Amyloid Deposition Is Associated with Impaired Default Network Function in Older Persons without Dementia

Reisa A. Sperling, Peter S. LaViolette, Kelly O'Keefe, Jacqueline O'Brien, Dorene M. Rentz, Maija Pihlajamaki, Gad Marshall, Bradley T. Hyman, Dennis J. Selkoe, Trey Hedden, Randy L. Buckner, J. Alex Becker, Keith A. Johnson

Research output: Contribution to journalArticlepeer-review

823 Scopus citations

Abstract

Alzheimer's disease (AD) has been associated with functional alterations in a distributed network of brain regions linked to memory function, with a recent focus on the cortical regions collectively known as the default network. Posterior components of the default network, including the precuneus and posterior cingulate, are particularly vulnerable to early deposition of amyloid β-protein, one of the hallmark pathologies of AD. In this study, we use in vivo amyloid imaging to demonstrate that high levels of amyloid deposition are associated with aberrant default network functional magnetic resonance imaging (fMRI) activity in asymptomatic and minimally impaired older individuals, similar to the pattern of dysfunction reported in AD patients. These findings suggest that amyloid pathology is linked to neural dysfunction in brain regions supporting memory function and provide support for the hypothesis that cognitively intact older individuals with evidence of amyloid pathology may be in early stages of AD.

Original languageEnglish
Pages (from-to)178-188
Number of pages11
JournalNeuron
Volume63
Issue number2
DOIs
StatePublished - 30 Jul 2009
Externally publishedYes

Keywords

  • HUMDISEASE
  • MOLNEURO
  • SYSNEURO

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