β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation

Nat Neurosci. 2015 Jul;18(7):1051-7. doi: 10.1038/nn.4035. Epub 2015 Jun 1.

Abstract

Independent evidence associates β-amyloid pathology with both non-rapid eye movement (NREM) sleep disruption and memory impairment in older adults. However, whether the influence of β-amyloid pathology on hippocampus-dependent memory is, in part, driven by impairments of NREM slow wave activity (SWA) and associated overnight memory consolidation is unknown. Here we show that β-amyloid burden in medial prefrontal cortex (mPFC) correlates significantly with the severity of impairment in NREM SWA generation. Moreover, reduced NREM SWA generation was further associated with impaired overnight memory consolidation and impoverished hippocampal-neocortical memory transformation. Furthermore, structural equation models revealed that the association between mPFC β-amyloid pathology and impaired hippocampus-dependent memory consolidation was not direct, but instead statistically depended on the intermediary factor of diminished NREM SWA. By linking β-amyloid pathology with impaired NREM SWA, these data implicate sleep disruption as a mechanistic pathway through which β-amyloid pathology may contribute to hippocampus-dependent cognitive decline in the elderly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / metabolism*
  • Aniline Compounds
  • Brain Waves / physiology*
  • Female
  • Hippocampus / physiopathology*
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Memory Disorders / physiopathology*
  • Memory, Episodic
  • Polysomnography
  • Positron-Emission Tomography
  • Prefrontal Cortex / metabolism*
  • Recognition, Psychology
  • Sleep Stages / physiology*
  • Sleep Wake Disorders / physiopathology*
  • Thiazoles

Substances

  • 2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole
  • Amyloid beta-Peptides
  • Aniline Compounds
  • Thiazoles