Abnormal Brain Network Connectivity in a Triple-Network Model of Alzheimer’s Disease

Article type: Research Article

Authors: Li, Chenxi^{a; b} | Li, Youjun^{a; b} | Zheng, Liang^{a; b} | Zhu, Xiaoqi^{a; b} | Shao, Bixin^{a; b} | Fan, Geng^{a; b} | Liu, Tian^{a; b; *} | Wang, Jue^{a; b; *} | and Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] The Key Laboratory of Biomedical Information Engineering of Ministry of Education, The Key Laboratory of Neuro-informatics and Rehabilitation Engineering of Ministry of Civil Affairs, and Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, P.R. China | [b] National Engineering Research Center of Health Care and Medical Devices, Xi’an, P.R. China

Correspondence: [*] Correspondence to: Dr. Tian Liu and Dr. Jue Wang, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Biomedical Engineering, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an 710049, China. E-mail: [email protected] (J. Wang); [email protected] (T. Liu).

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (http://adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf

Abstract: Resting-state fMRI studies have demonstrated that Alzheimer’s disease (AD) is associated with aberrant organization and function of large-scale brain networks. However, the nature of the disruption of cross-network interactions in the key neurocognitive networks in the brain remains unclear. In this paper, we examined the ‘triple-network model’, including the default mode network (DMN), salience network (SN), and central executive network (CEN), to identify the cross-network interactions in late mild cognitive impairment (LMCI) and AD. With resting-state fMRI, we tested cross-network functional connectivity among the DMN, SN, and CEN in 33 AD patients, 24 LMCI, and 25 well-matched normal control subjects. Then, we identified the most influential brain regions affected by AD and LMCI. Finally, we investigated the relationship between aberrant functional connectivity and clinical cognitive dysfunction. We found the cross-network functional connectivity of the SN-centered ‘triple-network model’ was significantly impaired in the AD group and the alterations were negatively correlated with the Mini-Mental State Examination (MMSE) scores. For the LMCI group, the functional connectivity of the SN-centered ‘triple-network model’ also changed compared to AD; however, we found no correlation with MMSE score. As predicted, the abnormal connections among the three networks mainly overlap with the key nodes of the three networks. Overall, our findings suggested that the interactions of the SN-centered ‘triple-network model’ are impaired in AD patients and that these alterations contribute to the decline in cognitive function. This ‘triple-network model’ provides new insights into AD and provides more information about the dysregulation of brain networks in AD.

Keywords: Alzheimer’s disease, functional brain network, late mild cognitive impairment, resting-state functional MRI, triple-network model

DOI: 10.3233/JAD-181097

Journal: Journal of Alzheimer's Disease, vol. 69, no. 1, pp. 237-252, 2019