Striatal dopaminergic depletion was associated with motor subtype conversion in Parkinson's disease

Abstract

Background

The instability of classical Parkinson's disease (PD) motor subtypes over the disease course suggests that motor subtype is influenced by disease severity. Tremor-dominant (TD) PD is susceptible to conversion to non-tremor-dominant (NTD) PD, with the risk increasing over time. This study investigates whether presynaptic striatal dopaminergic loss can predict the conversion from TD-PD to NTD-PD.

Methods

A total of 220 early TD-PD patients with baseline Dopamine Transporter Single-Photon Emission Computed Tomography (DAT-SPECT) data from the Parkinson's Progression Markers Initiative (PPMI) database were included. Patients were divided into high and low DAT uptake groups based on the median baseline striatal DAT uptake value. The Kaplan-Meier survival curve was used to compare the conversion rates of TD-PD subtype between the two groups. Multivariable Cox regression was used to further analyze the relationship between baseline striatal DAT uptake and TD-PD subtype conversion.

Results

The risk of conversion from TD to NTD was higher in the low striatal DAT group. In the multivariable Cox regression analysis, after adjusting for age, sex, baseline disease duration, MDS-UPDRS-II score and GDS score, the baseline striatal DAT uptake value was significantly associated with the conversion of TD-PD (HR = 0.39; 95 % CI 0.22–0.68; P = 0.001). In the stratified analysis, this association was not influenced by baseline TD or PIGD score.

Conclusions

In early-stage TD-PD, a high baseline presynaptic striatal dopaminergic reserve reduces the risk of future conversion to NTD-PD. This supports the notion that classical motor subtypes may reflect the disease stage or severity.