IMAGE PATTERNS AND CLINICAL PHENOTYPES ASSOCIATED WITH FASTEST INCREASE OF TAU BURDEN MEASURED BY LONGITUDINAL [18F]-AV-1451 (T807) PET STUDIES

Recent findings suggest the potential utility of the PET radiotracer 18F-AV-1451 (18F-T807) to detect longitudinal change in tau burden. The goal of this study is to identify subgroup(s) of subjects who may show the most rapid longitudinal change in 18F-AV-1451 signal, and examine baseline clinical phenotypes and image patterns associated with these subgroups. We examined 18F-AV-1451 PET images acquired from 60 amyloid-positive MCI and AD subjects who underwent both baseline and approximately 9 month follow-up scans. As “progressors”, we considered a group with the highest 25% change (follow-up minus baseline) in global SUVR from a large ROI weighted predominantly by cortical regions and using cerebellum crus as a reference (dSUVR). For each group, the baseline clinical characteristics and imaging metrics (estimated Braak stage (Schwarz AJ et al, Brain, 2016, in press), estimated hippocampus:cortex ratio (Murray ME et al, Lancet Neurology, 2011), global and regional SUVR) were estimated. Clinical phenotypes for progressors (8 AD, 7 MCI, mean dSUVR=0.16) differed from those for non-progressors (16AD, 29 MCI, mean dSUVR=0.00). Progressors were on average younger and had higher ADAS-Cog at baseline (Figure 1). Progressors were also separated by baseline 18F-AV-1451 imaging metrics, having higher global SUVR, more advanced in vivo estimated Braak stage (4-6 vs 3-4) and lower hippocampus:cortex SUVR ratio (Figure 1). Baseline SUVR for individual regions (temporal, occipital, parietal, frontal) also separated two groups. Specifically, minimal frontal SUVR was observed for non-progressors (95% CI=1.02-1.12) while progressors demonstrated an elevated SUVR in frontal lobe (95% CI=1.21-1.52). The dichotomization based on the highest 50% increase in global dSUVR resulted in directionally similar but smaller differences between progressors (13 AD, 17 MCI, mean dSUVR=0.09) and non-progressors (11AD, 19 MCI, mean dSUVR=-0.01).