Hippocampal subfields and limbic white matter jointly predict learning rate in older adults

Abstract

Age-related memory impairments have been linked to differences in structural brain parameters, including cerebral white matter (WM) microstructure and hippocampal (HC) volume, but their combined influences are rarely investigated. In a population-based sample of 337 older participants 61-82 years of age (Mage=69.66, SDage=3.92 years) we modeled the independent and joint effects of limbic WM microstructure and HC subfield volumes on verbal learning. Participants completed a verbal learning task over five learning trials and underwent magnetic resonance imaging (MRI), including structural and diffusion scans. We segmented three HC subregions on high-resolution MRI data and sampled mean fractional anisotropy (FA) from bilateral limbic WM tracts identified via deterministic fiber tractography. Using structural equation modeling, we evaluated the associations between learning rate and latent factors representing FA sampled from limbic WM tracts, and HC subfield volumes, as well as their latent interaction. Results showed limbic WM and the interaction of HC and WM - but not HC volume alone - predicted verbal learning rates. Model decomposition revealed HC volume is only positively associated with learning rate in individuals with higher levels of WM anisotropy. We conclude that structural characteristics of limbic WM regions and HC volume jointly contribute to verbal learning in older adults.