Gait speed and muscle mass as dual mediators in the link between white matter hyperintensities and Alzheimer's disease

Background Gait speed and muscle mass have been independently associated with both white matter hyperintensities (WMH) and Alzheimer's disease (AD), indicating complex interrelationships among these factors. Objective This study aims to investigate how gait speed and muscle mass function as mediators in the association between WMH and AD. Methods A total of 257 participants comprising 165 individuals with AD and 92 cognitively normal controls were included in this study. All participants underwent clinical evaluations, including volumetric brain magnetic resonance imaging and neuropsychological testing with the Korean version of CERAD Packet. WMH volume was calculated using automated segmentation analysis from 3D MRI images. Gait speed was measured using a timed 4-meter walk. Appendicular skeletal muscle mass (ASM) was measured using the bioelectrical impedance analysis. Results Multivariate logistic regression analysis revealed that slower gait speed (OR: 0.98, 95% CI: 0.95–0.998), lower ASM index (ASMI) (OR: 0.49, 95% CI: 0.26–0.93), and greater WMH volume (OR = 1.07; 95% CI: 1.01–1.14) were significantly associated with AD. Significant negative correlations were observed between gait speed and WMH volume (β = −0.32, p < 0.001), and between ASMI and WMH volume (β = −0.20, p = 0.022). Path analysis provided further clarification of the interrelationships, revealing that gait speed and ASMI emerged as significant mediators through their combined indirect effect (β = 0.20, 95% CI: 0.13–0.28) within the WMH-AD pathway. Conclusions Our findings demonstrate that both gait speed and muscle mass play crucial roles as dual mediators, negatively influencing the pathway connecting WMH to AD.