Neurovascular decoupling in cerebral small vessel disease-related gait disturbances in middle-aged and older adults: associations with blood biomarkers YKL-40 and neurofilament light chain

Cerebral small vessel disease (CSVD) is a leading cause of gait disturbances in older adults, potentially driven by neurovascular dysfunction and associated neurodegenerative processes; however, the specific mechanisms of gait disturbances have been under-researched. This study investigated neurovascular decoupling in CSVD-related gait disturbances and its association with blood biomarkers YKL-40 and neurofilament light chain (NFL). A total of 86 CSVD patients (47 with gait disorders, 39 without) and 40 healthy controls were enrolled in this study. Magnetic resonance imaging assessed regional cerebral blood flow (CBF) and functional connectivity. Gait parameters, cognitive function (Montreal cognitive assessment; trail making test, and Stroop color and word test), and blood YKL-40/NFL levels were also measured. An exploratory mediation model was developed in which the levels of blood YKL-40 and NFL, together with cognitive and psychological scale scores, were specified as latent mediating variables. Elevated blood levels of YKL-40 and NFL in CSVD patients with gait disorders (CSVD–GD) demonstrated strong diagnostic utility, with a combined predictor area under the curve (AUC) of 0.88, sensitivity of 85%, and specificity of 79%. CSVD–GD patients exhibited decreased CBF/functional connectivity ratios (CBF/DC) in the left superior frontal gyrus, thalamus, and hippocampus, which correlated with gait speed, executive function, and blood levels of YKL-40 and NFL. Mediation analysis revealed that scores on the attention–execution function scale in the left superior frontal gyrus and blood YKL-40 levels in the left thalamus partially mediated the impact of dual-tasking on gait performance. Neurovascular uncoupling may help to further elucidate gait dysfunction associated with CSVD, and blood levels of YKL-40 and NFL may serve as biomarkers for predicting gait impairment in CSVD.