Patient-Tailored, Home-Based Non-invasive Brain Stimulation for Memory Deficits in Dementia Due to Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is an irreversible, progressive brain disorder that can cause dementia (Alzheimer's disease-related dementia, ADRD) with growing cognitive disability and vast physical, emotional, and financial pressures not only on the patients but also on caregivers and families. Loss of memory is an early and very debilitating symptom in AD patients and a relevant predictor of disease progression. Data from rodents, as well as human studies, suggest that dysregulation of specific brain oscillations, particularly in the hippocampus, is linked to memory deficits. Animal and human studies demonstrate that non-invasive brain stimulation (NIBS) in the form of transcranial alternating current stimulation (tACS) allows to reliably and safely interact with ongoing oscillatory patterns in the brain in specific frequencies. We developed a protocol for patient-tailored home-based tACS with an instruction program to train a caregiver to deliver daily sessions of tACS that can be remotely monitored by the study team. We provide a discussion of the neurobiological rationale to modulate oscillations and a description of the study protocol. Data of two patients with ADRD who have completed this protocol illustrate the feasibility of the approach and provide pilot evidence on the safety of the remotely-monitored, caregiver-administered, home-based tACS intervention. These findings encourage the pursuit of a large, adequately powered, randomized controlled trial of home-based tACS for memory dysfunction in ADRD.

Remotely Monitored Home-Based Neuromodulation With Transcranial Alternating Current Stimulation (tACS) for Mal de Débarquement Syndrome

“…Side effects were similar to those reported in tDCS and tACS studies and generally did not last past the duration of stimulation sessions ( 23 ). This is with the caveat that the majority of human NIBS studies stay within 1–2 mA ranges of stimulation intensity, corresponding to a current density of <0.15 mA/cm2 ( 25 ). In this study, the in-phase stimulation was administered at 4 mA split into two electrodes, yielding a maximum current density of 0.02 mA.…”

“…The 70 sessions performed over 14-weeks were administered by a spouse with excellent tolerability and adherence. Improvement was assessed on the non-visual Montreal Cognitive Assessment ( 25 ). Though current shunting through the cerebrospinal fluid can present a problem when electrodes are placed at a distance on the scalp, focal stimulation using a 4 × 1 montage with placement informed by electrical field modeling as in this study may be able to address shunting issues.…”

Working Memory and Transcranial-Alternating Current Stimulation—State of the Art: Findings, Missing, and Challenges

“…Results from this study suggest that both participants’ cognitive abilities improved from baseline on tests administered every 2 weeks during the 14 weeks of the study and that the overall protocol is safe and feasible. The results of the study provide an incentive for future randomized-controlled trials with large sample sizes to investigate the effect of tACS in a real-world setting ( Bréchet et al, 2021 ). The details of the study are summarized in Table 2 .…”

“…Whereas multiple sessions of gamma-tACS administered over several days produced positive cognitive results ( Haller et al, 2020a ). In patients with cognitive impairment and dementia (four studies), all studies investigating the effect of gamma-tACS delivered over the DLPFC or left angular gyrus showed an improvement in cognitive outcome from either single or multiple stimulation sessions, and the effect persisted for 1 month when multiple gamma-tACS sessions were applied over the DLPFC (30 min/day–5 days/week for 4 weeks) and combined with cognitive exercises ( Kehler et al, 2020 ; Bréchet et al, 2021 ; Kim et al, 2021 ; Moussavi et al, 2021 ). In addition, the application of gamma-tACS over the prefrontal cortex for 10 days improved WM in patients with MDD (1 study) ( Haller et al, 2020b ).…”

“…Interestingly, Bréchet et al (2021) investigated the feasibility, efficacy, and safety of patient-tailored, home-based gamma-tACS delivered over the left angular gyrus and administered over 14 weeks (70 sessions in total) in two patients with Alzheimer’s disease-related dementia. In this study tACS sessions were delivered by trained caregivers and the administration can be remotely monitored by the study team.…”