In a 5-year longitudinal study of 1,219 early PD patients, higher striatal DAT uptake on DAT-SPECT was associated with slower progression of autonomic dysfunction.

Supports striatal DAT availability as a prognostic biomarker for autonomic decline that can aid patient stratification and trial design, though it offers limited direct insight into therapeutic mechanisms or targets.

BACKGROUND: Striatal dopamine transporter (DAT) availability is a reliable marker of dopaminergic degeneration and has been shown to predict both motor worsening and cognitive decline in Parkinson's disease (PD). Although cross-sectional studies suggest that lower DAT is associated with autonomic dysfunction, its prognostic value for longitudinal autonomic progression remains unknown. METHODS: This study investigated the longitudinal association between striatal DAT availability and autonomic dysfunction in 1,219 individuals with PD. Single-photon emission computed tomography of DAT (DAT-SPECT) and Scales for Outcomes in Parkinson's Disease-Autonomic (SCOPA-AUT) scores were assessed at baseline and annually over a 5-year follow-up period. A linear mixed-effects model was employed to evaluate the interaction between DAT uptake (baseline or time-varying) and time. RESULTS: The mean baseline age and disease duration of the 1,219 participants were 63.0 years and 1.2 years, respectively. SCOPA-AUT scores increased by 0.8 points per year (P < 0.001). Linear mixed-effects models demonstrated that the interaction between baseline DAT availability and time was significant in the overall striatum (β = -0.54, P = 0.012), after adjustment for age, sex, baseline disease duration, DAT asymmetry index, MDS-UPDRS-III scores, and levodopa equivalent daily dose. The interaction between time-varying striatal DAT and time produced consistent results (β = -0.63, P = 0.018). CONCLUSION: Higher striatal DAT uptake was associated with slower progression of autonomic dysfunction, extending its established prognostic value beyond motor and cognitive decline.