Abstract There is evidence for a hippocampal long axis anterior-posterior (AP) differentiation in memory processing, which may have implications for the changes in episodic memory performance typically seen across development and aging. The hippocampal formation shows substantial structural changes with age, but the lifespan trajectories of hippocampal sub-regions along the AP axis are not established. The aim of the present study was to test whether the micro- and macro-structural age-trajectories of the anterior (aHC) and posterior (pHC) hippocampus are different. In a single-center longitudinal study, 1790 cognitively healthy participants, 4.1-93.4 years of age, underwent a total of 3367 MRI examinations and 3033 memory tests sessions over 1-6 time points, spanning an interval up to 11.1 years. T1-weighted scans were used to estimate the volume of aHC and pHC, and diffusion tensor imaging to measure mean diffusion (MD) within each region. We found that the macro- and microstructural lifespan-trajectories of aHC and pHC were clearly distinguishable, with partly common and partly unique variance shared with age. aHC showed a protracted period of microstructural development, while pHC microstructural development as indexed by MD was more or less completed in early childhood. In contrast, pHC showed larger unique aging-related changes. A similar aHC – pHC difference was observed for volume, although not as evident as for microstructure. All sub-regions showed age-dependent relationships to episodic memory function. For aHC micro- and macrostructure, the relationships to verbal memory performance varied significantly with age, being stronger among the older participants. Future research should disentangle the relationship between these structural properties and different memory processes – encoding vs. retrieval in particular – across the lifespan.

Lifespan trajectories and relationships to memory of the macro- and microstructure of the anterior and posterior hippocampus – a longitudinal multi-modal imaging study