Physical function moderates the relationship between white matter characteristics and gait variability during uneven terrain walking in aging, with free water being more strongly associated with baseline gait variability in lower-functioning than higher-functioning older adults, particularly in the body of corpus callosum.
Key Findings
Results
Lower-functioning older adults showed greater baseline gait variability and steeper increases in variability with increasing terrain unevenness compared to both young adults and higher-functioning older adults.
Participants included 22 young adults (22.45 ± 2.58 years) and 86 older adults (75.47 ± 6.77 years)
Older adults were classified as higher- or lower-functioning based on Short Physical Performance Battery (SPPB) scores
Walking behavior was quantified using step-duration coefficient of variation (COV) and perceived stability
Treadmill walking was assessed across flat, low, medium, and high uneven terrain conditions
Results
Older adults showed widespread higher free water (FW) and lower tissue integrity than young adults, particularly in frontal and motor-related white matter.
Primary white matter outcomes were free water (FW) and free water corrected fractional anisotropy (FAt)
Differences were particularly prominent in frontal and motor-related white matter regions
Both extracellular free water and tissue-specific measures were examined to distinguish between these white matter compartments
Diffusion-weighted MRI was used to quantify white matter microstructure
Results
Higher-functioning older adults had higher axial diffusivity (ADt) than lower-functioning older adults in frontal and interhemispheric regions.
This finding emerged from secondary analyses comparing the two older adult subgroups
Differences were localized to frontal and interhemispheric white matter regions
Axial diffusivity (ADt) was a free water-corrected tissue-specific measure
This finding suggests microstructural differences between physical function subgroups within the older adult population
Results
Higher free water was more strongly associated with greater baseline gait variability in lower-functioning than higher-functioning older adults, particularly in the body of the corpus callosum.
A significant group-by-behavior interaction was identified
The association between FW and gait variability was moderated by physical function group
The corpus callosum body was the primary region showing this differential association
This finding indicates that the neural correlates of gait variability differ depending on physical function status in older adults
Results
Extracellular free water and tissue-specific white matter measures showed distinct associations with baseline versus uneven-terrain walking in older adults.
Free water (FW) was more strongly linked to baseline gait variability
Tissue-specific measures showed distinct patterns of association with uneven-terrain walking behavior
This dissociation suggests that different white matter compartments may contribute differently to flat versus challenging walking conditions
The findings highlight the importance of using multi-compartment diffusion models (free water elimination) rather than standard DTI
Methods
The study examined age and physical function group differences in white matter microstructure and tested whether associations between white matter measures and uneven-terrain walking differed between groups.
Study used structural and diffusion-weighted MRI combined with treadmill walking assessment
Four terrain conditions were tested: flat, low, medium, and high uneven terrain
Sample comprised 22 young adults and 86 older adults
The free water elimination method was used to separately quantify extracellular free water (FW) and tissue-specific fractional anisotropy (FAt)
What This Means
This research suggests that the relationship between brain white matter health and walking ability on uneven surfaces is different depending on how physically fit an older adult is. The study compared young adults, higher-functioning older adults, and lower-functioning older adults (classified by a standard physical performance test) as they walked on a treadmill with varying degrees of surface unevenness. Lower-functioning older adults had the most variable and unstable gait, and their walking became more erratic as the terrain got rougher compared to both young adults and higher-functioning older adults. Brain imaging revealed that older adults in general had more 'free water' in their white matter—a marker of tissue deterioration—and lower structural integrity, especially in brain regions involved in movement planning and control.
A key finding was that the link between free water in the brain and walking variability was much stronger in lower-functioning older adults than in higher-functioning ones, and this relationship was especially prominent in a brain region called the corpus callosum, which connects the two hemispheres of the brain. This research suggests that poorer physical function amplifies the impact of white matter deterioration on gait stability, meaning that the same degree of brain change may have a larger effect on walking in people who are already less physically capable. Additionally, the study found that extracellular brain tissue changes and changes within the nerve fiber tissue itself were associated with different aspects of walking—baseline variability versus responses to challenging terrain—pointing to distinct neural mechanisms underlying these two aspects of gait.
These findings matter because falls on uneven terrain are a major cause of injury in older adults, and understanding which brain changes are most relevant to walking difficulty could help identify who is at greatest risk. This research suggests that assessing both brain white matter health and physical function together may provide a more complete picture of mobility decline in aging than either measure alone, and that interventions targeting both brain health and physical fitness could potentially have complementary benefits for maintaining safe walking ability in older adults.
Tasci S, Sato S, Salminen J, Prusty P, Shah V, Fettrow T, et al.. (2026). Physical function moderates the relationship between white matter characteristics and gait variability during uneven terrain walking in aging.. Neurobiology of aging. https://doi.org/10.1016/j.neurobiolaging.2026.08.004