There is striking overlap between the spatial distribution of amyloid-? pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-? and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-? plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the default mode network. However, the observed spatial extent of amyloid-? exceeds these tightly circumscribed areas, suggesting that previous studies may have underestimated the negative impact of amyloid-? on intrinsic connectivity. We hypothesized that the known positive baseline correlation between patterns of amyloid-? and intrinsic connectivity may mask the larger extent of the negative effects of amyloid-? on connectivity. Crucially, a test of this hypothesis requires the within-patient comparison of intrinsic connectivity and amyloid-? distributions. Here we compared spatial patterns of amyloid-?-plaques (measured by Pittsburgh compound B positron emission tomography) and intrinsic functional connectivity (measured by resting-state functional magnetic resonance imaging) in patients with prodromal Alzheimer's disease via spatial correlations in intrinsic networks covering fronto-parietal heteromodal cortices. At the global network level, we found that amyloid-? and intrinsic connectivity patterns were positively correlated in the default mode and several fronto-parietal attention networks, confirming that amyloid-? aggregates in areas of high intrinsic connectivity on a within-network basis. Further, we saw an internetwork gradient of the magnitude of correlation that depended on network plaque-load. After accounting for this globally positive correlation, local amyloid-?-plaque concentration in regions of high connectivity co-varied negatively with intrinsic connectivity, indicating that amyloid-? pathology adversely reduces connectivity anywhere in an affected network as a function of local amyloid-?-plaque concentration. The local negative association between amyloid-? and intrinsic connectivity was much more pronounced than conventional group comparisons of intrinsic connectivity would suggest. Our findings indicate that the negative impact of amyloid-? on intrinsic connectivity in heteromodal networks is underestimated by conventional analyses. Moreover, our results provide first within-patient evidence for correspondent patterns of amyloid-? and intrinsic connectivity, with the distribution of amyloid-? pathology following functional connectivity gradients within and across intrinsic networks.     «

There is striking overlap between the spatial distribution of amyloid-? pathology in patients with Alzheimer's disease and the spatial distribution of high intrinsic functional connectivity in healthy persons. This overlap suggests a mechanistic link between amyloid-? and intrinsic connectivity, and indeed there is evidence in patients for the detrimental effects of amyloid-? plaque accumulation on intrinsic connectivity in areas of high connectivity in heteromodal hubs, and particularly in the...     »