Evidence map›Paper›PMID 41540503›Full record

ArticleBioelectronic medicine2026

Electrical stimulation of the vagus nerve improves amyloid pathology in delirium superimposed on dementia.

Chengcheng Song, Pau Yen Wu, William J Huffman, Jennifer David-Bercholz, Alicia Bedolla, Ravikanth Velagapudi, Ann Njoroge, Ramona M Rodriguiz, William C Wetsel, Danielle Rendina and 7 more

Abstract read
In one paragraph

Article in Bioelectronic medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Article
  3. What is new in delirium: A vascular etiology outlook.Alzheimer's & dementia (New York, N. Y.)
    Article
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

17 authors.

Chengcheng Song *Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Pau Yen Wu *Department of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
William J HuffmanDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Jennifer David-BercholzDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Alicia BedollaDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Ravikanth VelagapudiDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA.
Ann NjorogeDepartment of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University, Durham, NC, 27710, USA.
Ramona M RodriguizDepartment of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University, Durham, NC, 27710, USA.
William C WetselDepartment of Psychiatry and Behavioral Sciences, Mouse Behavioral and Neuroendocrine Analysis Core Facility, Duke University, Durham, NC, 27710, USA.
Danielle RendinaDepartment of Psychology and Neuroscience, Duke University, Durham, NC, 27710, USA.
Staci D BilboDepartment of Neurobiology, Duke University Medical Center, Durham, NC, 27710, USA.
Wesley ChiangDepartment of Chemistry, University of Rochester, Rochester, NY, USA.
Jessica C OguCenter for Neurotherapeutics Discovery, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
Harris A GelbardCenter for Neurotherapeutics Discovery, Department of Neurology, University of Rochester Medical Center, Rochester, NY, USA.
Ting YangDepartment of Medicine, Division of Nephrology, Duke University, Durham, NC, 27710, USA.
Warren M GrillDepartment of Biomedical Engineering, Duke University, Durham, NC, 27710, USA.
Niccolò TerrandoDepartment of Anesthesiology, Center for Translational Pain Medicine, Duke University Medical Center, Durham, NC, 27710, USA. niccolo.terrando@duke.edu.

Funding

Neurovascular dysfunction in delirium superimposed on dementiaR01AG057525 · NIA · DUKE UNIVERSITY · PI Niccolo Terrando · 2017 to 2026
$6.7M
Immunovascular interactions in postoperative delirium superimposed on dementia (DSD).RF1AG079138 · NIA · DUKE UNIVERSITY · PI GELBARD, HARRIS A, TERRANDO, NICCOLO · 2022 to 2025
$3.6M
IL-6 Trans-signaling increases vulnerability to Postoperative Cognitive Decline in Aging and Alzheimers DiseaseR01AG083979 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Mervyn Maze, Niccolo Terrando · 2024 to 2026
$3.2M
Bioelectronic rescue of cognitive impairment after surgeryR21AG055877 · NIA · DUKE UNIVERSITY · PI TERRANDO, NICCOLO · 2018 to 2019
$436k
Alzheimer's Association 2019-AARG-643070Alzheimer's Association AARF-24-1313412NIA NIH HHS R01 AG057525NIA NIH HHS R01 AG083979NIA NIH HHS R21 AG055877NIA NIH HHS RF1 AG079138NIH HHS R01-AG057525, R01-AG083979A1, RF1-AG079138, R21-AG055877
6 · The paper itself

Abstract

backgroundDelirium and delirium superimposed on dementia (DSD) are common complications affecting patients suffering from ongoing neurodegenerative pathologies. Peripheral surgical trauma can trigger neuroinflammation and ensuing DSD via mechanisms that remain poorly understood. Given the multifactorial therapeutic effects of neuromodulation, including vagal nerve stimulation, we have tested a minimally invasive approach to combat DSD following orthopedic surgery.

methodsWe performed orthopedic surgery on 5xFAD and CVN-AD mice and tested the efficacy of minimally invasive percutaneous vagus nerve stimulation (pVNS). We applied immunohistochemical, biochemical, and behavioral assays to evaluate the impact of surgery on postoperative delirium on DSD pathology in Alzheimer’s disease-like mice. To confirm the role of systemic factors in neuroinflammation and amyloid-β dyshomeostasis, we conducted experiments using interleukin-6 (IL-6), a cytokine commonly upregulated in postoperative delirium and in vitro co-culture assays for validation.

resultsIn AD-like mice surgery induced acute changes in amyloid-β; perioperative treatment with pVNS effectively reduced amyloid-β load, plaque sphericity, and neuronal loss. The rescue of these pathological hallmarks led to improved delirium-like behavior, as demonstrated by the 5-choice serial reaction time task on postoperative days 1 and 2. pVNS improved microglial morphology, particularly near amyloid-β plaques. Acute isolation of microglial cells from 5xFAD mice after surgery indicated that pVNS partially enhanced key Disease-Associated Microglia (DAM) markers. The contribution of pro-inflammatory cytokines to amyloid-β aggregation was validated using an in vitro transwell culture model following Cytomix exposure, which also caused endothelial barrier disruption. Finally, we isolated IL-6 as a well-established biomarker of postoperative delirium and described its role in DSD pathology following systemic administration.

conclusionThese findings establish a role for neuromodulation after pVNS in regulating perioperative immunity and advance a new paradigm for perioperative interventions in patients at risk for DSD.

Indexed as

Amyloid-βDeliriumIL-6InflammationMicrogliaVagus nerve

Identifiers

PMID41540503
PMCPMC12809983

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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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 Socratic graph.