Age-related spatial discrimination: Investigating hippocampal structural foundations

Spatial discrimination is a key cognitive skill for navigating everyday environments, and a decline in spatial discrimination is considered an early sign of pathological aging. The present study aimed to explore the aging mechanisms of spatial discrimination ability for overlapping and non-overlapping routes and its hippocampal structural basis. Sixty participants (30 young adults and 30 older adults) participated in this study. They performed a passive navigation task that required learning and discriminating four different partly overlapping routes, including both overlapping and non-overlapping segments. Moreover, all participants received structural MRI scans. The volumes of the hippocampus and its four subfields, CA1 (cornu ammonis 1), CA2/3 (cornu ammonis 2/3), CA4/DG (cornu ammonis 4/dentate gyrus), and subiculum, were extracted. The results showed that older adults performed worse than young adults on all behavioral measures of spatial discrimination, including reaction time and accuracy of the whole route, overlapping route, and non-overlapping route. However, both age groups showed improved performance with increased learning blocks. Hippocampal subfields volume reductions occurred in CA4/DG (p = 0.002, η² = 0.166), while CA1 showed a marginal trend toward atrophy (p = 0.053, η² = 0.065), CA2/3 (p = 0.363, η² = 0.015) and subiculum (p = 0.142, η² = 0.038) remained preserved. Smaller hippocampal volume correlated with slower overlapping route reaction time (r = -0.399) and smaller CA4/DG correlated with lower non-overlapping route accuracy (r = 0.386). Mediation analysis revealed that hippocampus volume mediated the relationship between age and the reaction time of overlapping route, and CA4/DG volume mediated the relationship between age and the accuracy of non-overlapping route. The results demonstrate a decrement in spatial discrimination in older adults, and the structural atrophy in hippocampus and subfield CA4/DG may be the underlying mechanism of this decline. These findings demonstrate subfield-specific mediation effects in a passive navigation paradigm, highlighting CA4/DG as a potential biomarker for age-related spatial discrimination deficits and advancing understanding of the hippocampal structural basis of spatial cognitive decline.