Objective: To determine the clinical determinants and the role of serotonergic innervation on motor reserve in patients with de novo Parkinson’s disease.

Background: Patients with de novo Parkinson’s disease have profound nigro-striatal dopaminergic dysfunction, which does not always match the severity of motor symptoms at the patient-level. In particular, motor heterogeneity remains large at diagnosis, and patients with similar striatal dopaminergic depletion may have milder symptoms than expected, conceptualized as motor reserve. We decided to investigate the clinical and functional determinants of such discrepancy, using highly specific functional PET imaging to measure the degree of presynaptic striatal dopaminergic denervation and estimate motor reserve based on a residual model.

Method: We determined the expected motor severity given the individual presynaptic striatal dopaminergic dysfunction in a cohort of 26 patients with de novo Parkinson’s disease using highly-specific [11C]PE2I PET imaging for the dopamine transporter. Estimates for motor reserve were calculated as the difference of expected versus observed motor impairment. We used linear regression models to determine the clinical determinants of motor reserve, as well as the role of the serotonin transporter using [11C]DASB PET imaging.

Results: Motor reserve was not related to age, sex, and to the severity of non-motor symptoms in our cohort. However, we observed that extra-striatal serotonergic dysfunction was correlated to motor reserve. In particular, differences in serotonergic tonus determined by the serotonin transporter in the brainstem and limbic structures may modulate the role of nigro-striatal dopaminergic denervation on the severity of bradykinesia, rigidity and axial impairment in drug-naïve patients at diagnosis.

Conclusion: Cortical and subcortical serotonergic innervation may underly the variable expression of motor severity in patients with de novo Parkinson’s disease, highlighting the role of extra-striatal monoaminergic dysfunction for parkinsonian motor impairment.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/clinical-and-functional-determinants-of-motor-reserve-in-patients-with-de-novo-parkinsons-disease/