Age-associated trajectories of hippocampus subregion volumes from childhood through later adulthood

Abstract

The hippocampus has been widely implicated in the neurobiology of neurologic and psychiatric disorders. This structure is heterogeneous, however, and comprised of multiple subregions that have different connectivity patterns and functions. Better understanding how these subregions are affected by age and their relationship with neurocognition could provide information regarding how alterations in normal trajectories play a role in disease and cognitive dysfunction. Using natural splines we modeled the trajectory of 4 hippocampus subregions (i.e., CA composite, DG composite, tail and subiculum) derived from automated segmentation of magnetic resonance images using FreeSurfer in a cohort of 674 (440F/234M) healthy individuals ranging in age from 6 to 85 years. Following adjustment for covariates the best fitting model for all subregions was a spline with 2 degrees of freedom, which included one internal knot and two boundary knots. The peak age at which all subregions achieved maximum volume occurred in the fourth decade of life. Prior to the peak age there was no significant mediating effect of hippocampus subregion volume on the relationship between age and memory. Following the peak age, however, hippocampal subregions partially mediated the relationship between age and memory performance with the proportion mediated ranging from 11 % (subiculum) to 17 % (CA composite), but with no significant effects observed for the tail. These findings provide novel information regarding the trajectory of individual hippocampus subregion volumes across the age span and suggest they mediate the relationship between age and memory performance.