Relationship between [18F]flortaucipir PET visual patterns and neurodegeneration

Background: The introduction of tau positron emission tomography (PET) ligands has allowed for the in vivo assessment of tau pathology in Alzheimer’s disease (AD). The recent development and FDA approval of [18F]flortaucipir (FTP) reader guidelines has enabled standardized visual assessment of FTP PET scans as showing negative, moderate or advanced AD tau patterns, thereby facilitating implementation of FTP scans in clinical practice. Although various studies have reported associations between regional FTP signal and neurodegeneration, the relationship between the standardized visual FTP AD patterns and markers of neurodegeneration has not yet been studied. This study aims to understand how FTP AD visual patterns relate to markers of neurodegeneration from structural MRI and FDG-PET scans. Specifically, it focusses on characterizing regional neurodegeneration associated with the moderate AD pattern, both in cognitively normal (CN) and cognitively impaired participants (CI). Method: Participants from five cohorts were included: the Alzheimer’s Disease Neuroimaging Initiative, Harvard Aging Brain Study, A4 study, the Geneva Memory Clinic cohort and AVID’s A05 study. These cohorts include CN participants, mild cognitively impaired and AD dementia patients who have available FTP, MRI and/or FDG scans, a subset also received follow-up MRI scans. Furthermore, Centiloid values are available for all participants to quantitatively determine amyloid-β (Aβ) positivity. All FTP scans are currently independently evaluated by three trained readers, blinded to clinical and imaging information. Majority read is used to assign scans to the negative, moderate or advanced AD tau pattern groups. Result: A total of 1948 participants underwent baseline FTP PET and MRI scans, a subset of 462 participants also underwent FDG-PET scans. Between-group differences in MRI- and FDG-derived patterns of neurodegeneration are evaluated cross-sectionally. In addition, the value of FTP AD patterns for predicting longitudinal neurodegeneration using MRI-derived atrophy measures is assessed using Linear Mixed Models. All analyses are conducted separately for CN and CI participants, as well as stratified by Aβ (positive vs. negative) status. NB. Results of these analyses will be presented during the conference. Conclusion: This study will contribute to our understanding of the clinical relevance and prognostic value of the moderate and advanced FTP AD patterns in CN and CI individuals.