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Cereb Cortex. 2016 Feb;26(2):695-707. doi: 10.1093/cercor/bhu259. Epub 2014 Nov 7.

Effects of Beta-Amyloid on Resting State Functional Connectivity Within and Between Networks Reflect Known Patterns of Regional Vulnerability.

Author information

  • 1Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
  • 2Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.
  • 3Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA Helen Wills Neuroscience Institute, University of California, Berkeley, CA 94720, USA.

Abstract

Beta-amyloid (Aβ) deposition is one of the hallmarks of Alzheimer's disease (AD). However, it is also present in some cognitively normal elderly adults and may represent a preclinical disease state. While AD patients exhibit disrupted functional connectivity (FC) both within and between resting-state networks, studies of preclinical cases have focused primarily on the default mode network (DMN). The extent to which Aβ-related effects occur outside of the DMN and between networks remains unclear. In the present study, we examine how within- and between-network FC are related to both global and regional Aβ deposition as measured by [(11)C]PIB-PET in 92 cognitively normal older people. We found that within-network FC changes occurred in multiple networks, including the DMN. Changes of between-network FC were also apparent, suggesting that regions maintaining connections to multiple networks may be particularly susceptible to Aβ-induced alterations. Cortical regions showing altered FC clustered in parietal and temporal cortex, areas known to be susceptible to AD pathology. These results likely represent a mix of local network disruption, compensatory reorganization, and impaired control network function. They indicate the presence of Aβ-related dysfunction of neural systems in cognitively normal people well before these areas become hypometabolic with the onset of cognitive decline.

KEYWORDS:

PIB-PET; aging; beta-amyloid; functional connectivity; resting-state fMRI

PMID:
25405944
PMCID:
PMC4712800
DOI:
10.1093/cercor/bhu259
[PubMed - indexed for MEDLINE]
Free PMC Article
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