Longitudinal trajectory of Amyloid-related hippocampal subfield atrophy in nondemented elderly

Hippocampal atrophy and abnormal β-Amyloid (Aβ) deposition are established markers of Alzheimer's disease (AD). Nonetheless, longitudinal trajectory of Aβ-associated hippocampal subfield atrophy prior to dementia remains unclear. We hypothesized that elevated Aβ correlated with longitudinal subfield atrophy selectively in no cognitive impairment (NCI), spreading to other subfields in mild cognitive impairment (MCI). We analyzed data from two independent longitudinal cohorts of nondemented elderly, including global PET-Aβ in AD-vulnerable cortical regions and longitudinal subfield volumes quantified with a novel auto-segmentation method (FreeSurfer v.6.0). Moreover, we investigated associations of Aβ-related progressive subfield atrophy with memory decline. Across both datasets, we found a converging pattern that higher Aβ correlated with faster CA1 volume decline in NCI. This pattern spread to other hippocampal subfields in MCI group, correlating with memory decline. Our results for the first time suggest a longitudinal focal-to-widespread trajectory of Aβ-associated hippocampal subfield atrophy over disease progression in nondemented elderly.