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β-amyloid disrupts human NREM slow waves and related hippocampus-dependent memory consolidation
Open accessAbstract
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.
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Cognitively non-impaired adults with decreased SWS exhibit increased amyloidβ burden and worse sleep-mediated episodic memory consolidation.
“Furthermore, patients with AD have less SWS, and cognitively non-impaired adults with decreased SWS exhibit increased amyloid𝛃 burden and worse sleep-mediated episodic memory consolidation [6, 7].”
From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [6]
Patients with Alzheimer's disease have less SWS.
“Furthermore, patients with AD have less SWS, and cognitively non-impaired adults with decreased SWS exhibit increased amyloid𝛃 burden and worse sleep-mediated episodic memory consolidation [6, 7].”
From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [6]
Previous studies indicate a relationship between decreased SWS, cognitive deficits, and amyloidβ pathology as revealed through molecular PET even in cognitively non-impaired individuals.
“Based on previous studies that indicate a relationship between decreased SWS, cognitive deficits, and amyloid𝛃 pathology as revealed through molecular PET even in cognitively non-impaired individuals”
From Long-Term Trazodone Use and Cognition: A Potential Therapeutic Role for Slow-Wave Sleep Enhancers (2019) · cites this paper as [6]
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Metadata
- Authors
- Mander, B. A., Marks, S. M., Vogel, J. W., Rao, V., Lu, B., Saletin, J. M., Ancoli-Israel, S., Jagust, W. J., & Walker, M. P.
- Affiliations
- University of California, Berkeley (US)
- California Pacific Medical Center (US)
- Lawrence Berkeley National Laboratory (US)
- Corresponding author
- Mander, Bryce A
- Walker, Matthew P
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2015-06-01
- Volume
- 18
- Issue
- 7
- Pages
- 1051-1057
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC4482795
- OpenAlex
- W2161166547
- Cited by
- 569
- References
- 17
- Citations by year
- 2026: 57 · 2025: 50 · 2024: 56 · 2023: 57 · 2022: 50 · 2021: 62 · 2020: 59 · 2019: 56 · 2018: 27 · 2017: 42 · 2016: 45 · 2015: 7
- FWCI
- 19.86
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Funders
- National Institutes of Health
- National Institute on Aging (F32AG039170, R01AG031164, R01AG034570)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- amyloid-beta, sleep disruption, medial prefrontal cortex, older adults, cognitive decline, Alzheimer's disease, memory impairment
- MeSH terms
- Aged, Aged, 80 and over, Aniline Compounds, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Sleep Wake Disorders, Sleep Stages, Thiazoles, Amyloid beta-Peptides, Polysomnography, Prefrontal Cortex, Recognition, Psychology, Positron-Emission Tomography, Brain Waves, Memory, Episodic
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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