Magnetic resonance imaging (MRI) studies using diffusion-weighted imaging (DWI) suggest that age-related cognitive decline and alterations in brain function, in healthy adults, are at least partly explained by the degradation of white matter (WM) pathways connecting distributed brain regions. Studies of younger adults and animal models suggest that more precise estimates of WM connectivity may be achieved by higher resolution, relative to standard spatial resolution, DWI. Here, in a cross-sectional study of healthy adults across the lifespan (n = 140; ages 18-88 years; 72 females), we compared age-related differences in measures of WM structural connectivity from standard (1.5 mm3 voxels; 3.375 μl volume) and high-resolution (1 mm3; 1μl volume) DWI, and their ability to explain age-related differences in functional connectivity and cognition. We assessed cognition using tests of memory, executive function, and perceptual-motor speed, and assessed structural (DWI) and functional (resting-state functional MRI) connectivity using graph theory. Results revealed more pronounced age-related decreases in structural connectivity for sensorimotor, ventral attention, and subcortical networks for high-resolution than standard DWI. Age-related decreases in functional connectivity were evident across the brain and mediated by high-resolution structural connectivity in the default mode network. Age-related decline in fluid cognition was mediated by within-network connectivity from only high-resolution DWI, but by a combination of high-resolution and standard DWI for between-network connectivity. Thus, relative to standard DWI, high-resolution DWI may better capture age-related differences in WM connectivity and their constraint on age-related alterations in brain function and cognitive performance.
Jenna L Merenstein, Allen W Song, David J Madden, High-resolution structural connectivity mediates age-related differences in functional connectivity and fluid cognition, Brain Communications, 2025;, fcaf376, https://doi.org/10.1093/braincomms/fcaf376