Anterior and posterior hippocampus macro‐ and microstructure across the lifespan in relation to memory—A longitudinal study

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 seen across development and aging. The hippocampus 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, 1,790 cognitively healthy participants, 4.1–93.4 years of age, underwent a total of 3,367 MRI examinations and 3,033 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 (macrostructure), and diffusion tensor imaging to measure mean diffusion (MD, microstructure) 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. An aHC–pHC difference was also observed for volume, with pHC changing relatively more with higher age. All regions showed age‐dependent relationships with episodic memory. aHC micro‐ and macrostructure was significantly related to verbal memory independently of age, but the relationships were still strongest among the older participants. We suggest that memory processes supported by each sub‐region improve or decline in concert with volumetric and microstructural changes in the same age‐period. Future research should disentangle the lifespan relationship between changes in these structural properties and different memory processes, encoding versus retrieval in particular, as well as other cognitive functions depending on the hippocampal long‐axis specialization.

Age‐related alterations in functional connectivity along the longitudinal axis of the hippocampus and its subfields

“…First, we divided the template‐space brain into equally spaced slices along a roughly 30° forward‐facing angle (aligned with the angle of the hippocampus), resulting in six segments with roughly the same number of voxels, separated by small gaps to reduce partial volume effects. The first three segments corresponding the anterior hippocampus and the last three segments corresponding to the posterior hippocampus were consistent with the A‐P divide employed by other groups (Blum et al, 2014; Langnes et al, 2020). Then we warped this template into subject‐specific space and multiplied it by the subject‐specific segmentations, creating even segmentations along the longitudinal axis of the hippocampus.…”

Hippocampus shape across the healthy lifespan and its relationship with cognition

“…SA results are in agreement with previous findings demonstrating a stronger impact of aging in the posterior hippocampus (Malykhin et al 2017; Langnes et al 2020). Additionally, evidence of anterior/posterior (AP) anatomical and functional differences in the hippocampus have been highlighted by various studies.…”

Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers

“…APOE allele ε4 carriership was defined as APOE alleles ε2/ε4, ε3/ε4, or ε4/ε4. For details on genotyping methods, see the study‐specific details 18–25 …”