Association of Striatal Dopaminergic Depletion and Cerebral Perfusion With Cognition in Brain-First and Body-First Parkinson's Disease.

Purpose: We aimed to investigate whether the patterns of striatal subregional dopamine loss and cerebral perfusion alterations differed between the 2 types of Parkinson's disease (PD) (ie, brain-first and body-first PD) and had an impact on cognitive prognosis in PD.

Patients and methods: This retrospective study reviewed the data of newly diagnosed patients with PD who underwent dual-phase dopamine transporter (DAT) scans in tertiary medical centers. We classified the patients into 2 groups based on the rapid eye movement sleep behavior disorder (RBD) screening questionnaire: PD with RBD (body-first PD) and PD without RBD (brain-first PD) groups. Then, we investigated intergroup differences in subregional DAT availability, regional cerebral perfusion, and the rates of dementia conversion.

Results: After adjusting for confounding variables, the body-first group exhibited lower DAT availability in the anterior putamen than the brain-first group (β=-0.10, SE=0.04, P =0.044). In comparative analyses of regional cerebral perfusion, the body-first group exhibited lower regional perfusion in the bilateral parieto-occipital area and left cerebellum than the brain-first group, and vice versa in the brainstem, left hippocampus, right pallidum, bilateral thalamus, and ventral diencephalon. The dementia conversion rate was significantly higher in the body-first group (HR=1.78, P =0.027) than in the brain-first group, which was largely mediated by DAT availability in the anterior putamen and parieto-occipital cerebral perfusion in mediation analyses.

Conclusions: This study demonstrated that the patterns of striatal subregional dopamine depletion and regional cerebral perfusion differed between the brain-first and body-first PD subtypes, and these differences largely mediated inter-subtype differences in cognitive outcome.