Evidence map›Paper›PMID 34930421›Full record

Trial reportAlzheimer's research & therapy2021

Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease.

Giulia Sprugnoli, Fanny Munsch, Davide Cappon, Rachel Paciorek, Joanna Macone, Ann Connor, Georges El Fakhri, Ricardo Salvador, Giulio Ruffini, Kevin Donohoe and 5 more

4 registry-linked trialsOpen access · goldAbstract readClinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 4 registered trials, which are not on this map. Cited by 60 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed, 4 pooled it
6.4field-weighted citation impact, top 2% 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.

NCT03290326 nacompletednot on this map

Feasibility and Safety of a High-Frequency Transcranial Alternating Current Stimulation Intervention for Amyloid-β Reduction in Alzheimer's Disease

TypeinterventionalSponsorMassachusetts General HospitalRan2017 to 2019Enrolled17ConditionsAlzheimer DiseaseArmsTranscranial Alternating Current Stimulation (tACS)
NCT03412604 nacompletednot on this map

Effect of Modulating Gamma Oscillations by Transcranial Alternating Current Stimulation on Brain Structure and Function in Humans

TypeinterventionalSponsorMassachusetts General HospitalRan2018 to 2019Enrolled5ConditionsAlzheimer DiseaseArmsTranscranial Alternating Current Stimulation (tACS)
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

60 citing papers in PubMed, 4 syntheses or guidelines pooled it, 91 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 3 institutions in 3 countries.

Giulia SprugnoliBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.ORCID 0000-0003-4621-9537
Fanny MunschDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Davide CapponBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Rachel PaciorekBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Joanna MaconeBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ann ConnorBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Georges El FakhriCenter for Advanced Medical Imaging Sciences, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Ricardo SalvadorNeuroelectrics, Barcelona, Spain.
Giulio RuffiniNeuroelectrics, Barcelona, Spain.
Kevin DonohoeCenter for Advanced Medical Imaging Sciences, Division of Nuclear Medicine and Molecular Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
Mouhsin M ShafiBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Daniel PressBerenson-Allen Center for Non-Invasive Brain Stimulation, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
David C AlsopDepartment of Radiology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Alvaro Pascual LeoneHinda and Arthur Marcus Institute for Aging Research and Deanna and Sidney Wolk Center for Memory Health, Hebrew Senior Life, Boston, MA, USA.
Emiliano SantarnecchiPrecision Neuroscience & Neuromodulation Program, Gordon Center for Medical Imaging, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. esantarnecchi@mgh.harvard.edu.
Beth Israel Deaconess Medical Center · USHarvard University · USUniversity of Parma · IT

Funding

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
Treating hyperexcitability in Alzheimer’s disease with levetiracetam to improve brain function and cognitionR01AG060987 · NIA · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SHAFI, MOUHSIN · 2019 to 2023
$3.0M
NIA NIH HHS R01 AG060981NIA NIH HHS R01 AG060987NIBIB NIH HHS P41 EB022544
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection.

methodsIn two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments.

resultsNo serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band.

conclusionsResults suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients.

trial registrationStudies were registered separately on ClinicalTrials.gov ( NCT03290326 , registered on September 21, 2017; NCT03412604 , registered on January 26, 2018).

Indexed as

Alzheimer DiseaseCognitive DysfunctionTranscranial Direct Current StimulationHippocampusHumansPerfusionCBFCerebral blood flowDementiaEEGGamma activityGamma bandHippocampusNeuromodulationNeurostimulationtES

Identifiers

PMID34930421
PMCPMC8690894
OpenAlexW4200119814

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

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.