DTI-ALPS alterations in cerebral small vessel disease: Associations with executive deficits and gait disorders via white matter injury

Cerebral small vessel disease (CSVD) is a major cause of executive dysfunction and gait disturbances in older adults, with white matter injury being a key contributor. Although white matter injury has been extensively studied, the upstream mechanisms that drive this injury remain unclear. This study aimed to investigate whether a lower diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, an indirect MRI marker related to perivascular diffusivity and putative glymphatic function, is associated with white matter injury and related functional impairments in CSVD. A total of 160 participants, including 43 healthy controls and 117 CSVD patients with varying disease burdens, underwent multimodal MRI, including diffusion tensor imaging (DTI) to assess white matter microstructure. The results revealed that a lower DTI-ALPS index was independently associated with poorer executive performance and slower gait speed. Voxel-wise analysis identified significant associations between DTI-ALPS and diffusion metrics in the fornix, a key white matter structure. The DTI-ALPS index provided incremental predictive value for gait impairment beyond traditional lesion markers such as white matter hyperintensity volume (WMHV). Furthermore, age significantly moderated the relationship between DTI-ALPS and gait, suggesting that these associations may be stronger in older individuals. These findings support the potential utility of DTI-ALPS as an imaging marker associated with functional decline in CSVD.