AV1451 PET IMAGING IN THE SPECTRUM OF ALZHEIMER’S DISEASE FROM CLINICALLY NORMAL TO DEMENTIA

Abstract

Tau (AV1451) PET has recently been introduced, and its ability to distinguish among clinically normal, mild cognitive impairment and dementia in the Alzheimer disease (AD) spectrum has not been established. We studied 121 clinically normal (CN) amyloid negative (A-), 54 CN amyloid positive (A+), 19 mild cognitively impaired (MCI) A-, 16 MCI A+ and 32 dementia with elevated amyloid (A+) (28 probable AD, 1 possible AD, 1 posterior cortical atrophy, and 2 logopenic PPA) (age range 52-94 yrs across entire group) with MR, 11C PIB PET and 18F-AV1451 PET imaging. Regional uptake of AV1451 was quantitated using the ratio uptake in each of 46 atlas regions scaled to the crus (SUVR). A+ was defined as PIB SUVR >1.4. Within each region of interest (ROI), we examined group-wise differences in AV1451 SUVR in CN A+ versus CN A-, MCI A+ versus CN A+, MCI A+ versus MCI A-, and dementia A+ versus MCI A+. The area under the receiver operating characteristic curve (AUROC) was calculated. We created medial temporal (MT, from amygdala, entorhinal cortex, parahippocampal), lateral temporal (LT, from fusiform, lingual, inferior temporal, middle temporal) and lateral parietal (LP, from angular, supramarginal, inferior parietal) meta-ROIs to facilitate between-group comparisons. There were significant elevations in AV1451 SUVR in MT (AUROC=0.66; p<0.001) and LT (AUROC=0.63; p=0.008) in CN A+ versus CN A-. There were significant elevations (all p≤0.001) in all 3 meta-ROIs in MCI A+ versus CN A+ (AUROCs: MT= 0.77, LT=0. 87, LP=0.81), MCI A+ versus MCI A- (AUROCs: MT=0.88, LT=0.94, LP=0.84), and in dementia A+ versus MCI A+ (AUROCs: MT=0.85, LT=0.86, LP=0.82). See Figure (PIB+= A+).