Hippocampal atrophy over two years in relation to tau, amyloid-β and memory in older adults

In this longitudinal brain imaging study, we aimed to characterize hippocampal tau accumulation and subfield atrophy relative to cortical amyloid-β and memory performance. We measured tau-PET in regions associated with Braak stages I to VI, global amyloid-PET burden, hippocampal subfield volumes and memory assessments from 173 participants aged 55–85. Eighty-six of these participants were tested again two years later. Tau-PET change in the Braak II region, corresponding to the hippocampus and the entorhinal cortex , was significantly associated with the cornu ammonis 1 (CA1) atrophy and memory score. This CA1 atrophy did not significantly mediate the association between tau and memory, nor did global amyloid-PET burden correlate with tau-PET changes in the Braak II region. Longitudinal hippocampal tau accumulation is amyloid-β-independent and co-localized with subfield atrophy. As tau-associated memory decline seems to be independent from hippocampal atrophy, other mechanisms could contribute to the deficit. • Hippocampal and entorhinal tau accumulation is amyloid-β-independent. • Baseline tau load is not specific to local longitudinal hippocampal atrophy. • CA1 and subiculum atrophy mirror longitudinal hippocampal tau pathology. • Challenge the hippocampal volume's mediation of the tau-memory link. • Memory decline is tied to tau beyond hippocampal subfields atrophy.