gradient echo data were collected for each subject on a 3.0‐T MR system. Inter‐group susceptibility differences in the bilateral DN were investigated and correlations of clinical features with susceptibility were also examined. In contrast with the AR‐dominant group, the TD group was found to have increased susceptibility in the bilateral DN when compared with healthy controls. In addition, susceptibility was positively correlated with tremor score in drug‐naive PD patients. These findings indicate that iron load within the DN may make an important contribution to motor phenotypes in PD. Moreover, our results suggest that TD and AR‐dominant phenotypes of PD can be differentiated on the basis of the susceptibility of the DN, at least at the group level. Copyright © 2016 John Wiley & Sons, Ltd. The tremor‐dominant (TD) Parkinson's disease group showed increased susceptibility in the bilateral dentate nucleus (DN) compared with the healthy control group. No difference was seen in R2* between the TD group and healthy control group, indicating that the deposited iron in DN may comprise smaller iron particles. The DN susceptibility in drug‐naive PD patients was positively correlated with tremor score. These findings indicate that iron load within DN may make an important contribution to motor phenotypes in PD.