## 5 Discussion  
In this study, we found that the IPLFCS could detect more SCD-related areas than traditional FC. Thus, the IPLFCS of the LMTG may be a potential biomarker of SCD. Notably, we employed methodological optimization to ensure the robustness of our results. First, we performed multiple permutation tests on data from the two cohorts. These measures reinforce the power of the results. We further demonstrated that the IPLFCS of the LMTG presented a gradually deteriorating trend in the three groups of SCD, MCI and AD. It also showed significant correlations with amyloid deposition and cognitive performance. Therefore, the IPLFCS of the LMTG is likely to be a better indicator for the inclusion of SCD, which might increase the monitoring capabilities via objective biomarkers and decrease the errors of subjective descriptions to a certain extent. Monitoring SCD can help researchers understand the occurrence and progression of SCD, promoting knowledge and treatment of this disease. Currently, potential biomarkers of the preclinical AD spectrum using different neuroimaging modalities have been explored [39; 40; 41; 42]. We noted that the diagnostic efficiency of the functional features of MRI was superior to that of the structural or metabolic modalities, indicating that it could be a sensitive and powerful biomarker for SCD [10; 11]. The IPLFCS is a novel FC metric that standardizes the connectivity strength of the baseline and better addresses the issue of high noise in fMRI compared to FC. Our results showed that IPLFCS could identify more differential brain regions in SCD populations than the conventional  
Figure 5: The results of ROC analysis among IPLFCS, ALFF, ReHo and FC. (**a**) The ROC results of NC1 vs. SCD1. (**b**) The ROC results of NC1 vs. MCI1. (**c**) The ROC results of NC1 vs. AD1. (**d**) The ROC results of NC2 vs. SCD2. (**e**) The ROC results of NC2 vs. MCI2. (**f**) The ROC results of NC2 vs. AD2. FC. Therefore, we further performed the individually specified IPLFCS to characterize the quantitative decrease degree. The IPLFCS of the LMTG was found to have a robust diagnostic efficacy, with accuracy rates of 80% and 76% in categorizing SCD from NC in the different cohorts, respectively. Our result of a single modality also obtained a good classification performance similar to that of the multimodal analysis, which will contribute to reducing the medical cost of patients. Evidence indicated that the IPLFCS of the LMTG exhibited increased diagnostic specificity for SCD in practical applications. As individuals age and experience memory deficits, a reduction in FC is evident and is linked to factors such as the massive loss of neurons and synapses during the development of aging and AD [43]. However, conventional neuroimaging biomarkers are difficult to distinguish due to subtle reductions in connection strength in the early stages of SCD [44; 45]. Therefore, the establishment of reliable and sensitive markers for early diagnosis and monitoring of brain connectivity remains an important challenge. In this study, significant differences in IPLFCS were discovered between the independent NC and SCD groups. Additionally, the IPLFCS of the LMTG progressively decreased across the AD continuum. Correlation analysis demonstrated that the IPLFCS in this region was related to cognitive scores. These results suggest that functional loss of the LMTG occurs as early as the SCD stage, with progressive progression of the IPLFCS and concomitant cognitive decline. The LMTG is a crucial region in the processing of memory [46; 47; 48]. It has FC to the hippocampus as well as different parcellations in the frontal and parietal. It is responsible for rapid encoding of new associations and memory consolidation [49; 50]. An fMRI study reported that the LMTG is involved in sublexical processing of Chinese character recognition [51].