OBJECTIVE: The motor severity in Parkinson's disease (PD) is believed to parallel with dopaminergic terminal degeneration in the striatum although the terminal was reported to be virtually absent by 4 years post-diagnosis. Meanwhile, neuromelanin-laden dopamine neuron loss in the substantia nigra (SN) elucidated a variability at early stages and gradual loss with less variability 10 years post-diagnosis. Here, we aimed to clarify the correlation between motor impairments and striatal dopaminergic terminal degeneration and nigral neuromelanin-laden dopamine neuron loss at early to advanced stages of PD. METHODS: Ninety-three PD patients were divided into early and advanced subgroups based on motor symptom duration and whether motor fluctuation was present. Striatal dopaminergic terminal degeneration was evaluated using a presynaptic dopamine transporter tracer, 123 I-ioflupane SPECT. Nigral neuromelanin-laden dopamine neuron density was assessed by neuromelanin-sensitive MRI (NM-MRI). RESULTS: In patients with early-stage (motor symptoms for ≤8 or 10 years), motor dysfunction during the drug-off state was paralleled by a decline in 123 I-ioflupane uptake in the striatum despite the absence of a correlation with reductions in NM-MRI signals in SN. Meanwhile, in patients with advanced-stage (motor symptoms for >8 or 10 years and with fluctuation), the degree of motor deficits during the drug-off state was not correlated with 123 I-ioflupane uptake in the striatum, despite its significant negative correlation with NM-MRI signals in SN. INTERPRETATION: We propose striatal dopaminergic terminal loss measured using 123 I-ioflupane SPECT and nigral dopamine neuron loss assessed with NM-MRI as early-stage and advanced-stage motor impairments biomarkers, respectively. This article is protected by copyright. All rights reserved.