Alzheimer’s disease: Deep brain stimulation may help improve symptoms

DBS is a surgical procedure where a doctor places electrodes on a specific area of a person’s brain. The electrodes in the brain connect to wires to an electric generator — similar to a heart pacemaker — implanted under a person’s collarbone.

The electrodes create electric pulses that interrupt abnormal signals the brain may receive, causing symptoms of a disease such as tremors or movement difficulties.

“DBS disrupts information flow in the brain at the specific site of stimulation,” Dr. Andreas Horn, Ph.D., associate professor for neurology and director of Deep Brain Stimulation Research at the Center for Brain Circuit Therapeutics in the department of neurology at Brigham & Women’s Hospital in Massachusetts and lead author of the study explained to Medical News Today.

“While this sounds negative, we usually target circuits that have become derailed and carry noisy or nonsensical information,” he said.

Dr. Horn added that DBS is best understood in Parkinson’s disease, “where a noise signature in a specific frequency band can be observed in a specific circuit in the brain.”

He explained that the degree of noise corresponds to the severity of symptoms such as bradykinesia (stiffness in the body).

“By lesioning this circuit, we can tune the noise signature down, and symptoms improve. In fact, lesioning the same sites that we ‘stimulate’ with DBS leads to similar improvements [in] symptoms. DBS has a similar effect — it tunes down the aberrant ‘noise’ in specific circuits in the brain. I believe that this way, other circuits are less distracted by the noise in the affected circuit, and meaningful information will not be hindered as much to flow through these circuits.”

– Dr. Andreas Horn, lead study author

The new research began with an observation made during a Canadian study examining the use of DBS to treat obesity.

Researchers found DBS caused flashbacks of childhood memories in some study participants. Scientists then considered stimulation of this exact location in the fornix area of the brain might also help treat Alzheimer’s.

The fornix contains the white matter of the brain. Previous research links neurodegeneration of the fornix to Alzheimer’s disease.

Previous studies have also examined the use of DBS to stimulate the brain’s fornix for treating dementia.

The present study furthered the research by analyzing data from electrodes implanted in the same area of the fornix in 46 people with mild Alzheimer’s disease.

Upon analysis, researchers reported most patients did not show improvement in their symptoms. However, some participants “benefited considerably” from the treatment. These subjects had a specific circuit in the brain stimulated and demonstrated cognitive improvements after treatment.

According to Dr. Horn — who is also the head of the Movement Disorder and Neuromodulation Unit in the Department of Neurology at Charité – Universitätsmedizin Berlin — the aim of this retrospective study is to investigate what are the differences between participants in which the treatment worked better than in others.

“We could demonstrate that electrodes were placed differently in the top-responding participants — namely, in cases in which a specific bundle in the brain was modulated, the treatment had the strongest effects,” he said.

This, Dr. Horn added, is key to understanding that DBS treatment is not the exact same procedure for all diseases.

“It is a focal stimulation that needs to be targeted to a specific brain structure in each disease. For instance, while in Parkinson’s, we often target the so-called subthalamic nucleus, in tremor, a specific nucleus in the thalamus is the most used target. Since the target is key, a suitable target needs to be defined to test this treatment in novel diseases. While theoretically these targets could be informed from animal research, the past shows us that most often they instead were discovered by serendipitous events in humans.”

– Dr. Andreas Horn, lead study author

Personalized targeting is where the field is going, according to Dr. Jean-Philippe Langevin, a neurosurgeon and director of the Restorative Neurosurgery and Deep Brain Stimulation Program for Pacific Neuroscience Institute at Providence Saint John’s Health Center in Santa Monica, CA.

“In the past, it used to be that to place the electrodes inside the brain, you just looked at the gross anatomy of the brain on scans and placed an electrode in the intended target,” Dr. Langevin explained.

“But with these types of research — where they’re looking at how the fibers are traveling for each patient, should lead to personalization where the electrode is going to be placed inside the brain. You can look more precisely at the specific fibers and then select exactly for that patient where the electrode should be.”

Dr. Langevin added that personalized treatment that includes DBS could lead to improved outcomes.

“It’s going to expand our knowledge of the brain and hopefully new therapeutic options like in the case of Alzheimer’s,” he said.

DBS is already being used to treat neurological conditions like Parkinson’s, so what’s been keeping it from treating Alzheimer’s?

According to Dr. Langevin, there are two main reasons why DBS may not be widely accepted as a potential Alzheimer’s treatment. First, it is surgery, so it is viewed as a more invasive and high risk procedure compared to other treatments.

“Over time, we’ve been working on making the surgery more minimally invasive, so smaller incisions (and) less time to recovery,” he said.

The second issue is that DBS includes an implantable device that requires some adjustments, and sometimes practitioners do not feel comfortable using the programming devices, Dr. Langevin added.

Now, manufacturers have been improving the software and device programmers, making them more intuitive and easier to use, he noted.

As improvements continue in the area of DBS, it still may be a while before the treatment become available for Alzheimer’s.

“The ADvance II trial is currently running in multiple centers worldwide,” Dr. Horn noted.

“If successful, it is my understanding that it would make an FDA approval and CE mark for the procedure very likely. And, in turn, this could make the treatment available to many patients that fit the criteria for which researchers have found DBS to be helpful.”

Still, Dr. Horn emphasized that DBS is not a curative treatment option for neurodegenerative diseases such as Parkinson’s or Alzheimer’s.

“Unfortunately, the disease will progress, and the treatment will be symptomatic, i.e., at best, help improve some of the symptoms for some time,” he explained.

“In Parkinson’s disease, we have good evidence that this can lead to substantially prolonged periods with improved quality of life.”