Evidence map›Paper›PMID 35607946›Full record

Trial reportAnnals of neurology2022

Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease.

Alberto Benussi, Valentina Cantoni, Mario Grassi, Lucie Brechet, Christoph M Michel, Abhishek Datta, Chris Thomas, Stefano Gazzina, Maria Sofia Cotelli, Marta Bianchi and 11 more

5 registry-linked trialsOpen access · hybridAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Annals of neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 5 registered trials, which are not on this map. Cited by 95 papers, 10 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
95citing papers in PubMed, 10 pooled it
15.1field-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.

NCT05643326 nacompletednot on this map

Markers of Clinical and Biological Response to Home Delivered Transcranial Alternating Current Stimulation (tACS) in Patients With Alzheimer's Disease

TypeinterventionalSponsorAzienda Socio Sanitaria Territoriale degli Spedali Civili di BresciaRan2022 to 2024Enrolled53ConditionsAlzheimer DiseaseArms40 Hz transcranial alternating current stimulation, Sham stimulation
NCT05708001 narecruitingnot on this mapstarted 2023, after this paper: background citation

Improvement of Memory in Mild Cognitive Impairment (MCI) Using Transcranial Alternating Current Stimulation (tACS) Guided by EEG and MRI: a Randomized, Sham-controlled, Parallel-arm, Double-blind Study

TypeinterventionalSponsorLucie BréchetRan2023 to 2027Enrolled40ConditionsMild Cognitive ImpairmentArmstranscranial alternating current stimulation (tACS), high-density electroencephalography (hdEEG), Montreal Cognitive Assessment (MoCA)
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
NCT06202872 nacompletednot on this mapstarted 2024, after this paper: background citation

Memory Enhancement Using Transcranial Alternating Current Stimulation

TypeinterventionalSponsorAmsterdam UMC, location VUmcRan2024 to 2026Enrolled26ConditionsAlzheimer Disease, Mild Cognitive ImpairmentArmsGamma (40 Hz) tACS at the precuneus region, Sham tACS at the precuneus region
NCT07505784 narecruitingnot on this mapstarted 2026, after this paper: background citation

Cross-over Study to Evaluate the Safety, Tolerability, and Clinical Efficacy of Transcranial Alternating Current Stimulation (tACS) in Patients With Frontotemporal Dementia

TypeinterventionalSponsorIRCCS Centro San Giovanni di Dio FatebenefratelliRan2026 to 2027Enrolled30ConditionsTranscranial Alternating Current Stimulation, Frontotemporal Dementia (FTD)ArmsTranscranial Alternating Current Stimulation, Sham Transcranial Alternating Current Stimulation
3 · Its place in the literature

Who cites it

95 citing papers in PubMed, 10 syntheses or guidelines pooled it, 145 citations in OpenAlex.

  1. Efficacy of transcranial alternating current stimulation on cognitive function in patients with dementia: 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 · 2026
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  3. Efficacy and safety of tACS in older adults with cognitive impairment: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  5. 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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35 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

21 authors at 8 institutions in 5 countries.

Alberto BenussiNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.ORCID 0000-0002-8703-6940
Valentina CantoniNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Mario GrassiDepartment of Brain and Behavioural Sciences, Medical and Genomic Statistics Unit, University of Pavia, Pavia, Italy.
Lucie BrechetFunctional Brain Mapping Laboratory, Department of Fundamental Neuroscience, University of Geneva, Geneva, Switzerland.
Christoph M MichelFunctional Brain Mapping Laboratory, Department of Fundamental Neuroscience, University of Geneva, Geneva, Switzerland.
Abhishek DattaResearch & Development, Soterix Medical, Inc., New York, USA.
Chris ThomasResearch & Development, Soterix Medical, Inc., New York, USA.
Stefano GazzinaNeurophysiology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy.
Maria Sofia CotelliNeurology Unit, Valle Camonica Hospital, Brescia, Italy.
Marta BianchiNeurology Unit, Valle Camonica Hospital, Brescia, Italy.
Enrico PremiStroke Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy.
Yasmine GadolaNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Maria CotelliNeuropsychology Unit, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
Marta PengoDepartment of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Federica PerroneNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Maria ScolaroNeurophysiology Unit, Department of Neurological and Vision Sciences, ASST Spedali Civili, Brescia, Italy.
Silvana ArchettiClinical Chemistry Laboratory, Diagnostic Department, ASST Spedali Civili Brescia, Brescia, Italy.
Eino SoljeInstitute of Clinical Medicine, Neurology, University of Eastern Finland, Kuopio, Finland.ORCID 0000-0001-9940-9524
Alessandro PadovaniNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
Alvaro Pascual-LeoneDepartment of Neurology, Harvard Medical School, Boston, Massachusetts, USA.ORCID 0000-0001-8975-0382
Barbara BorroniNeurology Unit, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.ORCID 0000-0001-9340-9814
Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia · ITUniversity of Brescia · ITCentro San Giovanni di Dio Fatebenefratelli · ITSoterix Medical (United States) · USUniversity of Geneva · CHHarvard University · USUniversity of Eastern Finland · FIUniversity of Pavia · IT

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThis study aimed to assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (γ-tACS) applied over the precuneus can improve episodic memory and modulate cholinergic transmission by modulating cerebral rhythms in early Alzheimer's disease (AD).

methodsIn this randomized, double-blind, sham controlled, crossover study, 60 AD patients underwent a clinical and neurophysiological evaluation including assessment of episodic memory and cholinergic transmission pre and post 60 minutes treatment with γ-tACS targeting the precuneus or sham tACS. In a subset of 10 patients, EEG analysis and individualized modelling of electric field distribution were carried out. Predictors to γ-tACS efficacy were evaluated.

resultsWe observed a significant improvement in the Rey Auditory Verbal Learning (RAVL) test immediate recall (p < 0.001) and delayed recall scores (p < 0.001) after γ-tACS but not after sham tACS. Face-name associations scores improved with γ-tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after γ-tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to γ-tACS. Clinical improvement correlated with the increase in gamma frequencies in posterior regions and with the amount of predicted electric field distribution in the precuneus.

interpretationPrecuneus γ-tACS, able to increase γ-power activity on the posterior brain regions, showed a significant improvement of episodic memory performances, along with restoration of intracortical excitability measures of cholinergic transmission. Response to γ-tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022;92:322-334.

Indexed as

Alzheimer DiseaseMemory, EpisodicTranscranial Direct Current StimulationBrainCholinergic AgentsCross-Over StudiesHumansCholinergic Agents

Identifiers

PMID35607946
PMCPMC9546168
OpenAlexW4282940626

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.