Presynaptic Dopaminergic function and brain metabolism in the Nigrostriatal and Mesocortical Systems in Early onset-Parkinson’s Disease

Introduction: To investigate presynaptic dopaminergic functions and brain metabolism in vivo in both nigrostriatal and mesocortical pathways in patients with Early-onset Parkinson’s disease (EOPD) with and without mutations.

Methods: We included 33 unrelated EOPD patients: 19 genetic mutation-carriers and 14 non-carriers. The two groups of dopamine transporter imaging (¹¹C-CFT) were compared at voxel-wise and region of interests (ROI). The brain metabolism images (¹⁸F-FDG) were compared at voxel-wise. Motor and nonmotor symptoms were assessed with specific scales and questionnaires.

Results: There was no significant difference in age and gender between the two groups. The voxel-wise and ROI analysis of DAT showed that the impair of dopamine pathway in prefrontal，midbrain cortex was more extensive in patients with EOPD with genetic mutation compared to non-carriers, but similar in the bilateral striatum. Genetic mutation carriers had hypometabolism decreased cortical activity in orbitofrontal cortex regions.

Conclusions: The findings indicate that the occurrence and development of EOPD with and without mutations may involve different dopamine pathway damage, and genetically defined specific subtypes may have implication for deliver personalized precision treatment.