Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status

Background: Amyloid-beta accumulation was found to alter precuneus-based functional connectivity (FC) in mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia, but its impact is less clear in subjective cognitive decline (SCD), which in combination with AD pathologic change is theorized to correspond to stage 2 of the Alzheimer's continuum in the 2018 NIA-AA research framework. Objective: This study addresses how amyloid pathology relates to resting-state fMRI FC in SCD, especially focusing on the precuneus. Methods: From the DELCODE cohort, two groups of 24 age- and gender-matched amyloid-positive (SCDA beta+) and amyloidnegative SCD (SCDA beta-) patients were selected according to visual [18F]-Florbetaben (FBB) PET readings, and studied with resting-state fMRI. Local (regional homogeneity [ReHo], fractional amplitude of low-frequency fluctuations [fALFF]) and global (degree centrality [DC], precuneus seed-based FC) measures were compared between groups. Follow-up correlation analyses probed relationships of group differences with global and precuneal amyloid load, as measured by FBB standard uptake value ratios (SUVRFBB). Results: ReHo was significantly higher (voxel-wise p < 0.01, cluster-level p < 0.05) in the bilateral precuneus for SCDA beta+ patients, whereas fALFF was not altered between groups. Relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in SCDA beta+ patients. In this latter cluster, precuneus-occipital FC correlated positively with global (SCDA beta+) and precuneus SUVRFBB (both groups). Conclusion: While partial confounding influences due to a higher APOE epsilon 4 carrier ratio among SCDA beta+ patients cannot be excluded, exploratory results indicate functional alterations in the precuneus hub region that were related to amyloid-beta load, highlighting incipient pathology in stage 2 of the AD continuum.