Physical function moderates the relationship between white matter characteristics and gait variability during uneven terrain walking in aging.

Navigating uneven terrain poses a significant challenge for older adults, often resulting in falls. Identifying the neural correlates of walking on uneven terrain might help understand the mechanisms of age-related mobility decline. We examined age and physical function group differences in white matter microstructure and tested whether associations between white matter measures and uneven-terrain walking behavior differed between these groups. Twenty-two young adults (22.45 ± 2.58 years) and 86 older adults (75.47 ± 6.77 years) completed structural and diffusion-weighted MRI and treadmill walking across flat, low, medium, and high uneven terrain conditions. Older adults were classified as higher- or lower-functioning based on Short Physical Performance Battery scores. Free water (FW) and free water corrected fractional anisotropy (FAt) were primary outcomes. Walking behavior was quantified using step-duration coefficient of variation (COV) and perceived stability. Lower-functioning older adults showed greater baseline gait variability and steeper increases in variability with increasing terrain unevenness than both young adults and higher-functioning older adults. Older adults showed widespread higher FW and lower tissue integrity than young adults, particularly in frontal and motor-related white matter. Secondary analyses showed that higher-functioning older adults had higher axial diffusivity (ADt) than lower-functioning older adults in frontal and interhemispheric regions. A significant group-by-behavior interaction showed that higher FW was more strongly associated with greater baseline gait variability in lower-functioning than higher-functioning older adults, particularly in the body of corpus callosum. Extracellular free water and tissue-specific white matter measures showed distinct associations with baseline versus uneven-terrain walking in older adults.