Background: While cerebral beta-amyloid accumulation was found in many studies to alter precuneus-based functional connectivity (FC) in mild cognitive impairment and demented Alzheimer’s disease (AD) patients, its impact is less well understood in subjective cognitive decline (SCD), which in the presence of underlying AD pathologic change corresponds to a progression to stage 2 of the clinical Alzheimer’s continuum in the 2018 National Institute on Aging and Alzheimer’s Association research framework, and represents the earliest clinical manifestation of AD.
Methods: From the DELCODE (DZNE – Longitudinal Cognitive Impairment and Dementia Study) cohort, two groups of 24 age- and gender-matched amyloid-positive SCD (SCDAβ+) and amyloid-negative SCD (SCDAβ-) patients were selected according to visual [18F]-Florbetaben PET readings, and studied with resting-state BOLD fMRI. Local (regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF)) and global (degree centrality (DC), precuneus seed-based FC maps) measures were calculated and compared between both groups. Furthermore, follow-up correlation analyses probed linear relationships of observed group differences with global as well as precuneal amyloid load measured by Florbetaben standard uptake value ratios (SUVRFBB).
Results: For the local measures, ReHo was significantly higher in the bilateral precuneus for the SCDAβ+ group, whereas ALFF and fALFF measures were not altered between groups. For the global measures, relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in the SCDAβ+ group. Moreover, the FC differences between precuneus and occipital areas were positively correlated with global (SCDAβ+) and local precuneus SUVRFBB (both groups).
Conclusions: While confounding influences due to a higher ratio of APOE e4 carriers in the SCDAβ+ group cannot be excluded, results indicate functional alterations in the precuneus hub region that were linearly related to beta-amyloid load, highlighting incipient pathology and possible compensatory mechanisms in stage 2 of the AD continuum.