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White matter hyperintensities (WMH) are widely observed in older adults and are closely associated with cognitive impairment. However, the underlying neuroimaging mechanisms of WMH-related cognitive dysfunction remain unknown. This study recruited 61 WMH individuals with mild cognitive impairment (WMH-MCI, n = 61), 48 WMH individuals with normal cognition (WMH-NC, n = 48) and 57 healthy control (HC, n = 57) in the final analyses. We constructed morphological networks by applying the Kullback-Leibler divergence to estimate interregional similarity in the distributions of regional gray matter volume. Based on morphological networks, graph theory was applied to explore topological properties, and their relationship to WMH-related cognitive impairment was assessed. There were no differences in small-worldness, global efficiency and local efficiency. The nodal local efficiency, degree centrality and betweenness centrality were altered mainly in the limbic network (LN) and default mode network (DMN). The rich-club analysis revealed that WMH-MCI subjects showed lower average strength of the feeder and local connections than HC (feeder connections: P = 0.034; local connections: P = 0.042). Altered morphological connectivity mediated the relationship between WMH and cognition, including language (total indirect effect: −0.010; 95 % CI: −0.024, −0.002) and executive (total indirect effect: −0.010; 95 % CI: −0.028, −0.002) function. The altered topological organization of morphological networks was mainly located in the DMN and LN and was associated with WMH-related cognitive impairment. The rich-club connection was relatively preserved, while the feeder and local connections declined. The results suggest that single-subject morphological networks may capture neurological dysfunction due to WMH and could be applied to the early imaging diagnostic protocol for WMH-related cognitive impairment. • The altered topological organization of morphological networks was mainly located in the DMN and LN. • The altered morphological connectivity mediated WMH-related cognitive impairment. • The rich-club connection was relatively preserved to delay cognitive decline. [ABSTRACT FROM AUTHOR]

White matter hyperintensities (WMH) of assumed vascular origin are common in elderly individuals and are closely associated with cognitive decline. However, the underlying neural mechanisms of WMH-related cognitive impairment remain unclear. After strict screening, 59 healthy controls (HC, n = 59), 51 patients with WMH and normal cognition (WMH-NC, n = 51) and 68 patients with WMH and mild cognitive impairment (WMH-MCI, n = 68) were included in the final analyses. All individuals underwent multimodal magnetic resonance imaging (MRI) and cognitive evaluations. We investigated the neural mechanism underlying WMH-related cognitive impairment based on static and dynamic functional network connectivity (sFNC and dFNC) approaches. Finally, the support vector machine (SVM) method was performed to identify WMH-MCI individuals. The sFNC analysis indicated that functional connectivity within the visual network (VN) could mediate the impairment of information processing speed related to WMH (indirect effect: 0.24; 95% CI: 0.03, 0.88 and indirect effect: 0.05; 95% CI: 0.001, 0.14). WMH may regulate the dFNC between the higher-order cognitive network and other networks and enhance the dynamic variability between the left frontoparietal network (lFPN) and the VN to compensate for the decline in high-level cognitive functions. The SVM model achieved good prediction ability for WMH-MCI patients based on the above characteristic connectivity patterns. Our findings shed light on the dynamic regulation of brain network resources to maintain cognitive processing in individuals with WMH. Crucially, dynamic reorganization of brain networks could be regarded as a potential neuroimaging biomarker for identifying WMH-related cognitive impairment. [ABSTRACT FROM AUTHOR]