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Pacemaker could help treat Alzheimer's

Pacemakers regulate the beat of a weak heart and ease the tremors caused by Parkinson's disease, and now Johns Hopkins Medicine researchers hope the devices also will slow down the symptoms of Alzheimer's.

Doctors at Hopkins and four other medical institutions will spend the next year implanting pacemakers in the brains of 40 patients with early-onset Alzheimer's as part of a clinical trial looking at whether deep electric stimulation of the brain can slow down or reverse memory and cognitive declines.


The federally funded study will build on findings by a smaller Canadian trial, in which pacemakers implanted in six Alzheimer's patients showed evidence of improving their condition. Patients in that 2010 trial showed increases in glucose metabolism, which generally declines in those with Alzheimer's.

The Hopkins surgery will involve sending electric pulses to the fornix of the brain, a curved, fibrous structure that links the hippocampus to the hypothalamus and plays a prime role in memory function.


"What we are essentially trying to do is drive the memory circuit and make it work better and more efficiently," said Dr. Paul B. Rosenberg, the study's site director. He is an associate professor of psychiatry and behavioral sciences at the Johns Hopkins University School of Medicine.

Nearly 5.4 million people in the United States, including 86,000 Marylanders, live with Alzheimer's, a type of degenerative neurological disorder that develops slowly over time. People with the disease suffer memory loss and mood swings, and may have problems performing complex tasks.

Treatment, which mainly involves drugs that reduce the buildup of plaque in between nerves in the brain, have shown limited success. The plaque formed from the protein fragment beta amyloid eventually continues to accumulate.

Drug maker Eli Lilly & Co. recently said that results from two trials testing a drug that targeted beta amyloid did not improve the cognitive ability of patients with different stages of Alzheimer's. The company also said it will conduct a new study testing the drug only on those with early onset of the disease.

Pfizer and Johnson & Johnson said earlier this year that a drug the companies developed to target beta amyloid also did not improve symptoms of Alzheimer's.

"These drugs work for some people for some time, but eventually they stop working as amyloid continues to destroy the brain," said Cass Naugle, executive director of the Alzheimer's Association Greater Maryland Chapter.

Rosenberg said the Hopkins study takes a different approach by targeting the brain mechanically.

The pacemaker sits under the shoulder blade of a patient. Narrow wires attached to the device are implanted in the brain through tiny holes drilled in the upper forehead. The pacemaker is turned up high enough for the patient to feel a little warmth and then adjusted to a certain voltage. After that the patient won't even be able to feel the device, Rosenberg said.


Half of the participants in the study will have the pacemaker turned on immediately; the others will have it turned on in a year. It could be a few years before researchers know the results, Rosenberg said. Pacemakers already have been implanted in two patients.

The study could lead to a variety of outcomes, he said. They may find the pacemaker can be used in conjunction with medicine, or the study could teach scientists new facts about the brain that could help them develop a less invasive treatment than surgery.

"It is not likely to reverse the damage that is already there, but we might be able to slow down the progression a great deal," Rosenberg said.

A growing field of research is exploring how direct stimulation of the brain can help treat certain disorders. Neural imaging has enabled scientists to see how the brain changes when attacked by disease, helping to evolve understanding of the brain.

"The advances in neuroscience are creating a whole new frontier for the study of the brain," said Dr. Ali Rezai, a neurosurgeon and director of the neuroscience program at Ohio State University's Wexner Medical Center, where scientists are studying how pacemakers in the brain can treat disease. That research is separate from the Hopkins study.

The Food and Drug Administration approved the use of pacemakers for advanced Parkinson's in 2002, and studies have found that it has helped calm the tremors and uncontrollable movements caused by the disease. Pacemakers also are used to treat epilepsy and obsessive compulsive disorder.


At Ohio State, Rezai and other scientists also are looking at how a pacemaker can affect Alzheimer's symptoms. Unlike Hopkins, scientists there are targeting a part of the brain involved in behavior and cognition rather than memory.

"This is a target that anatomically in the brain has a strong connection to memory," said Rezai, a lead investigator on the study.

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Doctors implanted a pacemaker in a patient in October and plan to use the devices on 10 patients, he said.

Investigators at Ohio State are also using pacemakers to test whether brain stimulation can help treat obesity by targeting a part of the brain linked to addiction.

There are minor risks to brain stimulation, including infection and bleeding, but it has mostly been proven safe, researchers said.

Dr. Laurie Ryan, clinical trials program director at the National Institute of Aging division of neuroscience, said pacemakers could lead to a new option for treating Alzheimer's. The institute is one of the Hopkins study's financial supporters.


"There most likely won't be a single treatment for Alzheimer's," Ryan said. "There won't be one magic bullet. This will be something in the arsenal that people can use."