Individual Proportion Loss of Functional Connectivity Strength: A Novel Individual Functional Connectivity Biomarker for Subjective Cognitive Decline Populations

Simple Summary Objective biomarkers for the diagnosis of subjective cognitive decline (SCD) are critical for intervention in the Alzheimer's disease (AD) disease process. Previous research has shown that functional magnetic resonance imaging (fMRI) is a significant tool for detecting abnormal interregional functional connectivity (FC) in SCD populations. However, traditional FC calculations do not reveal the high individual variation in the SCD population. We proposed a new framework for individual proportion loss of functional connectivity strength (IPLFCS) based on FC to identify SCD biomarkers, and further explore the relationship between biomarkers and amyloid deposition as well as neuropsychological performance. The study findings indicated that IPLFCS in the left middle temporal gyrus (LMTG) was identified as a potential biomarker that correlated with cortical amyloid deposition and cognitive performance. High individual variation in the subjective cognitive decline (SCD) population makes functional connectivity (FC) biomarkers unstable. This study proposed a novel individual FC index, named individual proportion loss of functional connectivity strength (IPLFCS), and explored potential biomarkers for SCD using this new index. We proposed an IPLFCS analysis framework and compared it with traditional FC in Chinese and Western cohorts. Post hoc tests were used to determine biomarkers. Pearson's correlation analysis was used to investigate the correlation between neuropsychological scores or cortical amyloid deposits and IPLFCS biomarkers. Receiver operating characteristic curves were utilized to evaluate the ability of potential biomarkers to distinguish between groups. IPLFCS of the left middle temporal gyrus (LMTG) was identified as a potential biomarker. The IPLFC was correlated with the traditional FC (r = 0.956, p < 0.001; r = 0.946, p < 0.001) and cortical amyloid deposition (r = -0.245, p = 0.029; r = -0.185, p = 0.048) in both cohorts. Furthermore, the IPLFCS decreased across the Alzheimer's disease (AD) continuum. Its diagnostic efficiency was superior to that of existing fMRI biomarkers. These findings suggest that IPLFCS of the LMTG could be a potential biomarker of SCD.