Alzheimer’s: Rewiring the Circuits

Jayne MacAulay | October 23rd, 2013

A novel approach may keep Alzheimer brains humming

On a hot afternoon in August 2003, the lights went out in Ontario and a cluster of states below its border. Suddenly, 50 million people couldn’t escape the fact that modern life relies on electrical circuits.

As brain cells progressively die in people with Alzheimer’s disease (AD), the electrical connection between brain cells similarly shuts down. In time, the outage spreads and the brain actually shrinks. The Alzheimer Society of Canada reports that in 2011, two-thirds of the 747,000 Canadians living with dementia have Alzheimer’s disease.

Independence becomes impossible as cognitive ability fades, so family and friends become caregivers. A few drugs affect symptoms in some patients for a while, but so far there is no cure. Much research has focused on the signature signs of Alzheimer’s – toxic protein beta-amyloid plaques that accumulate in the brain and tau protein tangles that form in neurons. Initially, a vaccine aimed at beta-amyloid caused a dangerous inflammation of brain tissue in some people during a trial, but a new vaccine seems to provoke antibodies safely. Larger trials will have to confirm this.

But sometimes researchers catch a lucky break.

In 2003, Dr. Andres Lozano, a neurosurgeon at Toronto Western Hospital’s Krembil Neuroscience Centre and chairman of neurosurgery at the University of Toronto, discovered a more radical approach that improves activity in brain cell circuits involved in memory. Using a procedure called deep brain stimulation (DBS), he was treating an obese patient who had an out-of-control eating pattern.

As a mild current excited an area of the brain involved in regulation of metabolism, the man suddenly began describing an event that had occurred 30 years earlier. Lozano realized the technique might improve neuron activity in people with Alzheimer’s. Lab studies later showed that stimulating the same area in rats improved spatial memory.

DBS uses a battery-operated device like a cardiac pacemaker, that’s surgically implanted just below the collarbone. A wire is threaded under the skin from the pacemaker and through a small hole in the skull. The brain has no pain receptors, so the patient remains awake under local anesthetic and can respond as electrodes at the wire’s tip stimulate a specific area with a mild current.

“There are some areas of the brain, particularly in the temporal lobe in AD, that are shut down,” Lozano explains. “It’s as if the lights are out. We wanted to know whether those areas of the brain were shut down permanently or whether we could turn them back on. We discovered to our amazement that when we stimulate these circuits in the brain, the brain makes more neurons! It means that maybe we could repair some of the damage that occurs in patients with Alzheimer’s. Our hope is, we may be able to put the brakes on the disease and slow it down,” he says.

Lozano’s team has implanted brain pacemakers in patients with mild Alzheimer’s for a large clinical trial. Initially, only half will receive deep brain stimulation. An earlier trial in Toronto showed that at the two-year mark, memory and problem solving in two patients had declined, but not in two others. One patient had actually improved, much to his – and Lozano’s – delight.

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