Lower Myelin Content Is Associated With Lower Gait Speed in Cognitively Unimpaired Adults.

Mounting evidence indicates that abnormal gait speed predicts the progression of neurodegenerative diseases, including Alzheimer's disease. Understanding the relationship between white matter integrity, especially myelination, and motor function is crucial to the diagnosis and treatment of neurodegenerative diseases. We recruited 118 cognitively unimpaired adults across an extended age range of 22-94 years to examine associations between rapid or usual gait speeds and cerebral myelin content. Using our advanced multicomponent magnetic resonance relaxometry method, we measured myelin water fraction (MWF), a direct measure of myelin content, as well as longitudinal and transverse relaxation rates (R1 and R2), sensitive but nonspecific magnetic resonance imaging measures of myelin content. After adjusting for covariates and excluding 22 data sets due to cognitive impairments or artifacts, our results indicate that participants with higher rapid gait speed exhibited higher MWF, R1, and R2 values, that is, higher myelin content. These associations were statistically significant within several white matter brain regions, particularly the frontal and parietal lobes, splenium, anterior corona radiata, and superior fronto-occipital and longitudinal fasciculus. In contrast, we did not find any significant associations between usual gait speed and MWF, R1, or R2, which suggests that rapid gait speed may be a more sensitive marker of demyelination than usual gait speed. These findings advance our understanding on the implication of myelination in gait impairment among cognitively unimpaired adults, providing further evidence of the interconnection between white matter integrity and motor function.