Integrating visual assessments and quantification methods for tau PET staging

We compared visual assessments and quantification methods for tau positron emission tomography (PET) staging and evaluated plasma biomarkers and cognitive trajectories across amyloid and tau (AT) staging.

Tau PET scans from 289 Korea-Registries to Overcome Dementia and Accelerate Dementia Research (K-ROAD) participants were analyzed visually and quantitatively, with validation in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (n = 870). Plasma biomarkers and cognitive measures were evaluated across AT stages.

FreeSurfer without partial volume correction (PVC) achieved the highest area under the curve (AUC) for tau positivity (0.918), based on visual interpretation. The temporal meta-region excelled in moderate tau staging (AUC = 0.856), while the temporoparietal region performed best for advanced staging (AUC = 0.828). Quantification methods detected phosphorylated tau217 changes during intermediate transitions (e.g., A+/T- to A+/Tmod+) more effectively. Plasma biomarkers and cognitive measures progressively changed across AT stages, with consistent results in K-ROAD and ADNI cohorts.

The complementary strengths of visual and quantification methods enhance tau PET staging by effectively capturing biomarker changes and cognitive trajectories.

Quantification partially outperformed visual assessments in detecting early tau burdens. Meta-temporal and temporoparietal regions of interest excelled in early and late tau staging. Quantification methods correlated with plasma phosphorylated tau217 and cognitive decline. Findings were validated across two independent cohorts (Korea-Registries to Overcome Dementia and Accelerate Dementia Research and Alzheimer's Disease Neuroimaging Initiative). The study highlights the complementary roles of visual and quantification methods.