Observational, prospective, monocentric study to assess clinical features, imaging and biologic biomarkers in Parkinson disease (PD) patients and rate of progression compared to healthy controls (HC) and subjects at risk to develop PD.

The primary objective of this study is to identify clinical, imaging and biologic markers of PD onset and progression for use in clinical trials of disease-modifying therapies.

ICEBERG will be a four-year natural history study of de novo idiopathic PD patients, healthy controls, and subjects at risk to develop PD (idiopathic Rem Behavior Disorder -iRBD, and probants of patients with PD genetically confirmed).

All subjects will be comprehensively assessed at baseline and every year thereafter. Subjects will undergo clinical (motor, neuropsychiatric, sleep, ocular and cognitive evaluations) and imaging assessments. Blood (including a DNA sample), stools, skin biopsy and cerebral spinal fluid (CSF) samples will be collected.

Inclusion Criteria:

• All subjects: Male or female age 18 years and older, MMSE score > 26, negative pregnancy test in potentially child-bearing women (contraindication to SPECT with DatScan).
• Idiopathic Parkinson disease subjects: diagnosis confirmed according to UK Parkinson's Disease Society Brain Bank criteria (UKPDSBB); disease duration less than 3 years.
• Genetic Parkinson disease subjects: parkinson diagnosis confirmed and mutation in parkin, LRRK2, SNCA or GBA genes.
• Prodromal subjects: subjects with identified relative with PD genetically confirmed or subjects with diagnosis of idiopathic Rem sleep Behavior Disorder (iRBD); neurological examination normal (no signs of parkinsonism).
• Healthy subjects: neurological examination normal

Exclusion Criteria:

• All subjects: Psychiatric disorder or any progressive life-threatening disease, impairment precluding appropriate information and instructions given concerning participation to the study; contra-indication to MRI or SPECT scan.
• Parkinson disease subjects: no dopamine transporter deficit at SPECT scan; parkinsonism induced by neuroleptics; neuroleptics intake within 6 months; atypical parkinson syndrom (MSA, PSP, CBD...)
• Parkinson disease subjects with mutation in Parkin, LRRK2, SNCA or GBA gene: atypical parkinson disease syndromes due to either drugs (e.g., metoclopramide, flunarizine, neuroleptics) or metabolic disorders (e.g., Wilson's disease), encephalitis or degenerative diseases (e.g., progressive supranuclear palsy) or currently taking neuroleptics or has taken neuroleptics within 6 months of baseline or any biological anomaly.

Patients with recent onset of Parkinson Disease (less than 3 years since diagnosis) compared to subjects at risk to develop Parkinson Disease and healthy controls