Differential atrophy along the longitudinal hippocampal axis in Alzheimer’s disease

Abstract

AbstractBackgroundAlzheimer’s disease (AD) is a progressive neurodegenerative disorder that primarily affects the hippocampus. Since hippocampal studies have highlighted a differential subregional regulation along its longitudinal axis, a more detailed analysis addressing subregional changes along the longitudinal hippocampal axis has the potential to provide new relevant biomarkers.MethodThis study analysed structural brain MRI data of 600 participants (aged 55‐92 years‐old) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Hippocampi of cognitively normal (CN) subjects (n=200), mild cognitively impaired (MCI) subjects (n=200) and AD patients (n=200) were segmented with Freesurfer v6.0 and sub‐segmented along its longitudinal axis in anterior, intermediate and posterior sub‐divisions using an in‐house algorithm.ResultTotal hippocampal volume normalized to intracranial volume (ICV) negatively correlated with age in all groups. Standardized residuals from the linear regression of normalized hippocampal volume by age were then calculated, showing that the mean relative atrophy corrected for the aging effect was higher in CN (µ = 0.54) than in MCI (µ = 0.13), and lower in AD (µ = ‐0.67), with significant differences between all groups (p < .001 in all comparisons). Both anterior, intermediate and posterior hippocampus negatively correlate with age in all groups, with no significant differences between them. However, when normalizing to total hippocampus, only CN subjects show a significant positive correlation (r = 0.15, p = .03) between anterior sub‐division and age, and only CN (r = ‐0.27, p < .001) and MCI (r = ‐0.18, p = .01) posterior hippocampus negatively correlate with age. The longitudinal ratio of hippocampal atrophy (anterior sub‐division divided by the posterior one) shows a significant increase with age in CN (r = 0.25, p < .001) and MCI (r = 0.15, p = .04) but not in AD (r = ‐0.07, p = .35).ConclusionNormal aging affects the hippocampus differently along its longitudinal axis: its posterior aspect shows more atrophy and the anterior one becomes relatively more prominent. In AD, this antero‐posterior gradient is disrupted early on, and hippocampal atrophy occurs in a similar manner along its longitudinal axis from late‐adulthood to older ages.