Dynamic Amyloid PET: Relationships to Flortaucipir Tau PET Measures.

Abstract

Rationale: Measuring amyloid and predicting tau status using a single amyloid positron emission tomography (PET) study would be valuable for assessing brain AD pathophysiology. We hypothesized that early-frame amyloid PET (efAP) correlates with the presence of tau pathology because the initial regional brain concentrations of radioactivity are primarily determined by blood flow, which is expected to be decreased in the setting of tau pathology. Methods: 120 participants (63 amyloid-positive/57 amyloid-negative) with dynamic 18F-florbetapir-PET and static 18F-flortaucipir-PET scans obtained within 6 months of each other were included. These subjects were predominantly cognitively intact in both the amyloid positive (63%) and amyloid negative (93%) groups. Parameters for efAP quantification were optimized for stratification of tau PET positivity, assessed by either a tauopathy score or Braak regions. The ability of efAP to stratify tau positivity was measured using receiver operating characteristics (ROC) analysis of area under the curve (AUC). Pearson s r and Spearman s ρ were used for parametric and non-parametric comparisons between efAP and tau PET, respectively. Standardized net benefit was used to evaluate improvement in utilizing efAP as an additional co-predictor over hippocampal volumes in predicting tau PET positivity. Results: Measuring efAP within the hippocampus and summing the first 3 minutes of brain activity post-injection showed the strongest discriminative ability to stratify for tau positivity (AUC 0.67-0.89 across tau PET Braak regions) in amyloid positive individuals. Hippocampal efAP correlated significantly with a global tau-PET tauopathy score in amyloid-positive participants (r = -0.57, P < 0.0001). Compared to hippocampal volumes, hippocampal efAP showed stronger association with tau PET Braak stage (ρ = -0.58 vs. -0.37) and superior stratification of tau PET tauopathy score (AUC: 0.86 vs. 0.66, P = 0.002). Conclusion: Hippocampal efAP can provide additional information to conventional amyloid-PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.