Cerebral and blood correlates of reduced functional connectivity in mild cognitive impairment

Growing evidence suggests that decreased functional connectivity in cortical networks precedes clinical stages of Alzheimer's disease (AD), although our knowledge about cerebral and biological correlates of this phenomenon is limited. To shed light on this issue, we have investigated whether resting-state oscillatory connectivity patterns in healthy older (HO) and amnestic mild cognitive impairment (aMCI) subjects are related to anatomical grey matter (GM) and functional (2-[18F]fluoro-2-deoxy-D-glucose (FDG)-PET) changes of neuroelectric sources of alpha rhythms, and/or to changes in plasma amyloid-beta (Aβ) and serum lipid levels, blood markers tied to AD pathogenesis and aging-related cognitive decline. We found that aMCI subjects showed decreased levels of cortical connectivity, reduced FDG-PET intake of the precuneus, and GM atrophy of the thalamus, together with higher levels of Aβ and apolipoprotein B (ApoB) compared to HO. Interestingly, levels of high-density lipoprotein (HDL) cholesterol were positively correlated with the strength of neural-phase coupling in aMCI subjects, and increased triglycerides accompanied bilateral GM loss in the precuneus of aMCI subjects. Together, these findings provide peripheral blood correlates of reduced resting-state cortical connectivity in aMCI, supported by anatomo-functional changes in cerebral sources of alpha rhythms. This framework constitutes an integrated approach to assess functional changes in cortical networks through neuroimaging and peripheral blood markers during early stages of neurodegeneration.