Tele-supervised home-based transcranial alternating current stimulation (tACS) for Alzheimer’s disease: a pilot study

Abstract

BackgroundOver 55 million people worldwide are currently diagnosed with Alzheimer’s disease (AD) and live with debilitating episodic memory deficits. Current pharmacological treatments have limited efficacy. Recently, transcranial alternating current stimulation (tACS) has shown memory improvement in AD by normalizing high-frequency neuronal activity. Here we investigate the feasibility, safety, and preliminary effects on episodic memory of an innovative protocol where tACS is administered within the homes of older adults with AD with the help of a study companion (HB-tACS).MethodsEight participants diagnosed with AD underwent multiple consecutive sessions of high-definition HB-tACS (40 Hz, 20-min) targeting the left angular gyrus (AG), a key node of the memory network. The Acute Phase comprised 14-weeks of HB-tACS with at least five sessions per week. Three participants underwent resting state electroencephalography (EEG) before and after the 14-week Acute Phase. Subsequently, participants completed a 2–3-month Hiatus Phase not receiving HB-tACS. Finally, in the Taper phase, participants received 2–3 sessions per week over 3-months. Primary outcomes were safety, as determined by the reporting of side effects and adverse events, and feasibility, as determined by adherence and compliance with the study protocol. Primary clinical outcomes were memory and global cognition, measured with the Memory Index Score (MIS) and Montreal Cognitive Assessment (MoCA), respectively. Secondary outcome was EEG theta/gamma ratio. Results reported as mean ± SD.ResultsAll participants completed the study, with an average of 97 HB-tACS sessions completed by each participant; reporting mild side effects during 25% of sessions, moderate during 5%, and severe during 1%. Acute Phase adherence was 98 ± 6.8% and Taper phase was 125 ± 22.3% (rates over 100% indicates participants completed more than the minimum of 2/week). After the Acute Phase, all participants showed memory improvement, MIS of 7.25 ± 3.77, sustained during Hiatus 7.00 ± 4.90 and Taper 4.63 ± 2.39 Phases compared to baseline. For the three participants that underwent EEG, a decreased theta/gamma ratio in AG was observed. Conversely, participants did not show improvement in the MoCA, 1.13 ± 3.80 after the Acute Phase, and there was a modest decrease during the Hiatus −0.64 ± 3.28 and Taper −2.56 ± 5.03 Phases.ConclusionThis pilot study shows that the home-based, remotely-supervised, study companion administered, multi-channel tACS protocol for older adults with AD was feasible and safe. Further, targeting the left AG, memory in this sample was improved. These are preliminary results that warrant larger more definite trials to further elucidate tolerability and efficacy of the HB-tACS intervention. NCT04783350.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04783350?term=NCT04783350&draw=2&rank=1, identifier NCT04783350.

A Focused Review of Gamma Neuromodulation as a Therapeutic Target in Alzheimer’s Spectrum Disorders

“…Administering daily sessions of frontal gamma TACS weekly, over 2–4 weeks, was further associated with increased bilateral hippocampal perfusion and bilateral temporal gamma activity [ 77 ]; and, simultaneous administration with a memory challenge for 8 sessions over 4 weeks was associated with improved WM and verbal fluency [ 81 ]. In addition to frontal areas, gamma TACS stimulation at Pz (e.g., precuneus) and of the angular gyrus, whether a single session or daily sessions over weeks, have also been associated with improved WM and verbal fluency [ 82 ], including in comparison to sham stimulation [ 74 , 78 ].…”

Transcranial alternating current stimulation (tACS) at gamma frequency: an up-and-coming tool to modify the progression of Alzheimer’s Disease

“…In other studies ([ 122 , 123 ], clinical trial NCT04783350), researchers stimulated a specific area of the lateral parietal cortex, the left angular gyrus, in which the conscious experience of retrieving vivid, rich and multi-sensory episodic memories resides [ 124 – 126 ]. Interestingly, both groups used an HB-tACS protocol that was administered by a caregiver previously receiving a lab-based training, while the adherence was remotely supervised in real-time by physicians.…”

“…In Cappon’s group instead, despite the memory improvement in MIS, the participants only showed modest benefit in the Montreal Cognitive Assessment (MoCA) test. According to the authors, this result is likely due to the fact that the MIS evaluates both the free recall and the cued recall condition, while the MoCA only measures the delayed free recall condition and thus a larger effect can be reached by using MIS [ 123 ]. Despite the limited number of patients involved, these studies suggest that the left angular gyrus may be a suitable target area for specific spatial modulation of brain gamma oscillations to induce memory enhancement.…”