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

Deciphering the Mechanisms of Central Blood Pressure Regulation in Patients With Parkinson Disease Associated With Orthostatic Hypotension: A 2-phase Observational Study With Healthy Participants and Patients With Parkinson's Disease

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.

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 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