Abstract
BACKGROUND: White matter hyperintensity (WMH) is a common neuroimaging marker of cerebral small vessel disease (SVD) and a critical independent predictor of motor dysfunction, which increases the risk of disability, morbidity, and mortality. However, the mechanism underlying the relationship between WMH and motor function has not yet been fully clarified. It was hypothesized that cognitive impairment mediates the relationship between WMH and motor dysfunction in patients with SVD, which were considered predictor and outcome variables, respectively. METHODS: A total of 221 patients with SVD were enrolled in this study, and their magnetic resonance imaging (MRI), neuropsychological, and motor function data were collected. The MRI data were visually assessed to determine the WMH burden using the Fazekas scale. Cognition was evaluated using the Montreal Cognitive Assessment (MoCA). Motor function was assessed using the Tinetti Gait and Balance Scale and the Short Physical Performance Battery (SPPB). Finally, a bootstrap analysis was performed to determine whether cognition mediated the relationship between WMH and motor function. RESULTS: Of all the patients, 30.3% had mild WMH, 37.6% had moderate WMH, and 32.1% had severe WMH. Patients' cognition and motor function decreased as the WMH burden increased (P<0.01). The MoCA scores were associated with the Tinetti scale (r=0.545, P<0.01) and SPPB scores (r=0.365, P<0.01). Finally, multi-categorical mediation models confirmed our research hypothesis; the coefficients for the indirect effects had 95% confidence intervals (CIs) that excluded zero, indicating statistically significant mediation effects. CONCLUSIONS: WMH is associated with motor dysfunction, and this association is mediated by cognition in patients with SVD. This finding highlights the importance of early interventions targeting cognitive function to reduce the risk of motor dysfunction.