Quantified Striatal Dopaminergic Denervation as Predictor for Motor Outcomes in Parkinson's Disease

A hallmark of Parkinson's disease (PD) is progressive loss of dopamine terminals in the basal ganglia, with clinical symptoms including motor and non-motor manifestations such as bradykinesia, rigidity, and cognitive impairment. Dopamine transporter single-photon emission computed tomography (DaT-SPECT) can be used to assess dopaminergic denervation by detecting loss of striatal dopamine transporters (DaT).

We examined DaT binding scores' (DaTbs) association with motor outcomes in PD and explored its usefulness as a predictor of disease progression. Faster dopaminergic denervation in the basal ganglia was hypothesized to have stronger correlation and predictive value for poor motor outcomes.

Data was analyzed from the Parkinson's Progression Markers Initiative. DaTbs in the putamen and caudate nucleus were correlated with Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) scores for walking and balance difficulties, gait difficulties, and presence of dyskinesias. A predictive model using baseline speed of drop in DaT binding score was performed for each motor outcome.

All motor outcomes had mild, significantly negative correlation with DaTbs in the putamen and caudate nucleus, with similar degree of correlation per region. Speed of drop was predictive of only substantial gait difficulties when evaluated in the putamen but not the caudate.

These findings suggest that analyzing speed of drop in DaTbs, which occurs early in the motor phase of the disease, may be helpful for predicting clinical outcomes in PD. Longer observation of this cohort may provide further data to investigate DaTbs as a prognostic marker in PD.