Spatiotemporal nigrostriatal iron accumulation in motor subtypes of Parkinson's disease: from early to late stage.

The spatiotemporal ordering of nigrostriatal iron deposition across different motor subtypes of Parkinson's disease (PD) remains poorly understand. This study explored the time course of nigrostriatal iron accumulation in 55 patients with postural instability and gait difficulty (PIGD) subtype and 53 patients with tremor-dominant (TD) subtype at early to late disease duration and 47 age-matched healthy controls (HC). Using quantitative susceptibility mapping, iron content was assessed in the substantia nigra (SN) and striatum. A spatial function method was employed to map the iron gradient along the principal axis of the subcortical structure. Nigrostriatal iron was compared among HC, PIGD/TD subgroup defined by disease duration [early, (<2 years); middle (2-6 years); late (>6 years)]. Associations with iron levels and motor symptoms were explored using partial correlation analysis. Nigrostriatal iron followed an inverted U-shaped progression, increasing initially and decreasing later in PIGD subtype. An S-shaped pattern was observed in TD subtype, increasing initially, decreasing later, then increasing again as disease progression. Iron distribution evolution of PD motor subtypes demonstrated opposite trends along medial-lateral axis (M-L) of the SN and anterior-posterior (A-P) axis of the putamen. Correlation analysis revealed that nigra iron content was positively associated with motor impairments, while caudate and putaminal iron level were negatively correlated with PIGD scores and Hoehn and Yahr scale in PIGD and TD subtype, respectively. These findings suggest that distinct nigrostriatal iron spatiotemporal pattern underlying different pathophysiology mechanism involved in these two PD motor subtypes. The opposite iron evolution trends along M-L axis of the SN and A-P axis of the putamen may provide a target for the development of new preventive or disease-modifying therapies.