18F]AV1451 BINDING POTENTIAL IN RELATION TO AMYLOID STATUS AND COGNITION IN SUBJECTS WITH SUBJECTIVE COGNITIVE DECLINE

Abstract

Subjective cognitive decline (SCD) is associated with an increased risk of cognitive decline and might reflect the earliest changes associated with Alzheimer's disease (AD). Neuropathological studies have shown that tau accumulation is closely linked to cognitive decline. Using [18F]AV1451 PET it is now possible to quantify tau pathology in vivo. The aim of this study was to investigate specific [18F]AV1451 binding in relation to amyloid status and neuropsychological performance in cognitively normal subjects with SCD. 23 subjects with SCD (age 66±7, 52% female, MMSE: 28±1) underwent both 90 minute dynamic [18F]florbetapir (amyloid) and 130 minute dynamic [18F]AV1451 (tau) PET scans, and an extensive neuropsychological test battery. [18F]Florbetapir scans were read visually as positive or negative for presence of cerebral amyloid. Reference parametric mapping (RPM) with cerebellar grey matter as reference region was used to calculate [18F]AV1451 binding potential (BPND). Results were analysed for 1) medial temporal lobe (MTL), known as the first region to harbour tau pathology in aging, 2) a global region (neocortex), and 3) putamen, a region thought to represent “off-target” binding. Raw neuropsychological test scores were converted into z-scores and combined into composite scores for episodic memory. [18F]Florbetapir positive subjects (n=7) showed higher [18F]AV1451 BPND than [18F]florbetapir negative subjects (n=16) in MTL (0.21±0.18 vs -0.04±0.05, p<0.01) and neocortex (0.14±0.06 vs 0.02±0.04, p<0.001). Adjusted for age, sex and education, lower episodic memory scores were, although at trend level, associated with higher [18F]AV1451 BPND in MTL (β=-0.52, p=0.06) and neocortex (β=-0.49, p=0.07), but not putamen (β=-0.25, p=0.43). Across all subjects, regardless of amyloid status, higher age correlated with higher [18F]AV1451 BPND in the putamen (Pearson's r = 0.66, p<0.01), but not with [18F]AV1451 BPNDin MTL and neocortex. These preliminary data suggest that tau load in AD specific regions of subjects with SCD is higher in amyloid positive than in amyloid negative subjects. In addition, tau accumulation in MTL and neocortex might be associated with poorer episodic memory performance. This highlights the potential of tau PET to capture early and subtle cognitive changes in subjects with SCD.