Prodromal Parkinson's disease

The neurodegenerative process responsible for Parkinson's disease (PD) begins years before the level of dopamine denervation of the basal ganglia leads to the characteristic clinical phenotype of the disease. During the past 20years, numerous symptoms that may occur during the prodromal stage of the disease have been identified: subtle motor symptoms, psychocognitive disorders, sleep disorders, sensorial dysfunction, and dysautonomia. Among them, rapid eye movement sleep behaviour disorder (RBD) is one of the most specific. The follow-up of cohorts of subjects affected by this disorder has provided valuable information about the prodromal stage, including evidence of various biological or imaging biomarkers associated with the pre-clinical stage of the disease. From all the knowledge acquired about this stage of the disease, criteria for diagnosing prodromal PD have been proposed and have progressively improved in sensitivity and specificity. The strong focus on the RBD-associated prodromal stage has, however, tended to conceal other, less florid forms of prodromal PD, such as those beginning with mild cognitive impairment or mild motor symptoms, which affected subjects are less likely to notice. Here, we review the various symptoms observed in the prodromal stage of PD, progress on identifying relevant imaging and biological biomarkers, and recent insights into the pathogenesis of a disease having such a wide spectrum of presentation and progression. Advances in knowledge about prodromal PD will lead to earlier diagnosis and better identification of prognostic factors, and, subsequently, to the capacity to initiate personalized treatment and potentially slow down the degenerative process.