Two-year changes in hippocampal subfield volumes are age-dependent across the lifespan

The hippocampus (Hc), which is crucial for memory across the lifespan, is comprised of distinct subfields: dentate gyrus (DG), Cornu Ammonis (CA) sectors 1-3, and subiculum. Cross-sectional studies show that Hc subfield volumes exhibit a differential association with age across the lifespan. However, the evidence of age-related changes and individual variability in developmental trajectories is sparse. We examined changes in Hc subfield volumes in a large normative lifespan sample (N = 474 at baseline, n = 189 at follow-up; mean interval = 2.5 years) while comparing patterns of change in children (ages 5-10.9 years), adolescents (ages 11-18.9 years), young (ages 19-35.9 years), middle-aged (ages 36-55.9 years), and older adults (ages 56-73.9 years). In a pooled lifespan sample, we observed no mean change in Hc subfield volumes. Nonetheless, there were significant individual differences in change for all subfields that depended on the baseline age. A general tendency for volume gain in young individuals attenuated in adulthood and shifted toward loss in late lifespan segments. Across age groups, CA1-2 volume increased into young adulthood, whereas DG-CA3 and subiculum volumes remained stable and declined significantly after age of 55 years. Thus, our results reveal age-related differences in Hc subfield volume changes over nearly the entire human lifespan. Our findings have significant implications for models of neural development and aging and for understanding lifespan trajectories of memory.