Parkinson’s Disease (PD) is characterized by loss of neuromelanin-containing dopaminergic neurons in the substantia nigra (SN), resulting in depigmentation as its pathological hallmark. Neuromelanin (NM)-sensitive-MRI consistently shows PD-related nigral signal-loss with limited evidence for longitudinal change. Nigral free-water (FW) derived from diffusion-MRI can track disease progression. This multimodal-serial study compared subregional annual depigmentation rates and FW in PD and controls. Longitudinal NM signal-loss and FW increase was seen in PD throughout the SN with significant acceleration compared to controls in the ventral-SN. There was no between-metrics correlation, suggesting that these promising serial biomarkers may track different aspects of PD progression.
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