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
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
44
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
CHU Clermont-Ferrand, Clermont-Ferrand,
Clermont-Ferrand, France
CH Le Puy en Velay
Le Puy-en-Velay, France
[¹¹C]raclopride binding potential (BP, unitless) measured with PET-MRI in mesocorticolimbic brain structures between participants with and without RBD, off treatment.
The primary outcome measure corresponds to the Difference in binding potential (BP) of \[¹¹C\]raclopride in the brain structures of the mesocorticolimbic network between groups with and without RBD at baseline evaluation, off treatment, derived from PET-MRI imaging in mesocorticolimbic brain structures. The measurement tool is the \[¹¹C\]raclopride PET-MRI. BP is a unitless quantitative parameter (ratio between specifically bound radioligand and non-displaceable radioligand in tissue).
Time frame: During MRI exploration (3 months after inclusion visit)
[¹¹C]raclopride binding potential (BP, unitless) measured with PET-MRI in mesocorticolimbic brain structures between participants with and without RBD following acute administration of Levodopa
Time frame: During MRI exploration (3 months after inclusion visit)
MDS-UPDRS III motor score
UPPS impulsivity scale score
Time frame: at the inclusion visit
Starkstein apathy scale score
Time frame: at inclusion visit
BDI depression score
Time frame: at inclusion visit
Ardouin Scale of Behavior in Parkinson's Disease) scores (hypodopaminergic and hyperdopaminergic items)
Time frame: at inclusion visit
Total levodopa equivalent dose and for agonists (in mg/day)
Time frame: at inclusion visit
Voxel-wise parametric statistical maps (SPM) across the whole brain comparing PET parametric images ([¹¹C]raclopride BP)
Time frame: During MRI exploration (3 months after inclusion visit)
Voxel-wise parametric statistical maps (SPM) across the whole brain comparing MRI images.
Time frame: During MRI exploration (3 months after inclusion visit)
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