Deciphering the Mechanisms of Central BP Regulation in Patients With PD Associated With Orthostatic Hypotension

Phase 1 objective: test the feasibility of using a 3Tesla MRI scanner instead of a 7Tesla MRI scanner to measure brainstem responses to LBNP in healthy participants using BOLD fMRI

Phase 2 primary objective: compare the brainstem responses to LBNP in patients with PD associated with OH to PD patients without OH using BOLD fMRI

Phase 2 secondary objectives:

• assess modulation of functional connectivity in response to LBNP (effective connectivity analysis by psycho-physiological interactions (PPI)) and determine differences between the two groups
• assess functional connectivity in resting state and determine differences between the two groups
• compare structural connectivity in both groups using tractography
• compare renal response to LBNP in both groups using contrast-enhanced ultrasound
• compare pre-cerebral flow response to LBNP in both groups

Phase 1:

Inclusion criteria

• Signed informed consent
• Age ≥ 18 years and <75 years
• Normal office blood pressure (<140/90 mmHg)
• For women of childbearing potential: using or willing to use during the study a reliable contraception method compatible with MRI

Exclusion criteria

• Schellong test showing OH (drop of Systolic BP >20 mmHg or Diastolic BP >10 mmHg)
• Pregnant or lactating women
• Refusal to be informed of incidental findings
• Any medication (acute or chronic prescription) except oral contraception
• Clinical significant abnormal blood test as assessed by the investigator
• Chronic or acute illness
• Concomitant participation in a clinical trial
• Blood donation in the 60 previous days
• Contra-indications for MRI
• Unable to follow study procedures
• Having a hierarchical relationship with the investigator or being family of the investigator

Phase 2:

Inclusion criteria

• Signed informed consent
• Fulfilling Movement Disorder Society clinical criteria for "clinically established PD"
• Age ≥18 years and <75 years
• PD treated by dopamine replacement therapy (DRT)
• Willing and able to comply with the visit schedule and study procedures
• Autonomous in daily life
• Schellong test showing OH (drop of Systolic BP >20 mmHg or Diastolic BP >10 mmHg)(for study group with OH) or no OH (for studygroup without OH)
• For women of childbearing potential: using or willing to use during the study a reliable contraception method compatible with MRI

Exclusion criteria

• Unable to give an informed consent
• BP > 180/110 mmHg on 24-hour ambulatory blood pressure monitoring
• eGFR < 45 ml/min/1.73 ml/min/m2 by CKD-EPI equation
• having contra-indications for MRI
• Pregnant or lactating women
• Refusal to be informed of incidental findings
• Allergy to components of contrast agent Sonovue®
• Living in an institution
• Dementia
• Type 2 diabetes
• Stroke or myocardial infarction in the past 6 months
• Blood donation in the previous 6 months
• Active oncology treatment
• Having a hierarchical relationship with the investigator or being family of the investigator