Association of Functional and White Matter Structural Brain Network in Older Cerebral Small Vessel Disease With...

To investigate topological brain network properties, intra- and inter-network network patterns, rich-club organization, structural-functional coupling, and their associations with cognitive impairment in elderly patients with cerebral small vessel disease (CSVD).

A total of 264 participants were enrolled: 60 healthy controls, 93 CSVD patients without mild cognitive impairment (CSVD-NMCI), and 111 CSVD patients with MCI (CSVD-MCI). All underwent neuropsychological testing and multimodal magnetic resonance imaging (MRI). Structural and functional networks were constructed, and graph theory was applied to assess global and local topology. Associations among network metrics, default mode network (DMN), frontoparietal control network (FPCN), dorsal attention network (DAN), rich-club connectivity, structural connectivity (SC)-functional connectivity (FC) coupling, and cognitive scores were examined.

CSVD patients exhibited significant global and nodal topological disruption (p < 0.05, Bonferroni correction). In CSVD-MCI, FC was reduced within the DMN and DAN but increased within the FPCN. FC within the DAN and between DMN-DAN was positively correlated with Auditory Verbal Learning Test (AVLT) performance. SC-FC coupling was significantly higher in CSVD-MCI than in CSVD-NMCI and controls (p < 0.05). Rich-club, feeder, and local connections were markedly impaired in CSVD-MCI and correlated with AVLT and Symbol Digit Modalities Test scores.

CSVD is associated with decreased network efficiency and elevated SC-FC coupling. Altered FC in the FPCN, DMN, and DAN may indicate compensatory mechanisms, whereas rich-club disruption may be key evidence for cognitive impairment. These findings provide novel insights into network dysfunction underlying cognitive decline in CSVD.