Evidence map›Paper›PMID 26996255›Full record

ReviewSleep medicine reviews2017

Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease.

Jonathan Cedernaes, Ricardo S Osorio, Andrew W Varga, Korey Kam, Helgi B Schiöth, Christian Benedict

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Sleep medicine reviews, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
99citing papers in PubMed, 3 pooled it
12.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

99 citing papers in PubMed, 3 syntheses or guidelines pooled it, 190 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Article
  6. Article
  7. Article
  8. Emerging directions in tauopathy research.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
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  10. Article
  11. Review
  12. Review
  13. bioRxiv : the preprint server for biology · 2025
    Article
  14. Neuronal oscillations in cognition: Down syndrome as a model of mouse to human translation.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2025
    Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

39 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 2 countries.

Jonathan CedernaesDepartment of Neuroscience, Uppsala University, Sweden. Electronic address: Jonathan.Cedernaes@neuro.uu.se.
Ricardo S OsorioCenter for Brain Health, NYU Langone Medical Center, New York, NY, USA. Electronic address: Ricardo.Osorio@nyumc.org.
Andrew W VargaNYU Sleep Disorders Center, NYU Langone Medical Center, New York, NY, USA.
Korey KamNYU Sleep Disorders Center, NYU Langone Medical Center, New York, NY, USA.
Helgi B SchiöthDepartment of Neuroscience, Uppsala University, Sweden.
Christian BenedictDepartment of Neuroscience, Uppsala University, Sweden. Electronic address: Christian.Benedict@neuro.uu.se.
NYU Langone Health · USUppsala University · SE

Funding

PSYCHOSOCIAL COREP30AG008051 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI SHAO, YONGZHAO · 1990 to 2019
$36.1M
Sleep Disordered Breathing in normal elderly and risk for Alzheimers DiseaseR01HL118624 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI OSORIO, RICARDO S · 2013 to 2016
$2.7M
Brain Sleep Clearance of Amyloid-Beta Peptides Study (Brain SCRAPS)R21AG049348 · NIA · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI OSORIO, RICARDO S · 2015 to 2016
$454k
NHLBI NIH HHS R01 HL118624NIA NIH HHS P30 AG008051NIA NIH HHS R21 AG049348
6 · The paper itself

Abstract

During wakefulness, extracellular levels of metabolites in the brain increase. These include amyloid beta (Aβ), which contributes to the pathogenesis of Alzheimer's disease (AD). Counterbalancing their accumulation in the brain, sleep facilitates the removal of these metabolites from the extracellular space by convective flow of the interstitial fluid from the para-arterial to the para-venous space. However, when the sleep-wake cycle is disrupted (characterized by increased brain levels of the wake-promoting neuropeptide orexin and increased neural activity), the central nervous system (CNS) clearance of extracellular metabolites is diminished. Disruptions to the sleep-wake cycle have furthermore been linked to increased neuronal oxidative stress and impaired blood-brain barrier function - conditions that have also been proposed to play a role in the development and progression of AD. Notably, recent human and transgenic animal studies have demonstrated that AD-related pathophysiological processes that occur long before the clinical onset of AD, such as Aβ deposition in the brain, disrupt sleep and circadian rhythms. Collectively, as proposed in this review, these findings suggest the existence of a mechanistic interplay between AD pathogenesis and disrupted sleep-wake cycles, which is able to accelerate the development and progression of this disease.

Indexed as

Circadian RhythmAgingAlzheimer DiseaseAmyloid beta-PeptidesAnimalsBlood-Brain BarrierBrainDisease Models, AnimalHumansSleep Wake Disorderstau ProteinsAmyloid beta-Peptidestau ProteinsAgingAmyloid betaBlood brain barrierCircadian misalignmentNeurodegenerationOrexinOxidative stressSleep disruptionSlow-wave sleepTau

Identifiers

PMID26996255
PMCPMC4981560
OpenAlexW2265194371

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.