May 23, 2012 — Deep brain stimulation (DBS), a therapy already approved for use in Parkinson’s disease, may also be useful for treating some patients with early signs of Alzheimer’s disease (AD), a pilot study suggests.
After 1 year of continuous DBS, a clinically meaningful increase in cerebral metabolism in the hippocampal area was observed in 1 of the 5 patients, lead author Gwenn Smith, PhD, from Johns Hopkins University School of Medicine, Baltimore, MD, told Medscape Medical News.
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“The idea to try deep brain stimulation came from a single individual who had morbid obesity and who underwent DBS to try and curb his eating behavior,” Dr. Smith said. “Even though that individual did not have a memory problem at baseline, when the electrodes were turned on, he showed a substantial improvement in memory.”
Because of this result, senior author Andres M. Lozano, MD, PhD, R.R. Tasker Chair in Functional Neurology at the University of Toronto, Canada, decided to try DBS in patients with AD, Dr. Smith said.
DBS is an invasive procedure that involves placing electrodes anterior to the fornix, the pathway that is the major input and output pathway to the hippocampus, the region of the brain most involved in AD. The electrodes provide continuous stimulation to this area of the brain and increase neuronal activity, Dr. Smith explained.
In the open-label trial, the 5 patients with mild probable AD (1 woman and 4 men; mean age, 62.6 years) received DBS. All patients underwent clinical follow-up and high-resolution positron emission tomography of cerebral glucose metabolism at 1 month and then at 1 year.
The study found that overall, the group of 5 patients showed a worsening in their Alzheimer’s Disease Assessment Score-cognition (ADAS-cog) of about 2 points every 6 months. However, 1 patient, who had the best ADAS-cog score at baseline and appeared the least affected, showed improvement, as indicated by a 4-point lower ADAS-cog score after 1 year of DBS.
Also, functional connectivity analyses showed that 1 year of DBS increased cerebral glucose metabolism in the frontal-temporal-parietal-striatal-thalamic network and a frontal-temporal-parietal-occipital-hippocampal network by 15% to 20%.
Patients who had higher baseline metabolism before DBS and increased metabolism after 1 year of DBS had better outcomes in cognition, memory and quality of life.
“Our study was designed to establish safety and only involved a small number of people,” Dr. Smith said. “The next stage, given that these results were encouraging, is to look at a larger sample of individuals and there was some discussion of a larger trial.”
Medscape Medical News invited Michele Tagliati, MD, director of the Movement Disorders Program at Cedars-Sinai Medical Center in Los Angeles, California, and one of the world’s pioneers in DBS, to give his opinion of this study.”This is an exciting study and very elegantly done,” Dr. Tagliati, who uses DBS to treat patients with Parkinson’s disease, said. “Dr. Lozano is one of the champions of the idea that you can treat virtually any brain condition as long as you find the appropriate brain circuitry to modulate.”
The limitation, however, is the small number of patients, and the fact that only 1 patient seemed to improve while the others got worse.
“One of the messages is that we might be able to select patients who have a greater chance of success with DBS,” Dr. Tagliati suggested. “For example, the one patient in this study who showed improvement with DBS was the patient who was least affected by Alzheimer’s disease at baseline. Even early Parkinson’s patients seem to do better than those who are more advanced. This needs to be studied further.”
The study was supported by grants from the Neurosurgical Research and Education Foundation, the Dana Foundation and the Krembil Neuroscience Discovery Fund. Dr. Smith and Dr. Tagliati have disclosed no relevant financial relationships.
Arch Neurol. Published online May 7, 2012.