Impaired white matter functional networks topology changed with white matter hyperintensities burden and relationship to cognition.

We aimed to investigate the topology alterations of white matter functional networks (WMFNs) associated with varying white matter hyperintensities (WMH) burden, and assess the relationship between topological changes of WMFNs and cognitive function in the individuals with moderate to severe WMH (m/sWMH). Fifty-four cognitively unimpaired individuals were enrolled and stratified into two groups: 26 with m/sWMH and 28 with mild WMH (mWMH). We used graph theory analysis to investigate the global and nodal topological alteration between two groups and to examine the association between WMFNs topological alterations and cognition. The results demonstrated that, compared to the mWMH group, the m/sWMH group exhibited alterations of global and nodal properties, including decreased clustering coefficient (Cp) and shortest path length (Lp), decreased nodal clustering coefficient (Ncp), increased nodal efficiency (Ne), as well as mixed increases and decreases in nodal degree centrality (Dc) and betweenness centrality (Bc). These alterations mainly occurred in the body of corpus callosum, left sagittal stratum (SS) (including the inferior longitudinal fasciculus and inferior fronto-occipital fasciculus, ILF and IFOF), the anterior limb of the internal capsule, cingulate gyrus, and inferior longitudinal fasciculus. The Pearson correlation analysis revealed that nodal properties (Ncp and Dc) in SS (including ILF and IFOF) were associated with cognitive scores in the m/sWMH group. Increased WMH burden may lead to the disintegration of WMFNs topology, which was closely associated with cognitive dysfunction (global cognitive function, attention and processing speed). The SS may be a biomarker for cognitive impairment in individuals with m/sWMH.