PET-MRI of Reward System in Parkinson's Disease With RBD

Summary

Impulse control disorders (ICDs) are frequently observed in Parkinson's disease (PD) and can have a major functional impact on the quality of life of both the patient and their entourage. The primary risk factor for the emergence of ICDs in PD is long-term dopaminergic treatment, but other risk factors, such as rapid eye movement sleep behavior disorder (RBD), have recently been identified. The mechanisms leading to ICDs in PD remain debated, but it has been shown that the dopaminergic mesocorticolimbic pathways play a key role in reward, learning, and reinforcement processes, as well as in the regulation of impulsivity. PET studies using \[11C\]raclopride, a tracer that allows evaluation of the postsynaptic availability of dopamine D2/D3 receptors, have demonstrated abnormal sensitization of the mesocorticolimbic dopaminergic system (the reward system), particularly in the ventral striatum, in Parkinson's patients with ICDs when presented with appetitive stimuli or during gambling tasks. However, this has never been studied in patients with and without RBD. Parkinson's patients with RBD may present greater impairment of mesocorticolimbic pathways than those without RBD, particularly abnormal sensitization and postsynaptic modifications of the dopaminergic system, which could predispose patients to the emergence of ICDs when exposed to dopaminergic agonists. Confirming a particular pattern of denervation in Parkinson's patients with RBD that may favor the emergence of ICDs constitutes a personalized medicine approach with a readily identifiable risk marker in routine clinical practice and offers the possibility of adapting the management of these patients.

The main objective of this study is to investigate the availability of D2 dopaminergic receptors in subcortical structures (particularly the mesocorticolimbic system) in patients with idiopathic Parkinson's disease, depending on the presence or absence of RBD

Conditions

• Parkinson's Disease (PD)

Interventions

OTHER

PET-MRI (Positron Emission Tomography - Magnetic Resonance Imaging).

The PET-MRI will be performed using a Siemens Biograph mMR hybrid PET-MRI scanner. A 60-minute dynamic PET acquisition will begin following the intravenous injection of \\\[¹¹C\]raclopride (a radiotracer agonist of dopamine D2/D3 receptors) synthesized in the radiopharmaceutical laboratories of CERMEP. Simultaneously with the PET acquisition, brain MRI sequences will be acquired: 3D anatomical T1 and 3D T2, SWI, diffusion MRI (DTI), resting-state functional MRI, and arterial spin labeling (ASL) perfusion MRI. Patients will undergo two PET-MRI scans on two consecutive days under two pharmacological conditions: Off and On dopamine: * Day 1:\*\* The first PET-MRI session (TEPDopaOff) will be performed after a 12-hour withdrawal from usual dopaminergic treatment (Off dopamine). * Day 2:\*\* The second PET-MRI session (TEPDopaOn) will be similar to the first, except it will take place 1 hour after administration of immediate-release Levodopa

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand

  lead OTHER

Principal Investigators

• Charlotte BEAL · University Hospital, Clermont-Ferrand

Study Design

Allocation

NON_RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

45 Years

Max Age

80 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-01-01

Primary Completion

2028-01-01

Completion

2029-01-01

Countries

• France

Study Locations