Friday, March 11, 2011

Deep brain stimulation technique to fight Alzheimer’s

Insertion of a deep brain stimulator (DBS), a device similar to a pacemaker for the brain, may improve memory and function for patients with Alzheimer’s disease.  The National Institute of Neurological Disorders and Stroke (NINDS) explains that the set up for deep brain stimulation involves three parts: an electrode; a neurostimulator, which is the battery pack; and the extension. The surgeon implants the electrode in a specific region of the brain, which he or she identifies using an imaging scan, such as a magnetic resonance imaging (MRI) scan or computed tomography (CT) scan. With the neurostimulator, the surgeon implants that near the collarbone, then connects the two parts with the extension, which is also underneath the skin. The electrical signals are sent from the neurostimulator through the extension and up through the electrode to the brain.

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Recent research showed that after implanting a DBS in six patients with Alzheimer’s, half of the patients had either improved memory, or a slower rate of decline.

“We showed that not only is this a safe procedure, but that the evidence is there to warrant a bigger trial,” according to Dr. Andres Lozano and colleagues at Toronto Western Hospital, who conducted the research. “Any amount of time that extends quality of life and quality years to someone with Alzheimer’s may be a benefit.”

Alzheimer’s disease (AD) is the most common form of dementia among older people, and affects more than five million Americans, according to the Alzheimer’s Organization. 

“Alzheimer’s disease (AD) is characterized by functional impairment in the neural elements and circuits underlying cognitive and memory functions,” according to Lozano. Initially, affected individuals have mild memory problems, which progress over time, to the point of needing total care.  Other, later symptoms can include anxiety, wandering, and aggression.  No treatment can stop the disease. However, some drugs, may delay the progression of the disease, and others, including antipsychotics, may help treat certain symptoms for a limited time.

Lozano and his team investigated the theory that electrical stimulation of structures deep in the brain, including the hypothalamus, might improve symptoms by enrolling six willing participants with early signs of Alzheimer’s in their study.

Each patient left the hospital within three days after the study and continued their standard medical therapy for Alzheimer’s disease, as well as continuous stimulation from the implanted device for one year.

During that time, the subjects were assessed in several ways, including cognitive testing, brain mapping, and imaging.  Their cognitive function was evaluated by several different types of measurement scales. Positive emission tomography (PET) scans, a type of brain scan that measures metabolic activity, were used to assess the way the DBS device changed glucose metabolism in the brain.  (Alzheimer’s disease can alter how glucose is used in the brain.) 

In half of the patients, by six or 12 months, their cognitive function had either improved or had declined at a slower rate than expected.  “Evaluation of the Alzheimer’s Disease Assessment Scale cognitive subscale and the Mini Mental State Examination suggested possible improvements and/or slowing in the rate of cognitive decline at 6 and 12 months in some patients,” according to the researchers.

In addition, the PET scans showed that the abnormal glucose metabolism typically seen in patients with Alzheimer’s disease improved after insertion of the DPS device, and the improvement continued throughout the year of follow-up.

None of the patients had any serious side effects during the year after the device was implanted.

Although Lozano’s  study is small, the results are encouraging. Future, larger studies may provide more information on a potentially effective therapy for treating Alzheimer’s disease, or slowing the decline, which could complement additional therapies.

“There is an urgent need for novel therapeutic approaches for Alzheimer’s disease. Modulating pathological brain activity in this illness with DBS merits further investigation.”

“It’s a very intriguing study,” says Laurie Ryan, program director of Alzheimer’s disease clinical trials at the National Institute on Aging, who was not involved in the research. “I don’t think we can predict how it will turn out with a larger number of subjects, but they did have some very interesting data, particularly the PET data [on glucose metabolism]."

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Although Lozano is careful to stress that deep brain stimulation is a potential therapy, aiming to improve symptoms of Alzheimer’s without necessarily tackling the underlying cause, he does feel that it opens up a new way of looking at the disease. “We should think of Alzheimer’s as a brain circuit disorder,” he says. This is in keeping with some of the research being done on the effects of normal aging on brain circuits, says Ryan. “I think this is another piece of the puzzle that is pointing us in that direction.” Lozano and his colleagues now plan to undertake a larger, Phase II, clinical trial.

Patients with milder forms of Alzheimer's seemed to benefit the most from the deep brain stimulation.

The procedure seems to work by driving the activity in less-damaged areas of the brain, "reactivating these brain circuits that are responsible and cognitive functioning," Lozano explained.

However, the deep brain stimulation is an invasive technique. "This is not a procedure free of risk," noted Dr. Richard Lipton, an attending neurologist at Montefiore Medical Center in New York City. "It involves taking often frail, older adults and drilling a hole through the skull, then pressing a needle through the tissue of the brain till the tip gets into a crucial area where you want to leave it. If you go through a blood vessel, you can produce bleeding that can cause serious harm. This is not a benign procedure. So, the device would have to be approved before it is available for widespread use."

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Dr. Lozano first discovered the potential for DBS to treat Alzheimer's disease while treating a patient for obesity using DBS back in 2003. While signaling areas of the brain, Dr. Lozano and his team triggered memories in the patient. In follow-up testing the patient's memory improved and Dr. Lozano set in motion the first ever DBS trial of patients with early signs of Alzheimer's disease.

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