A New Approach to Treating Alzheimer's

Stimulating memories: Scientists are testing electrical stimulation of the hypothalamus, shown here in green, as a novel treatment for Alzheimer’s disease. The hypothalamus lies adjacent to the fornix, a crucial part of the brain’s memory circuit. Credit: Scott Camazine & Sue Trainor / Photo Researchers, Inc

Earlier this year, neurosurgeon Andres Lozano published a startling finding. He was testing deep-brain stimulation, in which electrical current is delivered directly to the brain, as a treatment for obesity. The patient's weight showed little change, but his memory improved significantly. Lozano has now formed a company to commercialize the technique as an Alzheimer's therapy, and he's testing it in six patients in the early stages of the disease.

Alzheimer's is sorely in need of new treatment approaches. Five million people suffer from it in the United States, a number expected to rise dramatically as the baby boomers enter their senior years. Finding new treatments has proved extremely difficult: drugs currently on the market have at best only a modest impact on symptoms. And experimental drugs that improve cognitive function in animals have largely failed in human tests.

In the past few years, deep-brain stimulation has become a routine treatment for Parkinson's disease: approximately 40,000 patients worldwide have undergone the procedure. Scientists are now testing it as a way to treat a growing number of other disorders, including epilepsy, depression, and obsessive-compulsive disorder.

In the procedure, a thin electrode is surgically implanted into part of the brain, stimulating neurons in brain areas affected by disease. The voltage delivered to the brain is controlled by a power pack implanted in the patient's chest and connected to the electrode via wires threaded beneath the skin.

The patient whose obesity Lozano was attempting to treat is cognitively normal. Lozano's team found that turning on the electrical stimulation triggered old memories in the patient; the higher the voltage, the more details he recalled. More important, after several months of low-level stimulation, cognitive testing revealed that the man's memory significantly improved. "Verbal working memory went off the scale," says Lozano, who holds a Canada Research Chair in Neuroscience at the University of Toronto, in Canada. "We've shown that the function of memory circuits can be modulated."

With Alzheimer's, a neurodegenerative disease that affects brain cells involved in memory, the idea is to boost activity in the memory circuits that patients have left. Lozano's group is targeting the fornix, which he describes as a highway that drives information to and from the brain's memory center, the hippocampus. (The electrode is actually implanted into the neighboring hypothalamus, which was selected for the obesity patient because of its role in controlling appetite. But brain-imaging studies confirm that stimulation triggers activity in the neural circuit that encompasses the fornix and the hippocampus.)

Lozano and his collaborators have seen promising results in the six patients in their trial: turning on the stimulation boosts cognitive function. Lozano now aims to begin larger clinical trials. It's not yet clear how the therapy will fare in the long run. While deep-brain stimulation's success in treating Parkinson's, which is also a neurodegenerative disease, provides some encouragement, other human studies of Alzheimer's therapies that yielded promising early results failed to show effectiveness in later tests.

The researchers are performing parallel experiments in rats and have found that electrical stimulation can drive production of new memories and boost production of new brain cells, which may also boost memory function.

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