Abstract
ObjectiveTo assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at γ frequency (γ-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). MethodsIn this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to γ-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-γ-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-γ-tACS or sham tACS were evaluated. ResultsTwenty MCI-AD participants completed the study. No tACS-related side effects were observed, and the intervention was well tolerated in all participants. We observed a significant improvement at the Rey auditory verbal learning (RAVL) test total recall (5.7 [95% CI, 4.0 to 7.4], p < 0.001) and long delayed recall scores (1.3 [95% CI, 0.4 to 2.1], p = 0.007) after γ-tACS but not after sham tACS. Face-name associations scores improved during γ−tACS (4.3 [95% CI, 2.8 to 5.8], p < 0.001) but not after sham tACS. Short latency afferent inhibition, an indirect measure of cholinergic transmission evaluated with TMS, increased only after γ-tACS (0.31 [95% CI, 0.24 to 0.38], p < 0.001) but not after sham tACS. Conclusionsexposure to γ-tACS over Pz showed a significant improvement of memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, compared to sham tACS.
Highlights
Alzheimer’s disease (AD) accounts for the vast majority of agerelated dementias and it is estimated that approximately 100million people worldwide will have AD dementia in 2050 [1]
Participants who were already on a pharmacologic regimen were allowed to receive treatment provided that the regimen remained unchanged for six weeks prior to the intervention, but initiation of drugs after the start of the observation period was not allowed (4 participants were on donepezil 10 mg QD, 2 participants were on zolpidem 10 mg QD, 1 patient was on trazodone 25 mg QD, 1 patient was on lorazepam 2.5 mg QD)
Double-blind, placebo-controlled, crossover study, we observed that exposure to g-transcranial alternating current stimulation (tACS) over Pz improves episodic memory performances and is associated with a restoration of short-latency afferent inhibition (SAI), an indirect marker of cholinergic transmission, in participants with mild cognitive impairment (MCI)-AD, compared to sham stimulation. g-tACS
Summary
To assess whether exposure to non-invasive brain stimulation with transcranial alternating current stimulation at g frequency (g-tACS) applied over Pz (an area overlying the medial parietal cortex and the precuneus) can improve memory and modulate cholinergic transmission in mild cognitive impairment due to Alzheimer’s disease (MCI-AD). Methods: In this randomized, double-blind, sham controlled, crossover pilot study, participants were assigned to a single 60 min treatment with exposure to g-tACS over Pz or sham tACS. Each subject underwent a clinical evaluation including assessment of episodic memory pre- and post-g-tACS or sham stimulation. Indirect measures of cholinergic transmission evaluated using transcranial magnetic stimulation (TMS) pre- and post-g-tACS or sham tACS were evaluated
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