Table 1 Conceptual stages of Parkinson’s disease (PD)

Phase 1—preclinical PD

No clinical signs or symptoms

PD-specific pathology assumed to be present

Supported by biomarkers (genetic, molecular, and/or imaging)

Phase 2—prodromal PD

Early nonmotor symptoms ± early subtle motor symptoms

Extranigral PD pathology (Braak stages 1 and 2) ± nigral PD pathology (< 40%–60% cell loss; Braak Stage 3)

Research criteria defined based on clinical nonmotor markers (± motor markers) and nonclinical biomarkers. There may be various levels of certainty [18]; probable prodromal PD defined at ≥ 80% probability (sufficiently certain for disease-modification trials) [24] and possible prodromal PD (lower, but still substantial likelihood, e.g., 30%–80%)

Phase 3—clinically established PD

Classical motor manifestations are present

Nigral PD pathology (> 40%–60% cell loss; Braak stages 3 to 6)

Current clinical diagnostic criteria based on motor syndrome are met [1]; ± a variety on nonmotor symptoms may be present due to extranigral extension of PD pathology