Spatiotemporal Progression Patterns of Striatal Dopamine Depletion and Cerebral Hypoperfusion in Parkinson's Disease

The identification of Parkinson's disease (PD) subtypes is crucial for predicting the disease course and designing personalized therapeutic strategies.

The aim of the study was to characterize the heterogeneity of the spatiotemporal evolutionary patterns of striatal dopamine depletion and cerebral hypoperfusion in PD.

We retrospectively enrolled 708 patients with newly diagnosed PD and 50 healthy controls who underwent dual-phase ¹⁸F-FP-CIT PET scans. We applied subtype and stage inference (SuStaIn) to delineate three PD subtypes after quantifying the dual-phase ¹⁸F-FP-CIT PET data. We compared the baseline clinical features as well as the longitudinal motor and cognitive outcomes between subtypes.

Subtype 1 (n = 406) initially presented with asymmetric dopamine loss in the posterior putamen, followed by dopaminergic deficits in other striatal subregions and, later, cerebral hypoperfusion. Subtype 2 (n = 205) exhibited diffuse and symmetric striatal dopamine loss in the early stages, followed by cerebral hypoperfusion in the mid-stages. Subtype 3 (n = 89) initially showed the parieto-occipital hypoperfusion, followed by cerebral hypoperfusion in other cortical areas and striatal dopamine depletion. Subtype 2 had an older age of onset, and subtype 3 had a younger age of onset and a lower prevalence of rapid eye movement sleep behavior disorder. Time-dependent Cox regression models showed that the risk of dementia conversion within a follow-up period of 4 years was higher in subtypes 2 and 3 (hazard ratios 1.772 and 2.802, respectively) than subtype 1, after the confounding effects were adjusted. The risk of developing levodopa-induced dyskinesia and freezing of gait was comparable between subtypes.

The spatiotemporal trajectories of striatal dopamine depletion and cerebral hypoperfusion on dual-phase ¹⁸F-FP-CIT PET images could serve as a potential progression marker for cognitive decline in early-stage PD. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.