Aberrant default-mode functional connectivity in patients with end-stage renal disease: a resting-state functional MR imaging study.
OBJECTIVE
To investigate the functional connectivity of the default-mode network (DMN) in patients with end-stage renal disease (ESRD) by using independent component analysis of resting-state functional magnetic resonance (MR) imaging and to correlate these DMN connectivity changes with neuropsychological test results and clinical biomarkers.


METHODS
Medical research ethics committee approval and written informed consent were obtained. Forty-six patients with ESRD, including 22 with minimal nephrotic encephalopathy (MNE) and 24 without nephrotic encephalopathy, and 23 healthy control subjects underwent resting-state functional MR imaging. All patients were asymptomatic and without history of neurologic or psychiatric disease. Independent component analysis was used to isolate the DMN. To display the voxels that contributed most strongly to an independent component, the intensity values in each spatial map were converted to z scores, which indirectly provided a measurement of functional connectivity in the DMN. Maps of the DMN were compared among the groups. Pearson correlation analysis was performed to correlate abnormal DMN functional connectivity with serum urea, creatinine, duration of dialysis, duration of disease, and neuropsychological test scores.


RESULTS
Patients with ESRD showed significantly less functional connectivity in the posterior cingulate cortex, precuneus, and medial prefrontal cortex (MPFC) (P < .01) than did control subjects. Comparison of the two patient groups showed significantly reduced functional connectivity in the superior and MPFC in the MNE group (P < .01). The functional connectivity of the MPFC was positively correlated with digital symbol test score (R = 0.293, P = .048). Serum creatinine level was negatively correlated with functional connectivity of the posterior cingulate cortex and precuneus in patients with ESRD (R = -0.51, P = .002).


CONCLUSIONS
Functional connectivity in the DMN was impaired in patients with ESRD, with further reduction in the MPFC with the development of MNE, which might explain the reduced performance of these patients on neurocognitive tests. Serum creatinine level might be associated with impairment of the DMN in patients with ESRD.
From the Departments of Medical Imaging (L.N., L.J.Z., R.Q., Q.X., X.L., G.Z., G.M.L.) and Nephrology (J.W.), Jinling Hospital, Medical School of Nanjing University, 305 Zhongshan East Road, Xuanwu District, Nanjing, Jiangsu Province 210002, China;Department of Imaging Sciences, University of Rochester School of Medicine and Dentistry, Rochester, NY (T.Z.); and Department of Biomedical Engineering, Zhejiang University, Hangzhou, China (J.Z.).
Ling
L
Ni
Jiqiu
J
Wen
Long Jiang
LJ
Zhang
Tong
T
Zhu
Rongfeng
R
Qi
Qiang
Q
Xu
Xue
X
Liang
Jianhui
J
Zhong
Gang
G
Zheng
Guang Ming
GM
Lu
D000328:Adult; D001927:Brain Diseases / Q000503:physiopathology*; D001931:Brain Mapping / Q000379:methods; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D007676:Kidney Failure, Chronic / Q000503:physiopathology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009483:Neuropsychological Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D012146:Rest