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

Exploration of the Reward System in Parkinson's Patients With Paradoxical Sleep Behavior Disorders: a Multimodal Imaging Study

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

Inclusion Criteria:

• Patients aged 45 to 80 years
• Patients diagnosed with idiopathic Parkinson's disease (PD) according to the Movement Disorder Society criteria
• Duration of Parkinson's disease progression ≥ 3 years
• Patients receiving chronic dopaminergic treatment including levodopa for at least one year to avoid tolerance issues during acute levodopa administration
• Ability to cooperate and understand, allowing strict compliance with the conditions set forth in the protocol
• Patients affiliated with or beneficiaries of a social security system
• Volunteer patients capable of providing informed consent to participate in the research

Exclusion Criteria:

• Patients suffering from neurological disorders other than idiopathic Parkinson's disease (PD)

• Patients with severe depression (Beck Depression Inventory \[20] (BDI) score > 30), apathy (Starkstein scale \[21] score ≥ 14), cognitive impairment (Montreal Cognitive Assessment \[MoCA] \[22] score < 25).

• Patients with impulse control disorders, defined by either of the following:

  • A score of ≥ 6 on the "Pathological Gambling" item, ≥ 8 on the "Compulsive Buying" item, ≥ 8 on the "Sexual Behavior" item, or ≥ 7 on the "Eating Behavior" item, and more than one positive response (score > 0) on the corresponding QUIP-RS items for Gambling, Compulsive Buying, Sexual Behavior, and Eating Behavior.
  • A total QUIP-RS score ≥ 10.

• Patients with severe motor symptoms: patients with an MDS-UPDRS III score > 45 will be excluded to avoid severe discomfort or interfering tremor (tremor item ≥ 3 in any body part) in the OFF state during PET-MRI acquisition. Patients with severe dyskinesias will also be excluded due to technical issues related to movement

• Patients under guardianship, curatorship, deprived of liberty, or under legal protection

• Pregnant or breastfeeding women

• Patients with contraindications to PET-MRI (e.g., those with pacemakers or insulin pumps, metallic prostheses or intracerebral clips, claustrophobia, neurosensorial stimulators or implantable defibrillators, cochlear implants, ferromagnetic ocular or cerebral foreign bodies near nervous structures, uncooperative or agitated patients, neurosurgical ventriculoperitoneal shunts, dental appliances)

• Refusal to participate