The Historical Development and Comparative Analysis of Diagnostic Frameworks for Corticobasal Degeneration

Background: Corticobasal degeneration (CBD) is a rare 4R tauopathy characterized by marked clinical and pathological heterogeneity. Since its original clinicopathologic description in 1968, advances in the understanding of motor, cognitive, behavioral, and language manifestations have led to substantial revisions of diagnostic concepts and criteria. Methods: A narrative review was conducted using PubMed/Medline, Embase, and Google Scholar to identify landmark publications related to the development of CBD diagnostic frameworks from 1968 through September 1, 2026. Studies were selected based on their historical significance and contribution to the clinical, neuropathologic, and conceptual evolution of CBD diagnosis. Results: The evolution of CBD diagnosis occurred in two major phases. The first phase focused on clinicopathologic characterization and establishment of the classical corticobasal syndrome phenotype. The second phase involved the development of formal diagnostic frameworks, including the Toronto criteria (1994), Office of Rare Diseases neuropathologic criteria (2002), Mayo Clinic criteria (2003), Cambridge criteria (2008), and International Consensus Criteria (2013). These frameworks progressively expanded the clinical spectrum of CBD from a predominantly motor disorder to a multisyndromic condition encompassing cognitive, behavioral, language, and progressive supranuclear palsy-like presentations. Concurrently, increasing recognition of clinicopathologic dissociation highlighted the limitations of symptom-based diagnosis and stimulated interest in biomarker-supported approaches. Conclusions: CBD diagnostic frameworks have evolved from descriptive clinicopathologic observations to comprehensive multidomain models reflecting the biological complexity of the disease. Despite substantial progress, accurate antemortem diagnosis remains challenging, underscoring the need for validated imaging, fluid, and molecular biomarkers to improve diagnostic precision and support future disease-modifying therapeutic trials.