Several non motor symptoms (NMS) can precede the onset of the classical motor Parkinson's disease (PD) syndrome. The existence of pre-motor and even pre-clinical PD stages has been proposed but the best target population to be screened to disclose PD patients in a pre-clinical, thus asymptomatic, stage is still matter of debate. The REM sleep behavior disorder (RBD) often affects PD patients at different stages of the disease and could precede the onset of motor symptoms by several years. However, RBD could also precede other synucleinopathies (namely, dementia with Lewy bodies and multisystem atrophy), and less frequently could be related to other neurological conditions or remain idiopathic. Moreover, not all PD patients exhibit RBD. Despite these caveats, RBD probably represents the best feature to disclose pre-motor PD patients given its high-risk of developing a full motor syndrome. Other clinical clues in the premotor stages of PD undergoing active investigation include hyposmia, depression, and autonomic dysfunction. Effective biomarkers are needed in order to improve the diagnostic accuracy in the pre-motor stage of PD, to monitor disease progression and to plan both pharmacological and non-pharmacological intervention. Functional imaging, in particular radionuclide methodologies, has been often used to investigate dopaminergic and non-dopaminergic features as well as cortical functioning in patients with RBD in its idiopathic form (iRBD) and/or associated with PD. Recently, new tracers to image α-synuclein pathologies are under development. Functional imaging in pre-motor PD, and in particular in iRBD, could improve our knowledge about the underlying mechanisms and the neurodegenerative progress of PD.
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