Synopsis

Cerebral small vessel disease(CSVD) is the most common cause of vascular cognitive impairment. Early diagnosis and intervention could prevent patients from progressing to dementia rapidly. DTI deterministic tractography and structural network analysis based on graph theory were utilized to explore the difference of structural connectome between CSVD patients and normal individuals. The results demonstrated the disruption of structural connection at global level and reduction of network efficiency at nodal level. Especially, the decrease of nodal efficiency in the right cuneus gyrus was associated with the mild memory loss in CSVD patients. Our results may provide crucial clues to therapeutic interventions.

Introduction

Method

Result

Global level: the brain network in two groups all demonstrated small world properties(γ≥1 and λ ≈ 1 or γ/λ>1)³, suggesting the tenet of most efficient connection has not been destroyed, but the difference of shortest path and cluster coefficient between two groups were not significant. CSVD group displayed significantly lower global efficiency and local efficiency compared with NC group(Figure 1).

Nodal level: Figure2,3 illustrated the brain regions with significant differences of nodal local efficiency between two groups. Compared to NC group, CSVD group showed lower nodal efficiency in 8 nodes including bilateral cuneus gyrus, superior occipital gyrus, left postcentral gyrus and right pre-cuneus gyrus ,lingual gyrus and superior parietal gyrus (p<0.05, FDR-corrected). No region was found different in betweenness centrality.

Clinical scales: MMSE, AVLT(S/L), TMT(A/B) and VFT scales were evaluated to quantify overall cognitive function, memory, execution and verbal frequency respectively, only VFT showed no difference between two groups, Moreover, the nodal efficiency of the right cuneus gyrus is positively correlated with AVLT(S/L) and MMSE scores in 37 patients, suggesting decreased nodal local efficiency of the right cuneus gyrus related to an impairment of episodic memory in patients with CSVD.(Figure4)

Discussion

In this study, both groups exhibited small-world characteristics but the difference didn’t differ. XF Xie et al. found patients with depressive symptoms in CSVD also showed small world properties⁴, as well as in infancy², which suggested that small world is an inherently property to keep brain in an efficient and tight connection.

CSVD group demonstrated lower efficiency at global level and also in eight brain regions, suggesting that the ability of information integration and separation was weakened in CSVD patients⁵, in line with the study of Andrew J⁶. Most of the regions were located around the intra-parietal sulcus and the frontal regions were spared, suggested that the higher-level cognitive occurred after posterior awareness arose⁷ has not been impaired, corresponding to the very mild cognitive impairment of the CSVD patients enrolled.

Betweenness centrality , defined as the fraction of all shortest paths that pass through the node⁸,representing the importance of a node’s functional capability in sending signals and passing information in the brain, showed no difference in all regions. However, Seo EH observed that the betweenness centrality was lower in patients with MCI and PD⁹. The discrepancy may be resulted by the heterogeneity of the patients, or may also suggested that the nodal efficiency a more sensitive index than betweenness centrality assessing the brain structural connectivity as Rubinov M⁸ reported.

Moreover, episodic memory assessed by AVLT(S/L) was positively correlated with the nodal efficiency changes of the right cuneus gyrus. The decline of nodal efficiency in cuneus gyrus may be caused by the fiber loss connecting to the dorsal frontal cortex¹⁰, due to WMH and lacunes which are two important characteristics of CSVD patients, and typically resulted episodic memory loss in those patients^{11, 12}.

Conclusion

Acknowledgements

References