While there is no cure for Alzheimer’s disease, there are several prescription medicines available to manage its symptoms. However, most of these symptomatic treatments become ineffective over time as the disease progresses.
Several experimental therapies — including two non-drug treatments — currently are under investigation, all aiming to delay Alzheimer’s progression or reduce the symptoms of the disease. Two of the investigational treatments, specifically deep brain stimulation (DBS) and repetitive transcranial magnetic stimulation (rTMS), work to improve neuronal signaling in the brain.
Researchers are investigating whether these non-drug therapies can treat some of the memory, thinking and behavior problems caused by Alzheimer’s, an irreversible and progressive disease. Alzheimer’s is characterized by abnormal deposits of proteins in the brain, especially in regions involved in memory and thinking. These protein deposits disrupt the connection between nerve cells, eventually resulting in their death.
Deep brain stimulation
Deep brain stimulation, or DBS, is a well-established method for treating mobility issues in people with Parkinson’s disease. It now is being investigated for the treatment of Alzheimer’s.
In DBS, electrical impulses are delivered to parts of the brain that are not functioning optimally. Electrodes are surgically implanted into the brain. These electrodes are connected to a small battery-powered stimulator, which is itself implanted under the collarbone. The stimulator delivers electric impulses to the electrodes via a wire placed beneath the skin that runs along the neck and behind the ear.
For Alzheimer’s patients, DBS is often targeted at a brain area called the fornix, which is a major inflow and output pathway in the brain’s memory circuit. The fornix is one of the first areas of the brain that is affected in Alzheimer’s disease. Researchers hope that DBS can help drive critical neural activity in this region of the brain, and help maintain memory and other neural functions.
Phase 1 studies have shown that DBS is safe and well-tolerated. In people with early or mild Alzheimer’s disease, DBS has been found to improve memory, reduce cognitive decline, reverse changes in glucose metabolism in the brain, and increase hippocampus volume.
Two clinical trials are underway in Spain (NCT03290274) and China (NCT03352739) to evaluate the safety and efficacy of DBS in Alzheimer’s patients.
Another 12-month, multi-center, double-blind, randomized clinical trial (NCT03622905) is recruiting around 210 participants with mild Alzheimer’s disease to also evaluate the safety and efficacy of DBS. That study is expected to be completed in October of 2020.
Repetitive transcranial magnetic stimulation
Repetitive transcranial magnetic stimulation, or rTMS, is a noninvasive treatment approved by the U.S. Food and Drug Administration (FDA) for treating clinical depression. It now is also being investigated as a potential therapy for Alzheimer’s disease.
rTMS is a non-invasive procedure in which an electromagnetic coil is placed over the forehead. Repeated magnetic impulses are then delivered to stimulate nerve cells in specific regions of the brain.
Early investigations have shown that rTMS is well-tolerated and safe. They’ve also shown that patients with mild cognitive impairment and mild Alzheimer’s disease show significant improvements in cognition compared with people with severe Alzheimer’s disease. These differences are most likely due to brain damage in patients with severe Alzheimer’s disease, though it also is possible that the correct area of the brain is not being targeted. One limitation of traditional rTMS is that it cannot effectively target deep brain regions. This may be remedied by using deep rTMS coils. However, these have not been well-studied so far.
Two Phase 4 clinical trials evaluating rTMS are underway in the U.S. (NCT02190084) and Canada (NCT02537496). These studies aim to determine the treatment’s effectiveness in improving symptoms of apathy, specifically a lack of interest or enthusiasm, and poor memory in people with mild Alzheimer’s disease.
Last updated: Oct. 15, 2019
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