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Deteriorated functional and structural brain networks and normally appearing functional–structural coupling in diabetic kidney disease: a graph theory-based magnetic resonance imaging study

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Abstract

Purpose

This study was conducted in order to investigate the topological organization of functional and structural brain networks in diabetic kidney disease (DKD) and its potential clinical relevance.

Methods

Two hundred two subjects (62 DKD patients, 60 diabetes mellitus [DM] patients, and 80 healthy controls) underwent laboratory examination, neuropsychological test, and magnetic resonance imaging (MRI). Large-scale functional and structural brain networks were constructed and graph theoretical network analyses were performed. The effect of renal function on brain functional and structural networks in DKD patients was further evaluated. Correlations were performed between network properties and neuropsychological scores and clinical variables.

Results

Progressing deteriorated global and local network topology organizations (especially for functional network) were observed for DKD patients compared with control subjects (all p < 0.05, Bonferroni-corrected), with intermediate values for the patients with DM. DKD patients showed normally appearing functional–structural coupling compared with controls, while DM patients manifested functional–structural decoupling (p < 0.05, Bonferroni-corrected). Impaired kidney function markedly affected functional and structural network organization in DKD patients (all p < 0.05). Urea nitrogen correlated with global and local efficiency in the structural networks (r = − 0.551, p < 0.001; r = − 0.476, p < 0.001, respectively). Global and local efficiency in the structural networks and normalized characteristic path length in the functional networks were associated with information processing speed and/or psychomotor speed.

Conclusion

DKD patients showed enhanced functional and structural brain network disruption and normally appearing functional–structural coupling compared with DM patients, which correlated with kidney function, renal toxins, and cognitive performance.

Key Points

• DKD patients showed markedly disrupted functional and structural brain network efficiency measures compared with DM patients and healthy controls.

• Reduced kidney function clearly deteriorated functional and structural brain networks in DKD patients.

• DKD patients displayed normally appearing functional–structural coupling compared with DM patients.

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Abbreviations

γ :

Normalized clustering coefficient

λ :

Normalized characteristic path length

σ :

Small-worldness

AAL:

Automated anatomical labeling

ADA:

American Diabetes Association

ANCOVA:

Analysis of covariance

BUN:

Blood urea nitrogen

Cp:

Clustering coefficient

Cyst C:

Cystatin C

DKD:

Diabetic kidney disease

DM:

Diabetes mellitus

DPARSF:

Data Processing Assistant for Resting-State fMRI

DS:

Deep subcortical

DTI:

Diffusion tensor imaging

Eg:

Global efficiency

eGFR:

Estimated glomerular filtration rate

Eloc:

Local efficiency

FBG:

Fasting blood glucose

HbA1c:

Hemoglobin A1c

HDL-C:

High-density lipoprotein cholesterol

LDL-C:

Low-density lipoprotein cholesterol

Lp:

Characteristic path length

LTT:

Line Tracing Test

MMSE:

Mini-Mental State Examination

MoCA:

Montreal Cognitive Assessment

MRI:

Magnetic resonance imaging

NCT-A:

Number Connection Test type-A

PV:

Periventricular

rs-fMRI:

Resting-state functional magnetic resonance imaging

SAS:

Self-Rating Anxiety Scale

Scr:

Serum creatinine

SDS:

Self-Rating Depression Scale

SDT:

Serial Dotting Test

TC:

Total cholesterol

TIV:

Total intracranial volume

Tri:

Triglycerides

UA:

Uric acid

WML:

White matter lesions

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Funding

This study was funded by grants from the National Natural Science Foundation of China (81322020, 81230032, 81471644).

Author information

Author notes

  1. Drs. Yun Fei Wang, Ping Gu had equal contributions to this work.

Authors and Affiliations

  1. Department of Medical Imaging, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, Jiangsu, China

    Yun Fei Wang, Rongfeng Qi, Gang Zheng, Qiang Xu, Ya Liu, Guang Ming Lu & Long Jiang Zhang

  2. Department of Endocrinology, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China

    Ping Gu

  3. National Clinical Research Center of Kidney Disease, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, China

    Jiong Zhang

  4. Monash Biomedical Imaging, Monash University, Clayton, VIC, 3168, Australia

    Michael de Veer & Gang Zheng

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  1. Yun Fei Wang
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Corresponding author

Correspondence to Long Jiang Zhang.

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The scientific guarantor of this publication is Long Jiang Zhang.

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The authors declare that they have no conflicts of interest.

Statistics and biometry

No complex statistical methods were necessary for this paper.

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Written informed consent was obtained from all subjects (patients) in this study.

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Institutional Review Board approval was obtained.

Study subjects or cohorts overlap

Some study subjects or cohorts have not been previously reported.

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• prospective

• observational

• performed at one institution

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Wang, Y.F., Gu, P., Zhang, J. et al. Deteriorated functional and structural brain networks and normally appearing functional–structural coupling in diabetic kidney disease: a graph theory-based magnetic resonance imaging study. Eur Radiol 29, 5577–5589 (2019). https://doi.org/10.1007/s00330-019-06164-1

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