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May/June 2013
DBS to Treat Alzheimer’s Patients?By Mike Bassett Deep brain stimulation (DBS)—a neurological treatment in which mild electrical signals are used to stimulate certain areas of the brain—has been around for decades. First approved by the FDA in 1997 as a treatment for essential tremor and later for Parkinson’s disease and dystonia, it’s also been used to treat individuals with disorders such as Tourette syndrome, epilepsy, and obsessive-compulsive disorder. Now DBS is being tested as a treatment for Alzheimer’s disease, the most common form of dementia afflicting older Americans. A two-year multicenter clinical trial is taking place at Johns Hopkins University, the University of Toronto, the University of Pennsylvania, the University of Florida, and Banner Health System in Phoenix, where researchers are examining whether DBS can be used as a means to reverse cognitive decline and boost memory. “We are limited in our symptomatic therapy [for treating Alzheimer’s] at the moment,” says Michael Okun, MD, codirector of the University of Florida’s Center for Movement Disorders and Neurorestoration, one of the sites involved in the trial. “My hope is that if this therapy works, it will provide some measureable and meaningful improvement in quality of life for individual patients who suffer from Alzheimer’s disease.” The decision to start testing whether DBS could be used to treat Alzheimer’s came about by accident when Andres Lozano, MD, PhD, FRCSC, FRSC, FCAHS, a professor and the chairman of the neurosurgery department at the University of Toronto, used DBS to treat a man who was obese. While attempting to tickle the hypothalamus, which affects hunger and eating, Lozano accidentally stimulated the fornix, a key structure in the brain for memory. “When he turned on [the DBS device], the patient had a memory flashback,” Okun says. “And when he went a little higher, the patient started seeing things in black and white and then in color. And when he turned it off, it went away. It was completely reproducible.” Lozano followed up the experience with a trial involving a small number of patients with mild Alzheimer’s disease, in which after one year of stimulation, it was determined that the hippocampus region—the brain’s memory hub—actually grew in several patients rather than shrinking. The trial also showed that some patients’ Alzheimer’s symptoms improved. What’s Involved? The electrodes are attached to the fornix on either side of the brain. “It’s the part we consider to be the superhighway of the brain—the part that connects memory centers to other parts of the brain,” Burke says. Why has DBS worked in treating some neurological disorders? “The short answer is we don’t know,” Okun says. There have been suggestions that DBS inhibited or jammed brain circuits, and that this produced therapeutic benefits, he explains, or that it excited the axons, or nerve fibers that carry information from nerve cells to other cells in the body. Now researchers believe DBS’ mechanism of action is more complicated, according to Okun. “It’s multifaceted. But ultimately it leads to an entire networkwide change in cortical regions, and in regions underneath the cortex,” he says. The individuals involved in the current trial have mild Alzheimer’s disease or dementia and are in good general health with no serious comorbidities. “They’re people who are just starting to see function deficits appear,” Burke says. “They’re just starting to have difficulty managing their finances or medications.” Good health is not the only determinant of trial participation, however. “They are well supported,” Burke adds. “They have to have care partners during the course of the study, so there needs to be family involvement.” Targeting individuals with early dysfunction makes sense, says Okun, since there’s potential for improvement in this group as opposed to individuals with more severe dysfunction. “This is a progressive degenerative disorder, so if you’re going to affect the brain circuitry and sort of restore the circuits and improve some clinical function like memory, the more substrate they have left in that circuit to modulate, the better chance there is of improving the circuit.” For purposes of the trial, one-half of the subjects will have their devices turned on two weeks after surgery, while the remaining devices will be turned on after one year. Over the course of the study, the subjects will undergo cognitive testing to assess their memory and language abilities as well as their ability to carry out simple tasks. In addition, the subjects will undergo regular monitoring through functional MRI to see whether the targeted parts of the brain actually are being stimulated. After one year, says Okun, the researchers will compare the data and see whether individuals with an operational device have improved compared with subjects whose devices were not turned on. “We want to be very careful and do this in a very controlled way to make sure we’re not fooling ourselves and to make sure we’re actually seeing changes,” Okun says, adding that assessing changes in cognition will be a little trickier than seeing whether a device stops a person from having tremors. “It’s harder to measure, and it’s going to take longer to evaluate and needs a more careful approach to make sure that what we’re doing is actually changing these features in this group of patients.” So the researchers are cautious yet hopeful. “Right now there are no good alternatives,” Burke says. “Obviously [deep brain stimulation] is not going to be easy to use in the general population, but what we’ve been able to do with medications is quite limited. So if this is found to be effective, it could be a good option for some Alzheimer’s patients.” — Mike Bassett is a freelance writer based in Holliston, Massachusetts.
Ohio State Implants Brain Pacemaker to Treat Alzheimer’s She is the first of up to 10 patients who will be enrolled in an FDA-approved study to determine whether using a brain pacemaker can improve cognitive and behavioral functioning in patients with Alzheimer’s disease. The study employs the use of deep brain stimulation (DBS), the same technology used to successfully treat about 100,000 patients worldwide with movement disorders such as Parkinson’s disease. In the study, researchers hope to determine whether DBS surgery can improve function governed by the frontal lobe and neural networks involved in cognition and behavior by stimulating certain areas of the brain with a pacemaker. Douglas W. Scharre, MD, a neurologist and director of the division of cognitive neurology, and Ali R. Rezai, MD, a neurosurgeon and director of the neuroscience program, both at Wexner Medical Center, are conducting the study. “If the early findings that we’re seeing continue to be robust and progressive, then I think that will be very promising and encouraging for us,” says Rezai, who also directs the Center for Neuromodulation at Ohio State. “But so far we are cautiously optimistic.” The DBS implant is similar to a cardiac pacemaker device; however, the pacemaker wires are implanted in the brain rather than the heart. “Basically, the pacemakers send tiny signals into the brain that regulate the abnormal activity of the brain and normalize it more,” Rezai says. The study, which will enroll people with mild or early-stage Alzheimer’s disease, will help determine whether DBS has the potential to improve cognitive, behavioral, and functional deficits. Sanford continues to be evaluated to determine the technology’s effectiveness, according to Rezai. Sanford says she volunteered for the study to help others avoid the angst she has suffered as Alzheimer’s slowly disrupted her life. Alzheimer’s disease, the most common form of degenerative dementia, afflicts about 5.5 million Americans and costs more than $100 billion per year, ranking it the third costliest disease in terms of health care expenditures in the United States. Alzheimer’s disease, which has no cure and is not easily managed, becomes progressively disabling with loss of memory, cognition, and worsening behavioral function, in addition to a gradual loss of independent functioning, says Scharre. The Ohio State neurology team is nationally renowned for expertise in dementia and Alzheimer’s care and research. In addition, the neuromodulation team at Ohio State are pioneers in the use of DBS to treat Parkinson’s disease as well as exploring the use of DBS for other neurological and neurobehavioral conditions. — Source: Ohio State University Wexner Medical Center
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