Evidence map›Paper›PMID 34958021›Full record

ArticleJournal of Alzheimer's disease : JAD2022

Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer's Disease: A Case Series.

Maeva Dhaynaut, Giulia Sprugnoli, Davide Cappon, Joanna Macone, Justin S Sanchez, Marc D Normandin, Nicolas J Guehl, Giacomo Koch, Rachel Paciorek, Ann Connor and 5 more

2 registry-linked trialsOpen access · bronzeAbstract readCase Reports
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 54 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
54citing papers in PubMed, 3 pooled it
3.9field-weighted citation impact, top 6% 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.

NCT05999916 nacompletednot on this mapstarted 2023, after this paper: background citation

A Prospective, Single-Arm, Monocentric Pilot Study to Evaluate the Safety and Feasibility of Transcranial Alternate Current Stimulation With the Miamind Neurostimulator in Healthy Participants

TypeinterventionalSponsorBottneuro AGRan2023 to 2024Enrolled8ConditionsHealthy Participants, Healthy PopulationArmsPersonalized Miamind Neurostimulator
NCT06826261 naactive not recruitingnot on this mapstarted 2023, after this paper: background citation

Home-based Transcranial Electrical Stimulation (tES) in Alzheimer's Disease

TypeinterventionalSponsorI.R.C.C.S. Fondazione Santa LuciaRan2023 to 2025Enrolled30ConditionsAlzheimer DiseaseArmstranscranial alternating current stimulation, sham transcranial alternating current stimulation
3 · Its place in the literature

Who cites it

54 citing papers in PubMed, 3 syntheses or guidelines pooled it, 71 citations in OpenAlex.

  1. Effects of transcranial alternating current stimulation on cognitive function in older adults: a systematic review and meta-analysis of randomized controlled trials.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
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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

15 authors at 7 institutions in 2 countries.

Maeva DhaynautGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Giulia SprugnoliBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Davide CapponBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joanna MaconeBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Justin S SanchezGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Marc D NormandinGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Nicolas J GuehlGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Giacomo KochSanta Lucia Foundation IRCCS, Rome, Italy.
Rachel PaciorekBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ann ConnorBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Daniel PressBerenson-Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Keith JohnsonGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Alvaro Pascual-LeoneHinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew SeniorLife, Boston, MA, USA.
Georges El FakhriGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Emiliano SantarnecchiGordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Berenson Allen Center for Noninvasive Brain Stimulation · USMassachusetts General Hospital · USBeth Israel Deaconess Medical Center · USGordon Center for Medical Imaging · USFondazione Santa Lucia · ITHarvard University · USHebrew SeniorLife · US

Funding

The Role of Inflammation in the Pathophysiology of Delirium and its Associated Long-Term Cognitive DeclineP01AG031720 · NIA · HEBREW REHABILITATION CENTER FOR AGED · PI INOUYE, SHARON K. · 2010 to 2022
$26.7M
Unified Joint Statistical Reconstruction of PET & MRP41EB022544 · NIBIB · YALE UNIVERSITY · PI Georges El Fakhri · 2017 to 2026
$14.8M
Gamma Induction for Amyloid Clearance in Alzheimer’s DiseaseR01AG060981 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI SANTARNECCHI, EMILIANO · 2019 to 2023
$3.5M
The Development and Human Translation of Temporal Interference Brain StimulationR01MH117063 · NIMH · BETH ISRAEL DEACONESS MEDICAL CENTER · PI PRESS, DANIEL Z. · 2018 to 2021
$2.8M
NIA NIH HHS P01 AG031720NIA NIH HHS R01 AG060981NIBIB NIH HHS P41 EB022544NIMH NIH HHS R01 MH117063
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is characterized by diffuse amyloid-β (Aβ) and phosphorylated Tau (p-Tau) aggregates as well as neuroinflammation. Exogenously-induced 40 Hz gamma oscillations have been showing to reduce Aβ and p-Tau deposition presumably via microglia activation in AD mouse models.

objectiveWe aimed to translate preclinical data on gamma-induction in AD patients by means of transcranial alternating current stimulation (tACS).

methodsFour participants with mild-to-moderate AD received 1 h of daily 40 Hz (gamma) tACS for 4 weeks (Monday to Friday) targeting the bitemporal lobes (20 h treatment duration). Participant underwent Aβ, p-Tau, and microglia PET imaging with [11C]-PiB, [18F]-FTP, and [11C]-PBR28 respectively, before and after the intervention along with electrophysiological assessment.

resultsNo adverse events were reported, and an increase in gamma spectral power on EEG was observed after the treatment. [18F]-FTP PET revealed a significant decrease over 2% of p-Tau burden in 3/4 patients following the tACS treatment, primarily involving the temporal lobe regions targeted by tACS and especially mesial regions (e.g., entorhinal cortex). The amount of intracerebral Aβ as measured by [11C]-PiB was not significantly influenced by tACS, whereas 1/4 reported a significant decrease of microglia activation as measured by [11C]-PBR28.

conclusiontACS seems to represent a safe and feasible option for gamma induction in AD patients, with preliminary evidence of a possible effect on protein clearance partially mimicking what is observed in animal models. Longer interventions and placebo control conditions are needed to fully evaluate the potential for tACS to slow disease progression.

Indexed as

Alzheimer DiseaseTranscranial Direct Current StimulationAgedAmyloid beta-PeptidesAnimalsBrainEntorhinal CortexFemaleHumansMaleMiceMicrogliaPositron-Emission Tomographytau ProteinsTemporal LobeAmyloid beta-Peptidestau ProteinsAmyloiddementiaelectroencephalographygammaneurostimulationpositron-emission tomographyprotein clearanceprotein misfoldingtautranscranial electrical stimulation

Identifiers

PMID34958021
PMCPMC9023125
OpenAlexW4200006726

What OpenQuestion holds

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Registered trials

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.