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.

Over the last several decades, significant progress has been made in the diagnostic criteria of Alzheimer’s disease (AD) to identify its early stages, including subjective cognitive decline and mild cognitive impairment. However, the previous research rarely took account of individual differences when evaluating AD-spectrum patients at different stages, thereby resulting in similar treatment, which was not only ineffective but also resulted in the missed window of opportunity for intervention. In this review, we propose the Brief Risk Rating Scale (BRRS), which is predominantly based on extant literature concerning AD risk factors and brain alterations, with the aim of providing a preliminary screening and monitoring tool that can facilitate the assessment of individual’s risk level, the prediction and tracking of disease progression, as well as precise treatment in a timely manner. Meanwhile, due to its simplicity and ease of use, it can be widely promoted and likewise accessible to clinicians in grassroots clinics. In general, the scale comprises two parts: The original score (O) related to patients’ risk factors and the variation score (V) related to brain abnormalities tested by different sequences of magnetic resonance imaging. In addition, the advantages along with its clinical application, such as introducing BRRS into cognitive training and brain stimulation, are also discussed. We conclude that BRRS positively contributes to enhancing the accuracy of clinical diagnosis and the efficiency of personalized treatment in AD-spectrum patients, with individual differences fully considered and little additional burden added. However, the weight coefficient of each item in BRRS should be thoroughly studied in future research.