Impaired Memory Awareness and Loss Integration in Self-Referential Network Across the Progression of Alzheimer’s Disease Spectrum

Article type: Research Article

Authors: Chen, Shanshan^{a; 1} | Song, Yu^{a; 1} | Xu, Wenwen^a | Hu, Guanjie^{b; c} | Ge, Honglin^{b; c} | Xue, Chen^d | Gao, Ju^e | Qi, Wenzhang^d | Lin, Xingjian^{a; *} | Chen, Jiu^{b; c; *} | the Alzheimer’s Disease Neuroimaging Initiative²

Affiliations: [a] Department of Neurology, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [b] Institute of Neuropsychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [c] Institute of Brain Functional Imaging, Nanjing Medical University, Nanjing, Jiangsu, China | [d] Department of Radiology, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China | [e] Department of Geriatric Psychiatry, the Affiliated Brain Hospital of Nanjing Medical University, Nanjing, Jiangsu, China

Correspondence: [*] Correspondence to: Xingjian Lin, Department of Neurology, the Affiliated Brain Hospital of Nanjing Medical University, No.264, Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210029, China. Tel.: +86 025 82296097; E-mail: [email protected] and Jiu Chen, Institute of Neuropsychiatry, Institute of Brain Functional Imaging, the Affiliated Brain Hospital of Nanjing Medical University, No.264, Guangzhou Road, Gulou District, Nanjing, Jiangsu, 210029, China. Tel.: +86 025 82296623; E-mails: [email protected]; [email protected].

Note: [1] These authors contributed equally to this work.

Note: [2] 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 the 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: Background:Anosognosia, or unawareness of memory deficits, is a common manifestation of Alzheimer’s disease (AD), but greatly variable in subjective cognitive decline (SCD) and amnestic mild cognitive impairment (aMCI) subjects. Self-referential network (SRN) is responsible for self-referential processing and considered to be related to AD progression. Objective:Our aim is to explore connectivity changes of SRN and its interaction with memory-related network and primary sensorimotor network (SMN) in the AD spectrum. Methods:About 444 Alzheimer’s Disease Neuroimaging Initiative subjects (86 cognitively normal [CN]; 156 SCD; 146 aMCI; 56 AD) were enrolled in our study. The independent component analysis (ICA) method was used to extract the SRN, SMN, and memory-related network from all subjects. The alteration of functional connectivity (FC) within SRN and its connectivity with memory-related network/SMN were compared among four groups and further correlation analysis between altered FC and memory awareness index as well as episodic memory score were performed. Results:Compared with CN group, individuals with SCD exhibited hyperconnectivity within SRN, while aMCI and AD patients showed hypoconnectivity. Furthermore, aMCI patients and AD patients both showed the interruption of the FC between the SRN and memory-related network compared to CN group. Pearson correlation analysis showed that disruptive FC within SRN and its interaction with memory-related network were related to memory awareness index and episodic memory scores. Conclusion:In conclusion, impaired memory awareness and episodic memory in the AD spectrum are correlated to the disconnection within SRN and its interaction with memory-related network.

Keywords: Alzheimer’s disease, amnestic mild cognitive impairment, anosognosia, memory awareness index, memory network, network interaction, self-referential network, subjective cognitive decline

DOI: 10.3233/JAD-210541

Journal: Journal of Alzheimer's Disease, vol. 83, no. 1, pp. 111-126, 2021