The discovery, published Wednesday in the Annals of Neurology, shows how an accidental finding during experimental treatment in a patient with normal memory may open the door to treating the symptoms of Alzheimer’s disease.
Neurosurgeon Dr. Andres Lozano and a team at Toronto Western Hospital had been testing experimental deep brain stimulation to treat a 50-year-old man with a lifelong history of obesity. They had implanted electrode contacts into his hypothalamus, deep in his brain, and were looking for appetite suppressant sites by stimulating the electrodes.
That’s when the patient suddenly experienced a feeling of "déjà vu." He reported the perception of being in a park with friends from when he was around 20 years old. As the intensity of the electrical stimulation was increased, the details became more vivid.
"He understood that it was a sunny day. As we increased the stimulation, more details filled in. The colours of the scene became more vivid," Lozano told.
"This was for us a eureka moment in that we were not expecting it at all."
The contacts that most readily induced the memories were located in the man’s hypothalamus and estimated to be close to the fornix, an arched bundle of fibres that carries signals within the limbic system, which is involved in memory and emotions. Stimulation was shown to drive the activity the temporal lobe and the hippocampus, important components of the brain’s memory circuit.
In the year that followed, the man, who initially had normal memory, began scoring far higher on memory and learning tests — as long as the electrodes, which remained in his brain, were stimulated through electrical currents from a pacemaker implanted near his collarbone.
Deep brain stimulation is currently being used by a handful of doctors to control the tremors of Parkinson’s disease. It’s also being experimented as a tool to lift chronic depression. Now, doctors think they’ve stumbled on to a new way of treating the symptoms of those with memory problems.
"We think that for those patients with Alzheimer’s who are early on in their illness, where their memory is affected, it may be possible to go into circuits and increase their activity and in doing so, enhance their memory function," speculates Lozano.
"This is symptomatic therapy; that is to say, it is a therapy that improves the symptom of the illness. We don’t think it will stop the natural history of the illness. We don’t think it will stop the death of cells that occur in the brain," he adds. "It is something to improve the symptoms of the disease but not something that we expect will stop the disease in its tracks."
Toronto researchers have now implanted the device into six patients with Alzheimer’s to see whether stimulating their memory is safe and if it releases memories locked away by the disease.
"So far, those patients are doing well and there have been no significant side effects of the surgery," says Lozano. "And we have some indications of some aspects of memory may be improving."
For neurologist Sandra Black of Sunnybrook Health Sciences Centre in Toronto, the findings are intriguing, although preliminary.
"I thought that scientifically, it is a very exciting study," she says. But she notes that it may not be a treatment that could be made widely available.
"It involves a very skilled neurosurgery team that would not be widely accessible. It involves putting foreign objects into the brain, and there may be safer alternatives," she says.
There are several dozen experimental drugs being tested for the treatment of Alzheimer’s. But so far, scientists say no medication has come close to restoring memory as profoundly as this deep brain stimulation has done.
The accidental discovery has now led to a pilot study that is underway in Toronto in which Lozano and a team are studying the possibility of improving memory in patients with Alzheimer’s by stimulating the memory circuits in the brain.
Mary-Pat McAndrews, a neuropsychologist who was part of the Lozano research team says the aim is not to cure Alzheimer’s, but to provide Alzheimer’s patients with a longer time in which they could function independently.
"Ideally, what we would be looking for is something that would allow us to provide them with some additional memory assistance and therefore have a real and genuine impact on life," she says.