TY - JOUR
T1 - Increasing Brain Gamma Activity Improves Episodic Memory and Restores Cholinergic Dysfunction in Alzheimer's Disease
AU - Benussi, Alberto
AU - Cantoni, Valentina
AU - Grassi, Mario
AU - Brechet, Lucie
AU - Michel, Christoph M.
AU - Datta, Abhishek
AU - Thomas, Chris
AU - Gazzina, Stefano
AU - Cotelli, Maria Sofia
AU - Bianchi, Marta
AU - Premi, Enrico
AU - Gadola, Yasmine
AU - Cotelli, Maria
AU - Pengo, Marta
AU - Perrone, Federica
AU - Scolaro, Maria
AU - Archetti, Silvana
AU - Solje, Eino
AU - Padovani, Alessandro
AU - Pascual-Leone, Alvaro
AU - Borroni, Barbara
PY - 2022
Y1 - 2022
N2 - Objective: This 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). 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. ANN NEUROL 2022;92:322–334.
AB - Objective: This 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). 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. ANN NEUROL 2022;92:322–334.
KW - Alzheimer disease
KW - Gamma
KW - Episodic memory
KW - Cholinergic dysfunction
KW - Alzheimer disease
KW - Gamma
KW - Episodic memory
KW - Cholinergic dysfunction
UR - http://hdl.handle.net/10807/227857
U2 - 10.1002/ana.26411
DO - 10.1002/ana.26411
M3 - Article
SN - 0364-5134
VL - 92
SP - 322
EP - 334
JO - Annals of Neurology
JF - Annals of Neurology
ER -