The impact of demographic, clinical, genetic, and imaging variables on tau PET status
Rik Ossenkoppele, Antoine Leuzy, Hanna Cho, Carole H. Sudre, Olof Strandberg, Ruben Smith, Sebastian Palmqvist, Niklas Mattsson, Tomas Olsson, Jonas Jögi, Erik Stormrud, Young Hoon Ryu, Jae Yong Choi, for the Alzheimer’s Disease Neuroimaging Initiative, Adam L. Boxer, Maria Luisa Gorno‐Tempini, Bruce L. Miller, David N. Soleimani‐Meigooni, Leonardo Iaccarino, Renaud La Joie, Edilio Borroni, Gregory Klein, Michael J. Pontecorvo, Michael D. Devous, Sylvia Villeneuve, Chul Hyoung Lyoo, Gil D. Rabinovici, Oskar Hansson
Abstract
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: F]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.