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A Brain Pacemaker for Alzheimer’s Disease?

As many of you know, Alzheimer’s is an absolutely devastating neurodegenerative disease. It destroys the lives of loved ones with the disease, takes a terrible toll on family and friends who care for them, and costs, for patient care alone, an estimated $200 billion a year.

Illustration of a device implanted near the heart and a wire that leads to the brain.

The implanted wires stimulate the fornix, one of the first regions destroyed by Alzheimer’s. Credit: Functional Neuromodulation

Alzheimer’s is the most common form of dementia, robbing those it affects of their memory, their ability to learn and think, and their personality. It worsens over time. People forget recent events, and gradually lose the ability to manage their daily lives and care for themselves. It currently affects an estimated 5.1 million Americans; this number is expected to rise to somewhere between 11 and 16 million by 2050 unless treatments can be found in the meantime.

There’s no cure for Alzheimer’s disease (AD), but biomedical researchers are testing new drugs and biochemical approaches, treatments that could stem and possibly reverse the course of the disease. They are also exploring how conditions like obesity and diabetes—which are at epidemic levels in the U.S. and worldwide—play a role. I want to tell you about a new NIH-funded experimental approach that was tried for the first time in the U.S. in November.

Neurosurgeons at Johns Hopkins Hospital, in Baltimore, MD, implanted a ‘pacemaker’ in the brain of a patient with mild AD. You are probably familiar with the concept of a pacemaker that stabilizes heart rhythms. The implanted device sends electrical pulses to the heart muscle, resetting a normal heartbeat. In some ways, this pacemaker for AD is similar. It, too, sends electrical pulses, but targets a region of the brain called the fornix—a bundle of 1.2 million axons that normally serves as a superhighway for learning, emotion, and forming memories. The fornix is one of the first regions to be destroyed by Alzheimer’s.

To implant the pacemaker, surgeons drill two small holes in the skull and implant two ultrathin wires into the fornix on both sides of the brain. The wires are then connected to a matchbox-size control device that is inserted beneath the collarbone. After surgery, the device is completely invisible. The wires deliver 130 pulses every second. These pulses, also called deep brain stimulation, deliver just four to eight volts of electricity, so tiny a charge that the patients are completely unaware of them. The hypothesis is that these pulses will kick start and drive the ailing neurons, making them function more effectively.

The current trial is taking place at five locations—four in the U.S. and one in Canada—and will include 40 patients. Half of these will have the ‘pacemaker’ or stimulators activated two weeks after surgery while the others will have the device turned on after one year.

The current trial (called the ADvance Study) was inspired by an experiment done in Canada about five years ago in which stimulating the hypothalamus and fornix caused a surprising improvement in memory [1]. This was followed in 2010 by a small Canadian trial of six patients with mild AD. When the researchers looked at the brains of these patients, they saw increased glucose metabolism in the temporal and parietal lobes of the brain over a 13-month period—a sign of healthy functioning neurons [2]. Typically, in Alzheimer’s patients, glucose metabolism in the brain decreases as the disease progresses—so the bump in metabolism is promising.

Like any surgical procedure, there is the risk of infection, and the surgery can cause minor bleeding in the brain. But the risks are small, and while mechanically stimulating the brain to improve cognitive function is new for Alzheimer’s disease, similar hardware and surgery have been used to treat 80,000 patients with Parkinson’s disease—another progressive neurodegenerative condition. Brain stimulation is also used for depression.

This is not a cure, but if successful it might delay the steady advance of memory loss that otherwise characterizes Alzheimer’s disease.

REFERENCES:

[1] Memory enhancement induced by hypothalamic/fornix deep brain stimulation. Hamani C et al. Ann Neurol. 2008 Jan;63(1):119-23.

[2] A phase I trial of deep brain stimulation of memory circuits in Alzheimer’s disease. Laxton AW et al. Ann Neurol. 2010 Oct;68(4):521-34

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