Cited by 99Transcranial Magnetic Stimulation StudiesAlzheimer's disease research and treatmentsDementia and Cognitive Impairment Research

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

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Sprugnoli, Giulia, Munsch, Fanny, Cappon, Davide, Paciorek, Rachel, Macone, Joanna, Connor, Ann, El Fakhri, Georges, Salvador, Ricardo +7 more·2021·Alzheimer's Research & Therapy

Abstract

Background: Alzheimer’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. Methods: In 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. Results: No 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. Conclusions: Results 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 registration: Studies were registered separately on ClinicalTrials.gov (NCT03290326, registered on September 21, 2017; NCT03412604, registered on January 26, 2018).

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  • AD progression from the hippocampus to other parts of the brain disrupts circuitry-level connection.

    “AD progression from the hippocampus to other parts of the brain disrupts circuitry-level connection (e.g., [69]); that finding led to early clinical trials for inducing gamma-frequency or brain training to promote the connection among brain areas, and cognitive functions.”
  • It takes 10-20 years for AD to manifest itself.

    “It takes 10–20 years for AD to manifest itself (e.g., [5, 69]).”

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Authors
Sprugnoli, G., Munsch, F., Cappon, D., Paciorek, R., Macone, J., Connor, A., El Fakhri, G., Salvador, R., Ruffini, G., Donohoe, K., Shafi, M. M., Press, D., Alsop, D. C., Pascual Leone, A., & Santarnecchi, E.
Affiliations
  • University of Parma (IT)
  • Beth Israel Deaconess Medical Center (US)
  • Neuroelectrics Barcelona SLU (Spain) (ES)
  • Harvard University (US)
Corresponding author
Santarnecchi, Emiliano
Venue
Alzheimer's Research & Therapy
Published
2021-12
Volume
13
Issue
1
Pages
203-203
ISSN
1758-9193 (ISSN-L)
OpenAlex
W4200119814
Cited by
99
References
73
Citations by year
2026: 20 · 2025: 30 · 2024: 20 · 2023: 22 · 2022: 7
FWCI
4.86
Type
journal article
Language
en
Open access
Locations
  • Alzheimer s Research & Therapy (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Florence Research (University of Florence) (submittedVersion, cc-by)
Funders
  • defense advanced research projects agency (NCT03412604)
  • beth israel deaconess medical center (NCT03290326)
Topics
  • Life Sciences › Neuroscience › Neurology › Transcranial Magnetic Stimulation Studies
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
Alzheimer's disease, transcranial alternating current stimulation, cerebral blood flow, gamma oscillations, arterial spin labeling, episodic memory, temporal lobe, non-invasive brain stimulation, cognitive impairment
MeSH terms
Alzheimer Disease, Hippocampus, Humans, Perfusion, Cognitive Dysfunction, Transcranial Direct Current Stimulation

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