From Prodromal to Overt Parkinson's Disease: Towards a New Definition in the Year 2040.

The field of prodromal PD is still in its infancy, and at the cusp of major advances. This article summarizes where we are, and most importantly where we need to go in order for the promise of prodromal PD to be realized. In the immediate future, the criteria need to be updated with additional markers and disseminated broadly. In the near future, they need to better incorporate changes in likelihood ratio with age and sex, combine markers in novel ways using big data approaches, identify subtypes, and incorporate better higher-specificity markers as they are discovered. Integration of smartphone/wearable markers and biomarkers of progression from the prodromal phase will allow development of neuroprotective trials in early stages. By 2040, it is hoped that prodromal criteria will be incorporated into active neuroprotective treatment programs, allowing a program of population-based screening followed by early treatment and ultimately the prevention of clinical PD from ever becoming manifest.