Predictors of cerebral tauopathy in individuals with normal cognition and amnestic mild cognitive impairment (aMCI): results from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (4594)

Objective: To identify predictive features of tauopathy defined by PET imaging across the AD spectrum. Background: The time course of tau aggregation and its dynamic relationship to other pathophysiological features in the various stages of AD is incompletely characterized. Design/Methods: We selected 508 cognitively unimpaired elderly and 213 participants with aMCI and 31 individuals with dementia (AD) from ADNI. Participants were classified as having normal (T−) or abnormal (T+) tau using the cutoff point of standard uptake value ratio (SUVr) 1.40 in the tau meta-ROI (entorhinal, amygdala, parahippocampal, fusiform, inferior temporal, and middle-temporal-ROIs normalized to cerebellar-crus). Stepwise multivariate logistic regression was carried out to identify predictors of tau positivity for the whole population, and CN and aMCI subgroups, first using demographic, clinical and genetic features and then adding imaging features. Results: Positive tau PET scans were detected in 7.9% of CN, 26.8% of aMCI, and 67.7% of AD individuals. In the entire sample, predictors of tau positivity included at least one ApOE4 allele, clinical dementia rating sum of boxes (CDR-SB), Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog). Imaging biomarkers improving prediction included hippocampal volume and Aβ positivity on PET. Predictors of tauopathy were different for each diagnostic subgroup: Among CN individuals age and CDR-SB were predictors of tauopathy and of the imaging markers only Aβ PET contributed significantly. In the aMCI group, APOE4, ADAS-cog, and logical memory were predictors of tau positivity with incremental prediction from hippocampal volume, and Aβ burden. Conclusions: Aβ positivity seems to precede substantial tau deposition and is the main predictor of tau positivity across the AD spectrum. Neurocognitive scores, APOE4 alleles, and neurodegeneration biomarkers may help with the identification of tau positive individuals in later stages of disease. Disclosure: Dr. Ezzati has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. The institution of Dr. Ezzati has received research support from NIA. The institution of Dr. Ezzati has received research support from Alzheimer’s Association. The institution of Dr. Ezzati has received research support from Cure Alzheimer’s Fund. Danielle Harvey has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for PLOS ONE. Danielle Harvey has received research support from NIH. KELLEN Petersen has nothing to disclose. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Allergan. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biohaven. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Lundbeck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for GlaxoSmithKline. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Vedanta. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Satsuma. Dr. Lipton has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lilly. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Grifols. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Allergan. Dr. Lipton has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Amgen. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biohaven. Dr. Lipton has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eli Lilly. Dr. Lipton has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Lipton has received stock or an ownership interest from eNeura. Dr. Lipton has received stock or an ownership interest from Biohaven. Dr. Lipton has received stock or an ownership interest from CtrlM Health. The institution of Dr. Lipton has received research support from Teva. The institution of Dr. Lipton has received research support from Amgen. The institution of Dr. Lipton has received research support from Allergan. The institution of Dr. Lipton has received research support from Gammacore. The institution of Dr. Lipton has received research support from Axsome. The institution of Dr. Lipton has received research support from Charleston Labs. The institution of Dr. Lipton has received research support from Eli Lilly. The institution of Dr. Lipton has received research support from Satsuma. The institution of Dr. Lipton has received research support from NIH . The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NINDS. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from NIA. The institution of Dr. Lipton has received research support from NIH. The institution of Dr. Lipton has received research support from Veterans Administration. The institution of Dr. Lipton has received research support from NIH. Dr. Lipton has received publishing royalties from a publication relating to health care.