Layered classification in Parkinson’s disease: a content analysis of clinical, prodromal, and biological criteria evolution
TL;DR
How major PD criteria and research frameworks have justified diagnostic change and redistributed the roles of clinical signs, biomarkers, genetics, and prodromal markers is clarified.
Abstract
Background Parkinson’s disease (PD) is no longer described through a single diagnostic vocabulary. Clinical criteria, prodromal probability models, and biological research classifications now operate in parallel after the 2024 NSD-ISS and SynNeurGe proposals. Objective To clarify how major PD criteria and research frameworks have justified diagnostic change and redistributed the roles of clinical signs, biomarkers, genetics, and prodromal markers. Methods We conducted a targeted document-based qualitative content analysis of eight purposively selected landmark PD criteria or criteria-adjacent framework documents, with the 1988 UK Brain Bank/Lewy body source retained as a historical lineage anchor. Document-declared aims and perceived diagnostic problems were coded with a prespecified framework, and twelve diagnostic elements were assigned interpretative ordinal scores according to their document-specific textual roles. Results Within the selected corpus, stated priorities shifted from clinicopathological specificity, standardization, and differential diagnosis toward early identification, biomarker integration, staging/subtyping, and trial readiness. Diagnostic-element roles moved from motor signs, exclusions, and dopaminergic response toward RBD/olfaction in prodromal probability frameworks and toward α-synuclein SAA, dopaminergic imaging, and genetics in 2024 biological research frameworks. The analyzed documents indicated materially different 2024 architectures: NSD-ISS emphasized biological definition and integrated staging, whereas SynNeurGe used a multidimensional S/N/G structure. Conclusion Our analysis suggests that contemporary PD classification can be understood as a layered architecture rather than a simple replacement sequence. Clinical criteria remain necessary for care, prodromal criteria support early-risk research, and biological frameworks require longitudinal, pathological, technical, ethical, and global-access validation before clinical translation.