This review explains how Parkinson’s disease (PD) progression is best tracked with longitudinal motor ratings while recognizing that scores are shaped by both pathology and dopaminergic therapy. Pathologically, PD features Lewy pathology with early and substantial loss of nigral neurons (~50% by diagnosis; ~1.4-1.9% annual loss thereafter). This is consistent with Braak’s caudal-to-rostral staging and with additional Alzheimer-type proteins contributing to dementia in advanced disease.
Clinically, motor disability appears to rise faster just before and around diagnosis (≈5% of scale maximum per year untreated) than during long-term treated disease (≈2% per year). Levodopa produces both a short-duration response and a longer-duration response that accrues over months and can account for roughly 30% to 50% of total benefit, complicating inference about true disease trajectory. The initial mean improvement is ~40% from pretreatment disability. Advanced PD is marked by milestones (falls, hallucinations, cognitive decline, need for higher-level care) that cluster in a final approximate 5-year phase. While serial scores often look linear, late acceleration and biologic spread of α-synuclein suggest some exponential features. For trials and counseling, the authors favor defined off-state measurements and a practical three-segment view of PD (early, middle, advanced), each averaging about 5 years.
Reference: Kempster PA. Understanding the progression of Parkinson’s disease: a review. BMJ Neurol Open. 2025;7(2):e001215. doi: 10.1136/bmjno-2025-001215.
