Although beta-amyloid (Aβ) deposition is a characteristic feature of Alzheimer's disease (AD), this pathology is commonly found in elderly normal controls (NC). The pattern of Aβ deposition as detected with Pittsburgh compound-B positron emission tomography (PIB-PET) imaging shows substantial spatial overlap with the default mode network (DMN), a group of brain regions that typically deactivates during externally driven cognitive tasks. In this study, we show that DMN functional connectivity (FC) during rest is altered with increasing levels of PIB uptake in NC. Specifically, FC decreases were identified in regions implicated in episodic memory (EM) processing (posteromedial cortex, ventral medial prefrontal cortex, and angular gyrus), whereas connectivity increases were detected in dorsal and anterior medial prefrontal and lateral temporal cortices. This pattern of decreases is consistent with previous studies that suggest heightened vulnerability of EM-related brain regions in AD, whereas the observed increases in FC may reflect a compensatory response.

Although deposition of β-amyloid (Aβ), a pathological hallmark of Alzheimer’s disease (AD), has also been reported in cognitively intact older people, its influence on brain structure and cognition during normal aging remains controversial. Using PET imaging with the radiotracer Pittsburgh compound B (PIB), structural MRI, and cognitive measures, we examined the relationships between Aβ deposition, gray matter volume, and cognition in older people without AD. Fifty-two healthy older participants underwent PIB-PET and structural MRI scanning and detailed neuropsychological tests. Results from the whole-brain voxel-based morphometry (VBM) analysis revealed that gray matter volume in the left inferior frontal cortex was negatively associated with amyloid deposition across all participants whereas reduced gray matter volume was shown in the posterior cingulate among older people with high amyloid deposition. When gray matter density measures extracted from these two regions were related to other brain regions by applying a structural covariance analysis, distinctive frontal and posterior brain networks were seen. Gray matter volume in these networks in relation to cognition, however, differed such that reduced frontal network gray matter volume was associated with poorer working memory performance while no relationship was found for the posterior network. The present findings highlight structural and cognitive changes in association with the level of Aβ deposition in cognitively intact normal elderly and suggest a differential role of Aβ – dependent gray matter loss in the frontal and posterior networks in cognition during normal aging.

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