High-resolution structural connectivity mediates age-related differences in functional connectivity and fluid cognition

Magnetic resonance imaging studies using diffusion-weighted imaging 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 pathways connecting distributed brain regions. Studies of younger adults and animal models suggest that more precise estimates of white matter connectivity may be achieved by higher resolution, relative to standard spatial resolution, diffusion-weighted imaging. Here, in a cross-sectional study of healthy adults across the lifespan (<i>n</i> = 140; ages 18-88 years; 72 females), we compared age-related differences in measures of white matter structural connectivity from standard (1.5 mm³ voxels; 3.375 µl volume) and high-resolution (1 mm³; 1 µl volume) diffusion-weighted imaging, 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 and functional (resting-state functional magnetic resonance imaging) connectivity using graph theory. Results revealed more pronounced age-related decreases in structural connectivity for sensorimotor, ventral attention, and sub-cortical networks for high-resolution than standard diffusion-weighted imaging. 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 diffusion-weighted imaging, but by a combination of high-resolution and standard diffusion-weighted imaging for between-network connectivity. Thus, relative to standard diffusion-weighted imaging, high-resolution diffusion-weighted imaging may better capture age-related differences in white matter connectivity and their constraint on age-related alterations in brain function and cognitive performance.