Abstract

Aims: The prevalence of white matter hyperintensities (WMH) rises dramatically with aging. Both the progression of WMH and default mode network (DMN) have been proven to be closely associated with cognitive function. Thus, we hypothesized that changes in functional connectivity (FC) and structural connectivity (SC) of the DMN contributed to WMH related cognitive impairment. Methods: A total of 116 subjects were enrolled from the Cerebral Small Vessel Disease Register in Drum Tower Hospital of Nanjing University, and were distributed across three categories according to Fazekas rating scale: WMH I(n=57), WMH II(n=34), and WMH III (n=25). The clinical and neuropsychological data were collected, and all participants underwent 3D T1 weighted images, T2 weighted images, 3D fluid attenuated inversion recovery (FLAIR) images, diffusion tensor images (DTI), and diffusion weighted imaging (DWI). The alterations of FC and SC within the DMN were further explored in these subjects. Results: The study found that age and hypertension were risk factors for WMH progression. Subjects with a larger WMH burden displayed higher DMN FC in the medial frontal gyrus (MFG), while lower DMN FC in the thalamus. After adjustment for age, gender, and education, the increasing FC between the MFG, posterior cingulate cortex (PCC), and ascending mean diffusivity (MD) of the white matter tracts between the hippocampus and PCC were independent indicators of worse performance in memory. Moreover, the decreasing FC between the thalamus, PCC, and ascending MD of the white matter tracts between the thalamus and PCC were independent risk factors for a slower processing speed. Conclusion: The changes in FC and SC within the DMN attributed to WMH progression were responsible for the cognitive impairment.

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