Age differences in hippocampal subfield volumes from childhood to late adulthood

Abstract

The hippocampus is composed of distinct subfields: the four cornu ammonis areas (CA1-CA4), dentate gyrus (DG), and subiculum. The few in vivo studies of human hippocampal subfields suggest that the extent of age differences in volume varies across subfields during healthy childhood development and aging. However, the associations between age and subfield volumes across the entire lifespan are unknown. Here, we used a high-resolution imaging technique and manually measured hippocampal subfield and entorhinal cortex volumes in a healthy lifespan sample (N = 202), ages 8-82 yrs. The magnitude of age differences in volume varied among the regions. Combined CA1-2 volume evidenced a negative linear association with age. In contrast, the associations between age and volumes of CA3-DG and the entorhinal cortex were negative in mid-childhood and attenuated in later adulthood. Volume of the subiculum was unrelated to age. The different magnitudes and patterns of age differences in subfield volumes may reflect dynamic microstructural factors and have implications for cognitive functions across the lifespan. © 2015 Wiley Periodicals, Inc.

Keywords: CA1; aging; dentate gyrus; development; entorhinal cortex.

Figure 1

A distribution of the number of participants represented by decade age-bin across the lifespan. The color shading of each bar represents the distribution of each sex: black—female; gray—male.

Figure 2

Hippocampal subfields and entorhinal cortex: representative images from individuals sampled across the lifespan (ages 8–82 years). Within each individual data set, the three images are contiguous slices (0.4 × 0.4 in-plane resolution and 2-mm slice thickness) and represent the range sampled for hippocampal subfield volumetry. Image intensity gray scale is inverted to accommodate demarcation. Red—entorhinal cortex; green—subiculum; yellow—CA1–2; blue—CA3-DG.

Figure 3

The association between volume and age across the lifespan in entorhinal cortex and hippocampal subfields. All volumes are adjusted for intracranial volume (ICV; see text for details). The associations with age in the entorhinal cortex [Volume_i = 786.06 – 9.65(Age_i) + 0.08(Age_i²)] and CA3-dentate gyrus [Volume_i = 308.02 – 2.64(Age_i) + 0.02(Age_i²)] were quadratic (both p < 0.01), whereas the effect in CA1–2 was linear [p < 0.001; Volume_i = 351.76 – 0.63(Age_i)]. There were no age differences in subiculum volume (p = 0.17). Gray circles represent data points that were winsorized.