Identifying brain degeneration patterns in early-stage Parkinson’s disease: a multimodal MRI study

Parkinson’s disease (PD) is a highly heterogeneous neurodegenerative disorder. This study aimed to identify different patterns of early brain degeneration in PD patients and investigate their clinical relevance. 179 early-stage PD patients and 115 healthy controls were included. We assessed cortical morphology, white matter microstructure, and subcortical iron metabolism using multimodal magnetic resonance imaging and employed clustering techniques to identify subtypes. Two subtypes were identified: the early-deterioration subtype, characterized by fronto-temporal atrophy, parietal thickening, widespread reductions in fractional anisotropy (FA) values, and increased subcortical iron content, which exhibited more severe baseline symptoms and a trend of faster memory decline; and the early-compensatory subtype, characterized by rostral middle frontal atrophy, parietal-occipital thickening, increased FA values, and normal iron content, which exhibited milder symptoms initially but experienced faster progression of both motor and non-motor symptoms. These discoveries provided new insights into disease heterogeneity and facilitated the exploration of early neurodegenerative mechanisms.