title: β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation.
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.
authors.affiliation: Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA.
authors.forename: Bryce A
authors.initials: BA
authors.lastname: Mander
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
authors.forename: Shawn M
authors.identifier: 0000000198848461
authors.initials: SM
authors.lastname: Marks
authors.affiliation: Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
authors.forename: Jacob W
authors.initials: JW
authors.lastname: Vogel
authors.affiliation: Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Rao
authors.affiliation: Division of Pulmonary and Critical Care Medicine, California Pacific Medical Center, San Francisco, California, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Lu
authors.affiliation: Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA.
authors.forename: Jared M
authors.initials: JM
authors.lastname: Saletin
authors.affiliation: Department of Psychiatry, University of California, San Diego, La Jolla, California, USA.
authors.forename: Sonia
authors.initials: S
authors.lastname: Ancoli-Israel
authors.affiliation: 1] Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA. [2] Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: William J
authors.initials: WJ
authors.lastname: Jagust
authors.affiliation: 1] Sleep and Neuroimaging Laboratory, University of California, Berkeley, California, USA. [2] Helen Wills Neuroscience Institute, University of California, Berkeley, California, USA.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: Walker
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000814:Aniline Compounds; D058256:Brain Waves / Q000502:physiology*; D005260:Female; D006624:Hippocampus / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000503:physiopathology*; D061212:Memory, Episodic; D017286:Polysomnography; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000378:metabolism*; D021641:Recognition, Psychology; D012894:Sleep Stages / Q000502:physiology*; D012893:Sleep Wake Disorders / Q000503:physiopathology*; D013844:Thiazoles
chemical_list: C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D013844:Thiazoles