Altered structural connectivity in white matter lesion-induced mild cognitive impairment: a probabilistic fiber...

White matter lesions (WMLs) are a common cause of vascular cognitive impairment, yet the nature of whole-brain structural connectivity alterations in WML-related mild cognitive impairment (MCI) remains incompletely understood. In this study, an integrated approach combining whole-brain probabilistic fiber tracking with graph theory analysis was employed to investigate structural network changes in 33 patients with WML-related MCI and 37 healthy controls. The results revealed that, at the MCI stage, the brain's structural network exhibited not only reduced connectivity in specific neural circuits-primarily fronto-basal ganglia pathways-but also widespread increased connectivity, particularly between the frontal lobe and other cortical regions. Group comparisons identified 50 significantly altered connections (42 increased, 8 decreased), predominantly involving cortico-cortical, cortico-deep gray matter, and deep gray matter-deep gray matter pathways. Despite these connection-level abnormalities, no significant differences were observed in global or nodal graph-theoretical metrics. Notably, eight of the altered connections showed significant correlations with Montreal Cognitive Assessment (MoCA) scores. These structural alterations were closely associated with cognitive and behavioral deficits, indicating that they might serve as exploratory imaging indicators for WML-induced cognitive impairment.