Association between brain iron deposition and pure apathy in Parkinson's disease: a cross-sectional quantitative susceptibility mapping imaging study.

Background: Apathy, a decline in goal-directed motivated behavior, is a common non-motor symptom (NMS) in Parkinson's disease (PD). Previous studies have suggested that PD patients with apathy exhibit increased iron levels in the cerebrospinal fluid (CSF) and the iron levels are positively correlated with the severity of apathy, indicating that apathy in PD may be related with brain iron accumulation. Specifically, quantitative susceptibility mapping (QSM), an emerging brain magnetic resonance imaging (MRI) technique, can be used to sensitively detect the iron deposition in the brain Methods: A total of 29 patients with PD-PA, 33 PD without pure apathy (PD-NPA), and 32 healthy controls (HCs) were collected. All participants underwent three-dimensional T1-weighted imaging (3DT1) and QSM scans. The susceptibility values of PD-PA, PD-NPA, and HC groups were compared at whole brain voxel-wise level and the region of interest (ROI)-wise level, respectively. Moreover, correlation analysis between apathy symptoms and brain iron deposition was further performed in the PD-PA group. Results: Relative to the HCs, patients with PD demonstrated increased susceptibility values (consistent with higher brain tissue iron deposits) in substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) of the midbrain [P Conclusions: In patients with PD-PA, brain regions associated with brain iron deposition were mainly located in the "mesocorticolimbic loop" (SFGmed and ACC), as well as the STG and thalamus. The present study suggested that abnormal iron deposition in these core brain regions may be associated with abnormal top-down and bottom-up neuroregulation and involved in the mechanism of PD apathy. The present study provides new insights into the pathophysiologic mechanism of PD-PA.