Neurostimulation devices to treat Alzheimer's disease

Abstract

The use of neurostimulation devices for the treatment of Alzheimer's disease (AD) is a growing field. In this review, we examine the mechanism of action and therapeutic indications of these neurostimulation devices in the AD process. Rapid advancements in neurostimulation technologies are providing non-pharmacological relief to patients affected by AD pathology. Neurostimulation therapies include electrical stimulation that targets the circuitry-level connection in important brain areas such as the hippocampus to induce therapeutic neuromodulation of dysfunctional neural circuitry and electromagnetic field (EMF) stimulation that targets anti-amyloid molecular pathways to promote the degradation of beta-amyloid (Aβ). These devices target specific or diffuse cortical and subcortical brain areas to modulate neuronal activity at the electrophysiological or molecular pathway level, providing therapeutic effects for AD. This review attempts to determine the most effective and safe neurostimulation device for AD and provides an overview of potential and current clinical indications. Several EMF devices have shown a beneficial or harmful effect in cell cultures and animal models but not in AD human studies. These contradictory results may be related to the stimulation parameters of these devices, such as frequency, penetration depth, power deposition measured by specific absorption rate, time of exposure, type of cell, and tissue dielectric properties. Based on this, determining the optimal stimulation parameters for EMF devices in AD and understanding their mechanism of action is essential to promote their clinical application, our review suggests that repeated EMF stimulation (REMFS) is the most appropriate device for human AD treatments. Before its clinical application, it is necessary to consider the complicated and interconnected genetic and epigenetic effects of REMFS-biological system interaction. This will move forward the urgently needed therapy of EMF in human AD.

Keywords: Alzheimer’s disease; clinical; devices; electromagnetic fields stimulation; preclinical; review; treatment.

Figure 1.. Previous REMFS experiment workflow and apparatus.

(A) Culturing cells in a tri-gas incubator, alternating with treatments in a TEM chamber. After final treatments, cells were processed, and extracts were used for analysis. (B) Source of the EMF (function generator). The signal is then sent to an amplifier, then to the TEM chamber. The signal is monitored through the TEM chamber with an oscilloscope. (C) Front view photograph of a compact and convenient equipment system. (D) Rear view of the compact cart setup. (E) A side view of the TEM chamber shows a shelf across the middle for cell cultures. ELISA: enzyme-linked immunosorbent assay; EMF: electromagnetic field; LDH: lactate dehydrogenase; REMFS: repeated electromagnetic field stimulation; TEM: transverse electromagnetic. Reprinted from [75] (CC BY 4.0)

Figure 2.. Perspective view of an REMFS with a head-mounted antenna, including control system and coupling unit.

REMFS: repeated electromagnetic field stimulation. Modified with permission from “Electromagnetic Frequency Generation System and Method” by Perez, et.al. 2022. Copyright 2022 by Dr. Perez and Dr. Rizkalla (U.S. Patent Pending)

Figure 3.. REMFS birdcage coil.

The proposed REMFS birdcage coil in high-pass configuration includes 16 meander line coils and 32 tuning capacitors, with eight ports positioned at a 45° displacement from each other. REMFS: repeated electromagnetic field stimulation