Hyperconnectivity of Self-Referential Network as a Predictive Biomarker of the Progression of Alzheimer’s Disease

Article type: Research Article

Authors: Yao, Weina^a | Chen, Haifeng^{b; c; d} | Luo, Caimei^b | Sheng, Xiaoning^b | Zhao, Hui^{b; c; d} | Xu, Yun^{b; c; d} | Bai, Feng^{b; c; d; *} | Alzheimer’s Disease Neuroimaging Initiative¹

Affiliations: [a] Department of Neurology, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China | [b] Department of Neurology, Nanjing Drum Tower Hospital of The Affiliated Hospital of Nanjing University Medical School, and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing University, Nanjing, China | [c] Jiangsu Province Stroke Center for Diagnosis and Therapy, Nanjing, China | [d] Nanjing Neuropsychiatry Clinic Medical Center, Nanjing, China

Correspondence: [*] Correspondence to: Feng Bai, Department of Neurology, Nanjing Drum Tower Hospital of The Affiliated Hospital of Nanjing University Medical School, and The State Key Laboratory of Pharmaceutical Biotechnology, Institute of Brain Science, Nanjing Uni-versity, Nanjing 210008, China. E-mail: [email protected].

Note: [1] Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) data-base (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 the analysis or writing of this report. A complete listing of ADNI investigators can be fo-und at http://adni.loni.usc.edu/wp-content/uploads/how_to_apply/ADNI_Acknowledgement_List.pdf.

Abstract: Background:Self-referential processing is associated with the progression of Alzheimer’s disease (AD), and cerebrospinal fluid (CSF) proteins have become accepted biomarkers of AD. Objective:Our objective in this study was to focus on the relationships between the self-referential network (SRN) and CSF pathology in AD-spectrum patients. Methods:A total of 80 participants, including 20 cognitively normal, 20 early mild cognitive impairment (EMCI), 20 late MCI (LMCI), and 20 AD, were recruited for this study. Independent component analysis was used to explore the topological SRN patterns, and the abnormalities of this network were identified at different stages of AD. Finally, CSF pathological characteristics (i.e., CSF Aβ, t-tau, and p-tau) that affected the abnormalities of the SRN were further determined during the progression of AD. Results:Compared to cognitively normal subjects, AD-spectrum patients (i.e., EMCI, LMCI, and AD) showed a reversing trend toward an association between CSF pathological markers and the abnormal SRN occurring during the progression of AD. However, a certain disease state (i.e., the present LMCI) with a low concentration of CSF tau could evoke more hyperconnectivity of the SRN than other patients with progressively increasing concentrations of CSF tau (i.e., EMCI and AD), and this fluctuation of CSF tau was more sensitive to the hyperconnectivity of the SRN than the dynamic changes of CSF Aβ. Conclusion:The integrity of the SRN was closely associated with CSF pathological characteristics, and these findings support the view that the hyperconnectivity of the SRN will play an important role in monitoring the progression of the pre-dementia state to AD.

Keywords: Alzheimer’s disease spectrum patients, cerebrospinal fluid pathology, functional connectivity, hyperconnectivity, self-referential network

DOI: 10.3233/JAD-201376

Journal: Journal of Alzheimer's Disease, vol. 80, no. 2, pp. 577-590, 2021