Small study shows 'no clear clinical benefit' but warrants further research, scientists say.
By Amanda Gardner HealthDay Reporter
WEDNESDAY, Aug. 11 (HealthDay News) -- In an extremely small, early trial, deep brain stimulation appeared to improve memory slightly in several patients with mild Alzheimer's disease.
The authors caution that the findings are very preliminary and that "no clear clinical benefit can be claimed" from the study. However, test results and brain imaging suggest that the procedure may one day hold some promise for the incurable illness, experts said.
"We don't want to overinterpret the results and I agree with the cautions on the one hand, but on the other hand the fact that the PET-scanning data looks so good seems pretty exciting to me," said Dr. Richard Lipton, an attending neurologist at Montefiore Medical Center in New York City and principal investigator of the Einstein Aging Study who was not involved in the deep brain stimulation research.
"Alzheimer's is not a disorder where you break even. It's a disorder where you decline . . . This is not the natural history of Alzheimer's. A successful treatment will leave you one year later where you were when you started," he added.
Deep brain stimulation is already used for people with other neurodegenerative diseases, most notably Parkinson's.
The way the Alzheimer's research came into being was a study in serendipity. In 2003, the same research group was working in a different area: using deep brain stimulation in an attempt to control appetite in an obese patient. The results had an unexpected benefit.
"We tested implanting an electrode in the areas of the brain that controlled appetite while [he was] awake," said Dr. Andres M. Lozano, senior author of a paper appearing in the Annals of Neurology. "While we were inserting the electrodes and turning them on, to our surprise, we were able to unlock some memories of events that happened over 30 years ago in this particular man."
Over time, the researchers also found "important improvements on the performance on memory tests" in this one test patient, said Lozano, who is chairman of neurosurgery at the University of Toronto and Canada Research Chair in Neuroscience.
Based on that discovery, Lozano decided to embark on a study involving Alzheimer's patients. The current phase 1 safety study was a small one, involving only six patients who for 12 months had electrodes planted in and continuously stimulating areas of the brain known to affect memory. All patients stayed on Alzheimer's medications throughout the trial.
"We used two Alzheimer's [measurement] scales commonly used. We expect patients to worsen on these scales over a year," Lozano said. "But we found that some patients did not worsen; some actually improved in their cognitive function."
And in the areas of the brain which are damaged by Alzheimer's, imaging scans turned up heightened glucose metabolism, indicating a higher level of brain activity, Lozano said.
"They're still open for business. They can still be used and activated," he said.
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.
In the small trial, the procedure appeared to be safe, with none of the patients showing weight changes, sleep disturbances or body chemistry abnormalities after the initial surgery, according to the researchers.
However, Lipton noted that deep brain stimulation is an invasive technique. "This is not a procedure free of risk," he said. "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."
Lipton added that the device would have to be approved before it is available for widespread use.
The researchers are now embarking on a larger, phase 2 study.
Lozano also reported a potential conflict of interest, which is that he holds intellectual property in the field of deep brain stimulation (DBS).
(SOURCES: Andres M. Lozano, M.D., Ph.D., chairman, division of neurosurgery, University of Toronto and Canada Research Chair in Neuroscience, Canada; Richard Lipton, M.D., attending neurologist, Montefiore Medical Center, professor and vice chair, neurology, Albert Einstein College of Medicine, and principal investigator, Einstein Aging Study; July 30, 2010, Annals of Neurology online)