Dynamic Amyloid PET: Relationships to ¹⁸F-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 18 Fflorbetapir-PET and static 18 F-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 copredictor 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). Conclusions:Hippocampal efAP can provide additional information to conventional amyloid-PET, including estimation of the likelihood of tau positivity in amyloid-positive individuals.

Plasma Core Alzheimer’s Disease Biomarkers Predict Amyloid Deposition Burden by Positron Emission Tomography in Chinese Individuals with Cognitive Decline

“…Interestingly, plasma P-tau181 and P-tau181/T-tau ratio were negatively correlated with Aβ deposition in the hippocampus and parahippocampal cortex in our investigation, which indicated the different degrees of tau and Aβ deposition in the hippocampus and parahippocampal cortex. Previous studies had shown that a decrease in hippocampal early-frame amyloid PET was strongly in inverse association with tau PET Braak stage in Aβ+ individuals . More research studies may be needed to confirm such a characteristic in a larger cohort.…”

“…Previous studies had shown that a decrease in hippocampal early-frame amyloid PET was strongly in inverse association with tau PET Braak stage in Aβ+ individuals. 33 More research studies may be needed to confirm such a characteristic in a larger cohort.…”

Multimodality imaging of neurodegenerative disorders with a focus on multiparametric magnetic resonance and molecular imaging

“…While the literature at the time is sparse, coupling these techniques with amyloid PET imaging has shown promising results in terms of diagnostic accuracy, with sensitivity and specificity near or surpassing 90% [ 63 ]. Dynamic imaging can also be performed immediately following the bolus to estimate cerebral blood flow, with a report suggesting decreased early time frame amyloid activity correlating with tau retention [ 64 ].…”

Measurement of neurodegeneration using a multivariate early frame amyloid PET classifier

“… 25 , 29 Recently, discrimination between cognitively normal tau‐negative versus tau‐positive groups was demonstrated using EFA hippocampal values. 30 …”

“…25,29 Recently, discrimination between cognitively normal tau-negative versus tau-positive groups was demonstrated using EFA hippocampal values. 30 We previously demonstrated that an optimized FDG PET multivariate image classifier can improve detection of AD-related neuronal decline and prediction of subsequent clinical worsening in preclinical and prodromal AD. [31][32][33][34] In the present work, we evaluated the ability of an EFA classifier to provide a similar measure of neurodegeneration and to discriminate between cognitively normal amyloid-negative controls and early prodromal as well as later AD stages, and to predict rate of subsequent clinical decline.…”