Tau accumulation and atrophy predict amyloid independent cognitive decline in aging

INTRODUCTION: Amyloid beta (A ss) and tau pathology are cross-sectionally associated with atrophy and cognitive decline in aging and Alzheimer's disease (AD). METHODS: We investigated relationships between concurrent longitudinalmeasures of A beta (Pittsburgh compound B [PiB] positron emission tomography [PET]), tau (flortaucipir [FTP] PET), atrophy (structural magnetic resonance imaging), episodic memory (EM), and non-memory (NM) in 78 cognitively healthy older adults (OA). RESULTS: Entorhinal FTP change was correlated with EM decline regardless of A beta, but meta-temporal FTP and global PiB change were only associated with EM and NMdecline in A beta+ OA. Voxel-wise analyses revealed significant associations between temporal lobe FTP change and EM decline in all groups. PiB and FTP change were not associated with structural change, suggesting a functional or microstructural mechanism linking these measures to cognitive decline. DISCUSSION: Our results show that longitudinal A beta is linked to cognitive decline only in the presence of elevated A beta, but longitudinal temporal lobe tau is associated with memory decline regardless of A beta status.