Defining tau pathology and neurodegeneration by dual‐phase 18F‐Flortaucipir PET as diagnostic and prognostic biomarkers in a memory clinic setting

Abstract

AbstractBackground 18F‐Flortaucipir‐PET allows visualization of tau deposits (T) representing a powerful diagnostic and prognostic tool for Alzheimer’s disease (AD). Dual‐phase 18F‐Flortaucipir‐PET can also evaluate neurodegeneration (N) through the early‐phase images. We aim to assess the diagnostic and prognostic power of visual and semi‐quantitative T assessment and the potential added value of early‐phase images.MethodWe included 245 subjects from the Geneva Memory Clinic who underwent 18F‐Flortaucipir‐PET (157 with a dual‐phase protocol). Amyloid (Aβ) status was available for 207 subjects and clinical follow‐up for 135. T positivity and a Braak staging estimate were evaluated visually and semi‐quantitatively by standardized uptake value ratio (SUVr) in AD‐related regions. N status was semi‐quantitatively defined using early‐phase images as a summary metric in the AD meta‐ROI region. Receiver Operating Characteristic (ROC) analyses were applied to compare T and N discriminative power. Linear mixed‐effects models tested the prognostic values of T alone and T combined with N (T/N profiles).ResultThe mean age of the participants was 70.49±9.13 years, 52.2% were females and 55.7% were Aβ+. 53.4% of subjects had Mild Cognitive Impairment (MCI), 19.8% had dementia and 26.7% were cognitively unimpaired. All T‐assessment modalities significantly discriminated Aβ+ MCI and demented subjects from others (AUC>0.80), Aβ+ from Aβ‐ subjects (AUC>0.85), and cognitive decliners from stable individuals at follow‐up (AUC>0.79). The discriminative power of N, assessed by early‐phase images, was lower compared to T, with AUC ranging from 0.63 in discriminating Aβ+ MCI and demented subjects from others to 0.71 for discriminating Aβ+ T+ from Aβ‐ T‐ subjects. Linear mixed‐effect models showed that T+ individuals presented a significantly faster cognitive decline than the T‐ group (p<0.001) as well as T+/N+ and T+/N‐ compared to T‐/N‐ group (p<0.001), independently from T classification methods.ConclusionOur results show a similar diagnostic and prognostic power of visual and semi‐quantitative T evaluation of 18F‐Flortaucipir‐PET, proving its high potential for clinical applicability. The N status assessment with early‐phase images did not improve the prediction of cognitive decline. Its usefulness for differential diagnosis by the topographical information provided should be investigated.