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. 2019:24:102088.
doi: 10.1016/j.nicl.2019.102088. Epub 2019 Nov 12.

Disrupted functional and structural connectivity within default mode network contribute to WMH-related cognitive impairment

Xin Chen  1 , Lili Huang  1 , Qing Ye  1 , Dan Yang  1 , Ruomeng Qin  1 , Caimei Luo  1 , Mengchun Li  1 , Bing Zhang  2 , Yun Xu  3
Affiliations

Disrupted functional and structural connectivity within default mode network contribute to WMH-related cognitive impairment

Xin Chen et al. Neuroimage Clin. 2019.

Abstract

Aims: The prevalence of white matter hyperintensities (WMH) rises dramatically with aging. Both the progression of WMH and changing patterns of default mode network (DMN) have been proven to be closely associated with cognitive function. The present study hypothesized that changes in functional connectivity and structural connectivity of 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). All participants underwent neuropsychological tests and multimodal MRI scans, including diffusion tensor imaging and resting-state fMRI imaging. The alterations of functional connectivity and structural connectivity within the DMN were further explored.

Results: Age and hypertension were risk factors for WMH progression. Subjects with a higher WMH burden displayed higher DMN functional connectivity in the medial frontal gyrus, while lower DMN functional connectivity in the thalamus. After adjusting for aging, gender, and education, the increased DMN functional connectivity in the medial frontal gyrus, and the increased mean diffusivity of the white matter tracts between the hippocampus and posterior cingulate cortex were independent indicators of worse performance in memory. Moreover, the decreased DMN functional connectivity in the thalamus and increased mean diffusivity of the white matter tracts between the thalamus and posterior cingulate cortex were independent risk factors for a slower processing speed.

Conclusion: The changes in functional connectivity and structural connectivity within the DMN attributed to WMH progression were responsible for the development of cognitive impairment.

Keywords: Cognitive impairment; Default mode network; Functional connectivity; Structural connectivity; White matter hyperintensities.

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Conflict of interest statement

The authors declare no conflict of interest with respect to the research, authorship, and/or publication of this article.

Figures

Fig 1:
Fig. 1
Scatterplot showing the association of Fazekas scale scores and WMH volume [lg(ml)]. Fazekas scores were significantly correlated with WMH volume (r = 0.920, P<0.001). Abbreviations: WMH, white matter hyperintensities.
Fig 2:
Fig. 2
The group differences of FC. (A) The regions displayed significant difference among the three groups (Thalamus & Medial Frontal Gyrus). The result was corrected by Monte Carlo simulation with settings of voxel-wise P<0.01, FWHM = 6 mm, and cluster size>1215mm3. The scale was made up of correlation coefficients between PCC and brain regions within DMN and the 11 value in scale expressed the max correlation coefficients. (B) Subjects in the WMH III group displayed significantly greater FC in MFG than the other two groups. (C) Subjects in the WMH III group displayed significantly lower FC in thalamus than the other two groups. * P<0.05. Abbreviations: FC, functional connectivity; WMH, white matter hyperintensities; PCC, posterior cingulate cortex; DMN, default mode network; MFG, medial frontal gyrus.
Fig 3:
Fig. 3
Correlation analyses between cognitive function and FC in the WMH III group. (A) FC of PCC- MFG was negatively correlated with episodic memory [r ==−0.467, P = 0.029; 95% CI (−0.796, −0.034) ]. (B) FC of PCC-thalamus was positively correlated with language [r = 0.502, P = 0.017; 95% CI (0.084, 0.763)]. (C) FC of PCC-thalamus was negatively correlated with the time of processing speed [r ==−0.528, P = 0.012; 95% CI (−0.800, −0.167)]. (D) FC of PCC-thalamus was negatively correlated with the time of executive function [r ==−0.504, P = 0.017; 95% CI (−0.802, −0.178)]. The scores of each domain were z-transformed scores of the relevant tests. Correlation analyses were performed after adjustment of covariates (sex, age, and years of education). Abbreviations: FC, functional connectivity; WMH, white matter hyperintensities; PCC, posterior cingulate cortex; MFG, medial frontal gyrus; CI, confidence interval.
Fig 4:
Fig. 4
Comparison of FA or MD values across three groups. (A) The mean FA value of the PCC-hippocampus in the WMH III group was the lowest among the groups, even though it has not reached statistical significance. (B) The mean MD value of the PCC-hippocampus in the WMH III group was significantly higher than the former two groups. (C) The mean FA value of the PCC-thalamus was significantly lower than the former two groups. (D) The mean MD value of the PCC-thalamus was significantly higher than the former two groups. *: P<0.05. Abbreviations: FA, fractional anisotropy; MD, mean diffusivity; PCC, posterior cingulate cortex; WMH, white matter hyperintensities.
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