Hippocampal microstructure, but not macrostructure, mediates age differences in episodic memory

Abstract

Numerous T1- and diffusion-weighted magnetic resonance imaging (MRI) studies have separately assessed the contribution of hippocampal gray matter macrostructure (volume) and macrostructure (diffusion) to age-related declines in episodic memory, respectively. Here, we simultaneously examined the unique and joint contribution of these distinct imaging modalities in the same sample of 84 young and 66 older adults who underwent a structural MRI protocol and completed the Rey Auditory Verbal Learning Test. As expected, older age was significantly related to smaller volume and higher diffusion (intracellular, dispersion, and free) in bilateral hippocampus and to worse episodic memory performance (immediate and delayed free recall, recognition). Structural equation modelling further revealed that the age-memory relationship was significantly mediated by hippocampal diffusion, but not volume. A non-significant influential indirect effect further revealed that volume and diffusion did not jointly mediate the age-memory relationship. These findings indicate that hippocampal microstructure uniquely contributes to age-related declines in episodic memory and suggest that microstructure and macrostructure capture distinct neurobiological properties of hippocampal gray matter.