Is Deep Brain Stimulation Effective in Treating Alzheimer's?

This Brain Procedure Is Often Used to Treat Parkinson's Disease

Deep brain stimulation, artwork
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It sounds like something from the makers of Star Trek, but researchers are seeing possibilities emerge with the use of deep brain stimulation for people who have mild Alzheimer's disease. And, in a world where medications are available but the benefits are limited, it's critical to continue to develop alternate therapies to treat and prevent Alzheimer's.

What Is Deep Brain Stimulation?

Deep Brain Stimulation (DBS) is a procedure where electrodes are placed inside the brain and programmed to give off small electrical pulses to stimulate brain activity.

DBS has been used for several years for people with Parkinson's disease with considerable success in reducing tremors and muscle contractions, as well as improving posture. It's also being researched to treat other medical conditions, such as depression and obsessive-compulsive disorder.

How Are Electrodes Placed in the Brain?

The short answer: brain surgery. In order for DBS to be possible, wires have to be inserted into the brain. Using local anesthesia, a neurosurgeon drills holes into the skull of the patient and carefully threads wires into different areas of the brain. (Local anesthesia, when a patient is awake but an area of the body is numbed, can be used because the brain itself cannot feel any pain.)

A pacemaker-like machine is then implanted under general anesthesia into the chest of the person where it can eventually deliver 130 miniature electrical impulses per second to the wires and, consequently, the brain.

When initially implanted, the stimulator is turned off; a few days or weeks after the surgery, the stimulator is turned on and begins to deliver the electrical impulses to the brain.

When used to treat Alzheimer's disease, those wires are typically connected to the fornix in the brain. According to Johns Hopkins Medicine, "the fornix is a brain pathway instrumental in bringing information to the hippocampus, the portion of the brain where learning begins and memories are made, and where the earliest symptoms of Alzheimer’s appear to arise."

How Does Deep Brain Stimulation Work?

There are several theories as to why it works, but there's no conclusive answer yet. In Parkinson's, it's thought to interrupt and disrupt the faulty firing of the brain.

In fact, researchers' understanding of DBS is so limited that the possibility of utilizing it for Alzheimer's was discovered accidentally when DBS was being tested on a man who was morbidly obese as a way to try to control his appetite. As they were testing him with the wire placement and electrical impulses, he reported a vivid memory. When they turned off the impulses, the memory went away, and when they turned the stimulator back on, the memory returned. This led to the realization that perhaps there is a way to stimulate the brain and the memories it holds.

Is It Safe?

DBS appears to be fairly safe. Although the thought of brain surgery sounds very risky, experts say this procedure is actually not as invasive as it sounds. There are always risks with brain surgery; however, over 100,000 people throughout the world with Parkinson's disease have undergone DBS with minimal problems. Risks include infection, equipment malfunction, stroke, battery failure, and movement of the wire.

Research on Deep Brain Stimulation and Alzheimer's Disease

Phase I Research

In 2010, the Annals of Neurology journal published research outlining a phase I clinical trial conducted in Canada with six people diagnosed with early Alzheimer's disease. They each had a deep brain stimulator surgically implanted in their brain and experienced 12 months of continuous electrical stimulation. Testing of their cognitive functioning at 6 and 12 months indicated an improvement, or a less-than-expected decline in three of the six participants.

Additionally, PET scans were used to evaluate cerebral glucose metabolism, which is the ability of the brain to break down sugars for brain fuel and can also be an indicator of the activity levels of neurons in the brain.

People with Alzheimer's typically display a decrease in glucose metabolism over time, but these six research participants showed an increase that was maintained throughout the study. Interestingly, the declining ability of the brain to break down sugar in Alzheimer's disease has caused some researchers to call Alzheimer's "type 3 diabetes."

Phase II Research

In a phase II study through Johns Hopkins, 42 patients ages 45 to 85 participated in DBS to target their Alzheimer's disease. They each underwent DBS surgery for implantation between 2012 and 2014. Half of them had their stimulators turned on after 2 weeks, and half of them had it turned on after 12 months. This was a double blind study, since neither the physicians nor the patients knew when the stimulators were activated.

Cognition was assessed in this study through multiple tests including the ADAS-Cog 13. Cerebral glucose metabolism was also measured in different areas of the brain.

The results of this study were interesting, and not necessarily what was expected. At 6 months after implantation of the stimulator, cerebral glucose metabolism had increased significantly, but those gains were not sustained at 12 months. Additionally, an age-related difference in response was noted. Those participants who were over age 65 demonstrated improvements in cognitive functioning and in cerebral glucose metabolism. Those who were under age 65 did not show significant improvements in either area. The researchers theorized that this effect may have been related to the sometimes greater brain structure deterioration in younger people with Alzheimer's (early onset Alzheimer's), as compared to those with late onset Alzheimer's.

Summary of DBS Effects on the Brain

The effects of DBS on Alzheimer's have been studied through these phase I and phase II clinical trials, but information on how it affects the brain has also been collected from its use in other settings, including other research studies and in treating Parkinson's disease. The following effects have been found:

Improved overall cognition: Research on DBS in people with Alzheimer's resulted in improved cognition for some of the participants, as measured by multiple neuropsychological tests. These tests measure several aspects of brain functioning, including memory, orientation, word recognition, and more.

Increased hippocampus volume: While the hippocampus (a part of the brain associated with memory) atrophies with the presence of aging and more significantly in Alzheimer's disease, DBS has been found to increase the volume of the hippocampus in persons with Alzheimer's. Hippocampal volume has been correlated with memory functioning.

Increased cerebral glucose metabolism: As highlighted above, some subjects who received DBS demonstrated improved glucose metabolism in multiple areas of the brain.

Increased volume of fornix and mammillary bodies: The fornix and mammillary bodies in the brain (which are both related to memory functioning) have demonstrated increased volume after DBS in those with Alzheimer's.

Higher acetylcholine levels: DBS has also been shown in research to trigger the release of acetylcholine. Acetylcholine helps transfer messages from one nerve cell to the next in our brains.

Increased spatial memory: After deep brain stimulation to the fornix of rats, they demonstrated improved spatial memory in their ability to navigate a maze. While animal studies don't always transfer to humans, they often provide us with insights about the safety and effectiveness of experimental procedures.

Decreased verbal fluency: Deep brain stimulation has been used for years in people with Parkinson's with significantly positive results. However, some research has found that verbal fluency has declined in some of these individuals. While many with Parkinson's feel that this risk is worth the benefit that deep brain stimulation provides for them. it might not so readily be deemed a worthwhile risk in those with Alzheimer's disease.

Ethical Considerations

While there have been multiple studies conducted in humans, some researchers are calling for additional and expanded studies using DBS in animals before continuing more research with people. They point out that while there have been DBS research participants who have experienced some cognitive improvement, there have also been a few others who declined in some cognitive areas after deep brain stimulation.

These researchers also highlight the fact that there's a lack of understanding as to how deep brain stimulation works; thus, they recommend that more information is acquired before expanding clinical trials with people.

A Word From Verywell

Deep brain stimulation has been well-established as an appropriate treatment for Parkinson's disease; however, more research is required to discern its benefits in Alzheimer's disease. The potential of DBS for cognitive improvement is exciting, especially as we continue to struggle to find an effective treatment for Alzheimer's.

Sources:

Fagundes, VDC, Rieder, CRM, Nunes da Cruz, A, et al, Deep Brain Stimulation Frequency of the Subthalamic Nucleus Affects Phonemic and Action Fluency in Parkinson’s Disease. Parkinson's Disease. 2016.

Hescham S, Temel Y, Schipper S. et al, Fornix deep brain stimulation induced long-term spatial memory independent of hippocampal neurogenesis. Brain Structure and Function. 2017 Mar;222(2):1069-1075.

Johns Hopkins Medicine. Johns Hopkins Surgeons Implant First Brain ‘Pacemaker’ for Alzheimer’s Disease in United States as Part of a Clinical Trial Designed to Slow Memory Loss. December 2012.

Laxton AW, Tang-Wai DF, McAndrews MP, et al. Annals of Neurology. 2010 Oct;68(4):521-34. A phase I trial of deep brain stimulation of memory circuits in Alzheimer's disease. Annals of Neurology. 2010 Oct;68(4):521-34.

Lozano AM, Fosdick L, Chakravarty MM, et al, A Phase II Study of Fornix Deep Brain Stimulation in Mild Alzheimer's Disease. Journal of Alzheimer's Disease. 2016 Sep 6;54(2):777-87.

Ovadia D, Bottini G.. Neuroethical implications of deep brain stimulation in degenerative disorders. Current Opinion in Neurology. 2015 Dec;28(6):598-603

Viana JNM, Vickers JC, Cook MJ, Gilbert F, Currents of memory: recent progress, translational challenges, and ethical considerations in fornix deep brain stimulation trials for Alzheimer's disease. Neurobiology of Aging. 2017 Aug;56:202-210.

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