Self-reference Network-Related Interactions During the Process of Cognitive Impairment in the Early Stages of Alzheimer’s Disease

Background: Normal establishment of cognition occurs after forming a sensation to stimuli from internal or external cues, in which self-reference processing may be partially involved. However, self-reference processing has been less studied in the Alzheimer’s disease (AD) field within the self-reference network (SRN) and has instead been investigated within the default-mode network (DMN). Differences between these networks have been proven in the last decade, while ultra-early diagnoses have increased. Therefore, investigation of the altered pattern of SRN is significantly important, especially in the early stages of AD. Methods: A total of 65 individuals, including 43 with mild cognitive impairment (MCI) and 22 cognitively normal individuals, participated in this study. The SRN, dorsal attention network (DAN), and salience network (SN) were constructed with resting-state functional magnetic resonance imaging (fMRI), and voxel-based analysis of variance (ANOVA) was used to explore significant regions of network interactions. Finally, the correlation between the network interactions and clinical characteristics was analyzed. Results: We discovered four interactions among the three networks, with the SRN showing different distributions in the left and right hemispheres from the DAN and SN and modulated interactions between them. Group differences in the interactions that were impaired in MCI patients indicated that the degree of damage was most severe in the SRN, least severe in the SN, and intermediate in the DAN. The two SRN-related interactions showed positive effects on the executive and memory performances of MCI patients with no overlap with the clinical assessments performed in this study. Conclusion: This study is the first and primary evidence of SRN interactions related to MCI patients’ functional performance. The influence of the SRN in the ultra-early stages of AD is nonnegligible. There are still many unknowns regarding the contribution of the SRN in AD progression, and we strongly recommend future research in this area.