Amyloid plaques disrupt resting state default mode network connectivity in cognitively normal elderly

Abstract

Background: Important functional connections within the default mode network (DMN) are disrupted in Alzheimer's disease (AD), likely from amyloid-beta (Abeta) plaque-associated neuronal toxicity. Here, we sought to determine if pathological effects of Abeta amyloid plaques could be seen, even in the absence of a task, by examining functional connectivity in cognitively normal participants with and without preclinical amyloid deposition.

Methods: Participants with Alzheimer's disease (AD) (n = 35) were compared with 68 cognitively normal participants who were further subdivided by positron emission tomography (PET) Pittsburgh Compound-B (PIB) imaging into those without evidence of brain amyloid (PIB-) and those with brain amyloid (PIB+) deposition.

Results: Resting state functional magnetic resonance imaging (fMRI) demonstrated that, compared with the PIB- group, the PIB+ group differed significantly in functional connectivity of the precuneus to hippocampus, parahippocampus, anterior cingulate, dorsal cingulate, gyrus rectus, superior precuneus, and visual cortex. These differences were in the same regions and in the same direction as differences found in the AD group.

Conclusions: Thus, before any manifestations of cognitive or behavioral changes, there were differences in resting state connectivity in cognitively normal subjects with brain amyloid deposition, suggesting that early manifestation of Abeta toxicity can be detected using resting state fMRI.

Figure 1. Altered Functional Connectivity to the Precuneus

All images are shown in medial sagittal section and identify statistically significant regional differences in functional connectivity of the precuneus between AD and (PIB−) cognitively normal individuals (blue) and between (PIB+) and (PIB−) cognitively normal individuals (red). The top left (1a) and right (1c) images display the left medial surfaces in AD vs PIB− and PIB+ vs PIB− participants, respectively. The second row left (1b) and right (1d) images display the right medial sagittal surfaces in the AD vs PIB− and PIB+ vs PIB− participants, respectively. The regions identified were in visual cortex-(VC) (both L and R), L hippocampus—(L hip), L parahippocampus—(L parahip), L anterior cingulate (AC), L (AD only) and R gyrus rectus (GR)(both groups). For brevity, not shown are the dorsal cingulate (DC) and superior precuneus (sup PC) regions. The graph compares regional correlation magnitudes for AD, PIB+ and PIB− individuals. *p-values denote significant differences in connectivity between (PIB+) and (PIB−) groups.