Tracking and Predicting Neurodegeneration Along the Parkinson's Disease Continuum Using Clinical, Cognitive and Advanced MRI Data

Parkinson's disease (PD) is a chronic, debilitating neurodegenerative disorder characterized by progressive motor dysfunction and various non-motor features. Better understanding and prediction of PD progression from the earliest stage will improve disease management and clinical trial design.

Idiopathic REM sleep behavior disorder (iRBD) is the most specific marker of prodromal PD, since the majority of individuals with iRBD eventually develop PD or a related synucleinopathy. Longitudinal studies have shown that the estimated risk for the clinical diagnosis of a synucleinopathy from the time of iRBD diagnosis is about 35% at 5 years, 75% at 10 years, and 90% at 14 years. Therefore, studying iRBD provides a unique window to observe neurodegenerative synucleinopathies in their prodromal stages, before parkinsonism or dementia becomes fully manifest.

This is a national, monocentric, longitudinal observational study with additional procedures. Patients with iRBD will be screened to evaluate eligibility: patients will be included if they have PSG-confirmed longstanding iRBD duration since diagnosis equal or greater than 5 years, without a clinically defined PD.

All patients undergo clinical and cognitive assessments, quantitative PSG, and MRI visits at baseline (T0) and every year for 3 years. PSG is performed to diagnose iRBD and investigate PSG changes over time. MRI evaluations investigate structural alterations and resting-state (RS) functional connectivity. Longitudinal measures of cortical/subcortical atrophy, white matter damage, and RS connectivity will be assessed.

A group of 50 healthy subjects similar for age (50-75 years old) and sex to patients with iRBD will be recruited. They will undergo clinical evaluation and PSG at study entry (to exclude sleep disorders), and motor, neuropsychological and MRI assessments at baseline and every year for 3 years.