Objective This study aimed to assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (gamma-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 gamma-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 gamma-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 gamma-tACS but not after sham tACS. Face-name associations scores improved with gamma-tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after gamma-tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to gamma-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 gamma-tACS, able to increase gamma-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 gamma-tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022

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

Grassi M.;
2022-01-01

Abstract

Objective This study aimed to assess whether non-invasive brain stimulation with transcranial alternating current stimulation at gamma-frequency (gamma-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 gamma-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 gamma-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 gamma-tACS but not after sham tACS. Face-name associations scores improved with gamma-tACS (p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission, increased only after gamma-tACS (p < 0.001). ApoE genotype and baseline cognitive impairment were the best predictors of response to gamma-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 gamma-tACS, able to increase gamma-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 gamma-tACS was dependent on genetic factors and disease stage. ANN NEUROL 2022
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1477526
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