Individual Correspondence of Amyloid-β and Intrinsic Connectivity in the Posterior Default Mode Network Across Stages of Alzheimer's Disease

J Alzheimers Dis. 2017;58(3):763-773. doi: 10.3233/JAD-170096.

Abstract

In Alzheimer's disease (AD), amyloid-β (Aβ) pathology and intrinsic functional connectivity (iFC) interact. Across stages of AD, we expected individual spatial correspondence of Aβ and iFC to reveal both Aβ accumulation and its detrimental effects on iFC. We used resting-state functional magnetic imaging and Aβ imaging in a cross-sectional sample of 90 subjects across stages of AD and healthy older adults. Global and local correspondence of Aβ and iFC were assessed within the posterior default mode network (pDMN) by within-subject voxel-wise correlations. Beginning at preclinical stages, global Aβ-iFC correspondence was positive for the whole pDMN, showing that Aβ accumulates in areas of high connectivity, and reached a plateau at prodromal stages. Starting at preclinical stages, local correspondence was negative in network centers, indicating that Aβ reduces connectivity of the pDMN as a function of local plaque concentration, and peaked at prodromal stages. Positive global correspondence suggests that Aβ accumulation progresses along iFC, with this effect starting in preclinical stages, and being constant along clinical periods. Negative local correspondence suggests detrimental effects of Aβ on iFC in network centers, starting at preclinical stages, and peaking when first symptoms appear. Data reveal a complex trajectory of Aβ and iFC correspondence, affecting both Aβ accumulation and iFC impairments.

Keywords: Alzheimer’s disease; amyloid-β; intrinsic functional connectivity; mild cognitive impairment; multimodal imaging.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging*
  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / metabolism*
  • Brain / diagnostic imaging*
  • Brain / physiopathology*
  • Brain Mapping
  • Cross-Sectional Studies
  • Disease Progression
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mental Status and Dementia Tests
  • Multimodal Imaging
  • Neural Pathways / diagnostic imaging
  • Neural Pathways / physiopathology
  • Positron-Emission Tomography
  • Prodromal Symptoms
  • Rest

Substances

  • Amyloid beta-Peptides