Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer’s disease

Abstract

Background Alzheimer’s disease (AD) is associated with alterations in cortical perfusion that correlate with cognitive impairment. Recently, neural activity in the gamma band has been identified as a driver of arteriolar vasomotion while, on the other hand, gamma activity induction on preclinical models of AD has been shown to promote protein clearance and cognitive protection. Methods In two open-label studies, we assessed the possibility to modulate cerebral perfusion in 15 mild to moderate AD participants via 40Hz (gamma) transcranial alternating current stimulation (tACS) administered 1 h daily for 2 or 4 weeks, primarily targeting the temporal lobe. Perfusion-sensitive MRI scans were acquired at baseline and right after the intervention, along with electrophysiological recording and cognitive assessments. Results No serious adverse effects were reported by any of the participants. Arterial spin labeling MRI revealed a significant increase in blood perfusion in the bilateral temporal lobes after the tACS treatment. Moreover, perfusion changes displayed a positive correlation with changes in episodic memory and spectral power changes in the gamma band. Conclusions Results suggest 40Hz tACS should be further investigated in larger placebo-controlled trials as a safe, non-invasive countermeasure to increase fast brain oscillatory activity and increase perfusion in critical brain areas in AD patients. Trial registration Studies were registered separately on ClinicalTrials.gov (NCT03290326, registered on September 21, 2017; NCT03412604, registered on January 26, 2018).

The Beneficial Effects of Combining Anti-Aβ Antibody NP106 and Curcumin Analog TML-6 on the Treatment of Alzheimer’s Disease in APP/PS1 Mice

“…Increasing attention has been paid to some nonpharmacological interventions, such as noninvasive brain stimulation (NIBS), as potential alternatives to treat AD-related cognitive impairment [ 45 , 46 , 47 , 48 , 49 , 50 ]. In fact, NIBS techniques, such as transcranial electrical stimulation (tES) or repetitive transcranial magnetic stimulation (TMS), have been investigated for AD therapy [ 51 , 52 ], and perhaps, in the future, these novel treatment techniques could be applied to facilitate the effectiveness of pharmacological regimens.…”

Intensity-Dependent Gamma Electrical Stimulation Regulates Microglial Activation, Reduces Beta-Amyloid Load, and Facilitates Memory in a Mouse Model of Alzheimer's Disease

“…Thus, GES appears to exhibit similar e cacy as the other forms of gamma stimulation. Moreover, these results provide key mechanistic insights as to why GES has exhibited initial e cacy in human trials [17][18][19][20].…”

“…Electrical stimulation has been widely claimed to modulate brain function in humans [15,16]. Most excitingly, GES in humans has recently been shown to signi cantly improve memory performances, along with restoration of intracortical connectivity measures of cholinergic neurotransmission, increased cortical blood perfusion, and possible reductions of tau [17][18][19][20]. Yet, the mechanisms of action rely on animal studies utilizing other forms of gamma stimulation.…”

Local and Distributed fMRI Changes Induced by 40 Hz Gamma tACS of the Bilateral Dorsolateral Prefrontal Cortex: A Pilot Study

“…In particular, animal studies have revealed that the induction of γ frequency activity through sensory stimulation or optogenetics reduces amyloid- β plaques [ 78 , 79 ], as well as that optogenetic modulation of parvalbulmin (PV+) and somatostatin (SST+) interneurons restores γ oscillations in murine models of AD [ 80 ]. Preliminary evidences are also arising from pilot studies using 40 Hz tACS in AD patients [ 81 , 82 ].…”