Longitudinal hippocampal atrophy is associated with cognitive decline independently of amyloid and tau in neocortex

摘要: Background Hippocampal volume (HV) atrophy is a well‐known biomarker of cognitive impairment. However, it is not specific for Alzheimer’s disease (AD). To disentangle the contributions of AD and other neuropathologies to cognitive decline, we investigated the longitudinal associations between HV and cognition, adjusting for Aβ and tau in participants from the Harvard Aging Brain Study who were clinically normal (CN) at inclusion. Methods Serial MRI (HV [1.3‐7.0y], PiB‐PET (Aβ, [1.9‐8.5y]), Flortaucipir‐PET (tau, [0.8‐6.0y]), and the Preclinical Alzheimer Cognitive Composite (PACC, [3.0‐8.8y]) were observed over an average five‐year follow‐up in 128 CN participants, including ten who progressed to symptomatic AD during the study. Longitudinal HVs were processed using Freesurfer v.6 and adjusted for intracranial volume. PiB was measured in a neocortical aggregate, Flortaucipir in inferior temporal (IT …