Altered static and dynamic functional network connectivity related to cognitive decline in individuals with white matter hyperintensities

Abstract

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.