In Vivo Noradrenergic System and Aging

Diving Into the in Vivo Noradrenergic System : Role of the alpha2C-adrenergic Receptors

The main goal of this research proposal is to provide, for the first time in humans, a wider understanding of the role of the noradrenergic system both in health and illness (here Parkinson's disease) through the use of a newly developed radiotracer visualizing alpha2C-ARs ([11C]ORM-13070) combined with a cutting-edge technology, the hybrid PET/MRI scanner. The secondary aim will be to determine whether the expected age- and PD-related changes in the noradrenergic system are paralleled by changes in neuropsychological performances (i.e. cognitive, motor and/or olfactory abilities).

Inclusion Criteria for the healthy controls:

• Age between 20 years and 80 years
• Weight between 40kg and 100kg
• Without neurologic or psychiatric history
• Without head trauma history including loss of consciousness superior to 30 minutes.
• With highly effective contraception for women of childbearing age
• Affiliated to a social security or similar scheme
• Not subject to any legal protection measures
• Participant must have signed an informed consent document

Inclusion Criteria for the patients with Parkinson's disease:

• Age between 40 years and 80 years
• Weight between 40kg and 100kg
• With an idiopathic Parkinson's disease (Dopa-sensitive)
• Without head trauma history including loss of consciousness superior to 30 minutes.
• Without associated neurological pathology
• With highly effective contraception for women of childbearing age
• Affiliated to a social security or similar scheme
• Not subject to any legal protection measures
• Participant must have signed an informed consent document

Exclusion Criteria for all participants :

• Subject receiving (or having received in the last month) somatic medication with cerebral or psychological effects (e.g., antihistamines), see list in Appendix1
• Subjects with a current or past dependence on alcohol or any other addictive substance according to DSM-IV-TR criteria, with the exception of nicotine and caffeine; -
• Subjects already participating in another biomedical research project or who have participated in a study using ionizing radiation within the past year;
• Pregnant woman parturient or breastfeeding
• MRI contraindications (: people using pacemaker or insulin pumps, with implanted or embedded metal objects in the head or body, claustrophobic, with neurosensory stimulators or implantable defibrillators, with cochlear implants, with ferromagnetic foreign bodies in the eye or brain close to nerve structures, agitation of the subject (uncooperative or agitated subjects), ventriculoperitoneal neurosurgical shunt valves, dental appliances)
• Subject with a contraindication to PET scans at the ORM: hypersensitivity to the active substance or to any of the excipients (sodium chloride)
• Subjects who are unable to understand or complete the study (language barrier, obvious lack of motivation, etc.) as judged by the investigator.
• Subjects who do not agree to be informed in the event of an incidental finding of an abnormality on MRI or during neuropsychological assessment.
• Persons deprived of their liberty by judicial or administrative decision.
• Persons receiving psychiatric care.
• Persons admitted to a health or social care facility for purposes other than research.