Improved Correlation of18F-Flortaucipir PET SUVRs and Clinical Stages in the Alzheimer Disease Continuum with the MUBADA/PERSI-Based Analysis

Abstract

The Alzheimer disease (AD) continuum is a neurodegenerative disorder with cognitive decline and pathologic changes. Tau PET imaging can detect tau pathology, and 18 F-fl ortaucipir PET imaging is expected to visualize progression through the stages of AD, for which quantitative assessment is essential. Two measurement methods, statistically de fi ned multiblock barycentric discriminant analysis (MUBADA)/parametric estimation of reference signal intensity (PERSI) and anatomically de fi ned tau meta – volume of interest (VOI)/cerebellar gray matter (CGM) for SUV ratio (SUVR), were compared in this study to assess their relationship to AD clinical stage using 2 open multicenter PET databases. Methods: Data were selected for 106 cases from 2 databases, AMED Pre-clinical AD study (AMED-PRE) ( n 5 15) and Alzheimer Disease Neuroimaging Initiative 3 ( n 5 91). The data of the participants were categorized into 4 groups based on the clinical criteria. Tau PET imaging was conducted using 18 F-fl ortaucipir, and the 2 SUVR measurement methods, MUBADA/PERSI and tau meta-VOI/CGM, were compared among different clinical categories: amyloid-negative cognitively normal, preclinical AD, amyloid-negative mild cognitive impairment (MCI), and amyloid-positive MCI. Results: Signi fi cant differences were found between cognitively normal and preclinical AD, as well as between cognitively normal and amyloid-positive MCI and between amyloid-negative MCI and -positive MCI in SUVR derived by MUBADA/PERSI, whereas SUVR by tau meta-VOI/CGM did not provide signi fi cant differences between any pair. The tau meta-VOI/CGM method consistently provided higher SUVRs and larger individual variations than MUBADA/PERSI, with a mean SUVR difference of 0.136 for the studied databases. Conclusion: MUBADA/PERSI provided the SUVR of 18 F-fl ortaucipir uptake with better association with the clinical severity of the AD continuum and with smaller variability. The results support the usefulness of MUBADA/PERSI as a quantitative measure of 18 F-fl ortaucipir uptake in multicenter studies using different PET systems and scanning methods. However, limitations of the study include the small sample size and the unbalanced distribution among clinical categories in the AMED Preclinical AD study database.