Classification of type 2 diabetes mellitus with or without cognitive impairment from healthy controls using high-order functional connectivity

Yuna Chen, Zhen Zhou, Yi Liang, Xin Tan, Yifan Li, Chunhong Qin, Yue Feng, Xiaomeng Ma, Zhanhao Mo, Jing Xia, Han Zhang, Shijun Qiu, Dinggang Shen

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)


Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment and may progress to dementia. However, the brain functional mechanism of T2DM-related dementia is still less understood. Recent resting-state functional magnetic resonance imaging functional connectivity (FC) studies have proved its potential value in the study of T2DM with cognitive impairment (T2DM-CI). However, they mainly used a mass-univariate statistical analysis that was not suitable to reveal the altered FC “pattern” in T2DM-CI, due to lower sensitivity. In this study, we proposed to use high-order FC to reveal the abnormal connectomics pattern in T2DM-CI with a multivariate, machine learning-based strategy. We also investigated whether such patterns were different between T2DM-CI and T2DM without cognitive impairment (T2DM-noCI) to better understand T2DM-induced cognitive impairment, on 23 T2DM-CI and 27 T2DM-noCI patients, as well as 50 healthy controls (HCs). We first built the large-scale high-order brain networks based on temporal synchronization of the dynamic FC time series among multiple brain region pairs and then used this information to classify the T2DM-CI (as well as T2DM-noCI) from the matched HC based on support vector machine. Our model achieved an accuracy of 79.17% in T2DM-CI versus HC differentiation, but only 59.62% in T2DM-noCI versus HC classification. We found abnormal high-order FC patterns in T2DM-CI compared to HC, which was different from that in T2DM-noCI. Our study indicates that there could be widespread connectivity alterations underlying the T2DM-induced cognitive impairment. The results help to better understand the changes in the central neural system due to T2DM.

Original languageEnglish
Pages (from-to)4671-4684
Number of pages14
JournalHuman Brain Mapping
Issue number14
Publication statusPublished - 2021 Oct 1

Bibliographical note

Publisher Copyright:
© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.


  • cognitive impairment
  • dynamic functional connectivity
  • machine learning
  • resting-state brain networks
  • type 2 diabetes mellitus

ASJC Scopus subject areas

  • Anatomy
  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging
  • Neurology
  • Clinical Neurology


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