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Increasing brain gamma activity improves episodic memory and restores cholinergic dysfunction in Alzheimer’s disease

Ann Neurol. 2022 May 24. doi: 10.1002/ana.26411. Online ahead of print.

ABSTRACT

OBJECTIVE: 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).

METHODS: In 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.

RESULTS: We 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.

INTERPRETATION: Precuneus 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. This article is protected by copyright. All rights reserved.

PMID:35607946 | DOI:10.1002/ana.26411

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