Lifespan trajectories of fornix volume and tractography: a 5.0 T MRI study

Abstract The fornix, playing a critical role in memory formation and maintenance, is recognized as an ultra-early biomarker for dementia. However, its trajectory during healthy aging remains incompletely understood. This study employed an ultra-high-field 5.0 T MRI to acquire high-resolution anatomical and multishell diffusion imaging data from 376 healthy adults aged 18 to 85. The aim was to correlate fornix characteristics with cognitive performance across multiple domains and map its lifespan trajectories. Using these data, we quantified fornix volume and tractography. Lifespan trajectories were identified by computing age-specific average patterns, which revealed distinct changes. Notably, nonlinear declines in fornix volume were observed, contrasting with fiber tract peaks between ages 18 to 40, which subsequently influenced volume-connectivity interactions. Additionally, a shift from predominant left-side to right-side fornix dominance was noted with aging. Regression analyses indicated that variations in fornix structure significantly moderated, rather than mediated, age-related differences in cognitive performance. These high-resolution imaging results provide novel insights into the role of the fornix’s morphology and structural connectivity in individual cognitive differences and aging.