Rik Ossenkoppele, Antoine Leuzy, Hanna Cho, Carole H Sudre, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Niklas Mattsson-Carlgren, Tomas Olsson, Jonas Jögi, Erik Stormrud, Young Hoon Ryu, Jae Yong Choi, Alzheimer’s Disease Neuroimaging Initiative; PREVENT-AD research group; Adam L Boxer, Maria L Gorno-Tempini, Bruce L Miller, David Soleimani-Meigooni, Leonardo Iaccarino, Renaud La Joie, Edilio Borroni, Gregory Klein, Michael J Pontecorvo, Michael D Devous Sr, Sylvia Villeneuve, Chul Hyoung Lyoo, Gil D Rabinovici, Oskar Hansson
Eur J Nucl Med Mol Imaging . 2020 Nov 19. doi: 10.1007/s00259-020-05099-w. Online ahead of print.
Publication year: 2020

Purpose: A substantial proportion of amyloid-β (Aβ)+ patients with clinically diagnosed Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI) are tau PET-negative, while some clinically diagnosed non-AD neurodegenerative disorder (non-AD) patients or cognitively unimpaired (CU) subjects are tau PET-positive. We investigated which demographic, clinical, genetic, and imaging variables contributed to tau PET status.

Methods: We included 2338 participants (430 Aβ+ AD dementia, 381 Aβ+ MCI, 370 non-AD, and 1157 CU) who underwent [18F]flortaucipir (n = 1944) or [18F]RO948 (n = 719) PET. Tau PET positivity was determined in the entorhinal cortex, temporal meta-ROI, and Braak V-VI regions using previously established cutoffs. We performed bivariate binary logistic regression models with tau PET status (positive/negative) as dependent variable and age, sex, APOEε4, Aβ status (only in CU and non-AD analyses), MMSE, global white matter hyperintensities (WMH), and AD-signature cortical thickness as predictors. Additionally, we performed multivariable binary logistic regression models to account for all other predictors in the same model.

Results: Tau PET positivity in the temporal meta-ROI was 88.6% for AD dementia, 46.5% for MCI, 9.5% for non-AD, and 6.1% for CU. Among Aβ+ participants with AD dementia and MCI, lower age, MMSE score, and AD-signature cortical thickness showed the strongest associations with tau PET positivity. In non-AD and CU participants, presence of Aβ was the strongest predictor of a positive tau PET scan.

Conclusion: We identified several demographic, clinical, and neurobiological factors that are important to explain the variance in tau PET retention observed across the AD pathological continuum, non-AD neurodegenerative disorders, and cognitively unimpaired persons.