Decoupling of inter-regional functional connectivity and regional neural activity in Alzheimer Disease

Alzheimers disease (AD) and mild cognitive impairment (MCI) are characterized by aberrant regional neural activity and disrupted inter-regional functional connectivity (FC). It is, however, poorly understood how changes in regional neural activity and inter-regional FC interact in AD and MCI. Here, we investigated the link between regional neural activity and nodal topological measures of FC through simultaneous PET/MR measurement in 20 patients with MCI, 33 patients with AD, and 26 healthy individuals. First, we assessed regional glucose metabolism identified through FDG-PET (rFDG) (as a proxy of regional neural activity), and regional FC topology through clustering coefficient (CC) and degree centrality (DC) (as surrogates of local segregation and global connectivity, respectively). Next, we examined the potential moderating effect of disease status (AD or MCI) on the link between rFDG and FC topology using hierarchical moderated multiple regression analysis. Alterations in rFDG, CC, and DC were widespread in patients, and AD alters physiological coupling between regional metabolism and functional connectivity particularly in the inferior temporal gyus and supplementary motor areas. While rFDG correlated with CC in healthy subjects, this correlation was lost in AD patients. We suggest that AD pathology decouples the normal association between regional neural activity and functional segregation.