The impact of demographic, clinical, genetic, and imaging variables on tau PET status

Purpose A substantial proportion of amyloid-beta (A beta)+ 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 A beta+ AD dementia, 381 A beta+ MCI, 370 non-AD, and 1157 CU) who underwent [F-18]flortaucipir (n = 1944) or [F-18]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, APOE epsilon 4, A beta 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 A beta+ 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 A beta 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.

Automated summary

The study revealed that age, MMSE score, and AD-signature cortical thickness were strongly associated with tau PET positivity in Alzheimer's disease and mild cognitive impairment patients with Aβ positivity, while the presence of Aβ was the strongest predictor of a positive tau PET scan in non-AD neurodegenerative disorder patients and cognitively unimpaired individuals.