Tau-PET and in vivo Braak-staging as a prognostic marker in Alzheimer’s disease

INTRODUCTION: Tau pathology in Alzheimer9s disease tracks clinical status more closely than beta-amyloid. Thus, tau-PET may be a promising prognostic marker for cognitive decline. Here, we systematically compared tau-PET and Braak-staging vs. amyloid-PET as predictors of cognitive decline. METHODS: We included 396 cognitively normal to dementia subjects with 18F-Flutemetamol/18F-Florbetapir-amyloid-PET, 18F-Flortaucipir-tau-PET and ~2-year cognitive assessments. Annual cognitive change rates were calculated via linear-mixed models. We determined global amyloid-PET, global tau-PET, and tau-PET-based Braak-stage (Braak 0/Braak I+/Braak I-IV+/Braak I-VI+/Braak atypical+). In bootstrapped linear regression, we assessed whether tau-PET outperformed amyloid-PET in predicting cognitive decline. Using ANCOVAs, we tested whether later Braak-stage predicted accelerated cognitive decline and determined Braak-stage-specific conversion risk to MCI or dementia. RESULTS: Global tau-PET was a better predictor of cognitive decline than global amyloid-PET (p<0.001). Advanced Braak-stage was associated with faster cognitive decline (p<0.001) and elevated clinical conversion risk. DISCUSSION: Tau-PET and Braak-staging show promise for predicting patient-specific risk of clinical AD progression.