Clinical trial NCT06202872: Memory Enhancement Using Transcranial Alternating Current Stimulation
Official title: Memory Enhancement Using Transcranial Alternating Current Stimulation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Keywords: Alzheimer's disease
Transcranial alternating current stimulation
Episodic memory
Magnetoencephalography
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2024-01-12
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, sham-controlled, crossover trial
Primary purpose: TREATMENT

Brief summary: The 32 million Alzheimer's disease (AD) and 69 million prodromal AD patients worldwide contribute to a large economic burden. Effective and safe therapies that slow or prevent the progression from mild cognitive impairment (MCI) to AD are therefore of high priority. Transcranial alternating current stimulation (tACS) is a safe and patient-friendly non-invasive brain stimulation technique that serves as a potential candidate for reducing and/or slowing cognitive impairment. Application of tACS in the gamma frequency range, specifically around 40 Hz, has been studied in patients with AD and MCI due to AD. In these patients, a single session of 40 Hz tACS at the precuneus showed to improve episodic memory and to increase gamma power, as measured with electroencephalography. These findings will be replicated in the current study in patients with MCI due to AD, using magnetoencephalography (MEG) recorded before, during and after tACS. In this way, brain activity and network changes that underlie this improvement in episodic memory can be studied with greater temporal and spatial detail.


Eligibility criteria: Inclusion Criteria:

* Recent (not more than 6 months ago) amnestic MCI diagnosis, which consensus is obtained in a multidisciplinary meeting after an extended multidisciplinary test battery at the memory clinic, including confirmation of AD pathology with cerebrospinal fluid biomarkers: abnormal p-tau/Aβ42 ratio of \> 0.023

Exclusion Criteria:

* Suffering from serious neurological, psychiatric or somatic comorbidity
* Suffering from epileptic seizures or severe claustrophobia
* Intensive use of psychoactive medication
* Having a cardiac pacemaker, internal cardiac defibrillator or other intracorporeal device that interferes with MEG recordings

Primary outcomes:
measure: Change in Rey Auditory Verbal Learning test scores
timeFrame: Immediately before and after intervention
measure: Change in Face-Name Association Task scores
timeFrame: Immediately before and after intervention
Secondary outcomes:
measure: Change in spectral source space resting-state MEG (relative power)
timeFrame: Immediately before and after intervention
measure: Change in spectral source space resting-state MEG (posterior peak frequency)
timeFrame: Immediately before and after intervention
measure: Change in functional connectivity source space resting-state MEG (AEC-c)
timeFrame: Immediately before and after intervention
measure: Change in functional connectivity source space resting-state MEG (PLI)
timeFrame: Immediately before and after intervention
measure: Change in source space resting-state MEG network structure (MST variables)
timeFrame: Immediately before and after intervention
measure: Change in source space resting-state MEG network structure (clustering coefficient and path length)
timeFrame: Immediately before and after intervention
measure: Change in source space resting-state MEG network structure (modulatory index, degree and eigenvector centrality)
timeFrame: Immediately before and after intervention
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, The Netherlands
state: Noord-Holland
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: Willem de Haan, dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benussi A, Cantoni V, Cotelli MS, Cotelli M, Brattini C, Datta A, Thomas C, Santarnecchi E, Pascual-Leone A, Borroni B. Exposure to gamma tACS in Alzheimer's disease: A randomized, double-blind, sham-controlled, crossover, pilot study. Brain Stimul. 2021 May-Jun;14(3):531-540. doi: 10.1016/j.brs.2021.03.007. Epub 2021 Mar 21.
citation: Benussi A, Cantoni V, Grassi M, Brechet L, Michel CM, Datta A, Thomas C, Gazzina S, Cotelli MS, Bianchi M, Premi E, Gadola Y, Cotelli M, Pengo M, Perrone F, Scolaro M, Archetti S, Solje E, Padovani A, Pascual-Leone A, Borroni B. Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease. Ann Neurol. 2022 Aug;92(2):322-334. doi: 10.1002/ana.26411. Epub 2022 Jun 6.
citation: Grover S, Fayzullina R, Bullard BM, Levina V, Reinhart RMG. A meta-analysis suggests that tACS improves cognition in healthy, aging, and psychiatric populations. Sci Transl Med. 2023 May 24;15(697):eabo2044. doi: 10.1126/scitranslmed.abo2044. Epub 2023 May 24.
citation: Iaccarino HF, Singer AC, Martorell AJ, Rudenko A, Gao F, Gillingham TZ, Mathys H, Seo J, Kritskiy O, Abdurrob F, Adaikkan C, Canter RG, Rueda R, Brown EN, Boyden ES, Tsai LH. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature. 2016 Dec 7;540(7632):230-235. doi: 10.1038/nature20587.
citation: Maestu F, de Haan W, Busche MA, DeFelipe J. Neuronal excitation/inhibition imbalance: core element of a translational perspective on Alzheimer pathophysiology. Ageing Res Rev. 2021 Aug;69:101372. doi: 10.1016/j.arr.2021.101372. Epub 2021 May 21.
citation: Palop JJ, Mucke L. Network abnormalities and interneuron dysfunction in Alzheimer disease. Nat Rev Neurosci. 2016 Dec;17(12):777-792. doi: 10.1038/nrn.2016.141. Epub 2016 Nov 10.