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What does the future hold for the war on Alzheimer’s?

The Question

I've heard that the world's biggest drug company has stopped searching for a cure for Alzheimer's disease. Are there any non-drug treatments in the works?

The Answer

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After spending huge sums on clinical trials in recent years, the pharmaceutical industry has failed to find a drug that can halt the mind-robbing disease. And this month, Pfizer announced it is ending its Alzheimer's research, although other companies haven't thrown in the towel yet. But other prevention measures are being explored.

Several Toronto hospitals are involved in an ambitious $10-million, five-year study to determine whether a combination of cognitive remediation – mental exercises – plus electrical stimulation of the brain can delay the onset of Alzheimer's dementia as well as other forms of dementia.

It's considered to be one of the largest non-drug prevention trials ever attempted for dementia.

The goal is to increase "cognitive reserve" so that patients are able to continue functioning almost normally even as the disease advances, says Dr. Benoit Mulsant, the study's lead principal investigator.

Dr. Mulsant notes that many people develop deposits of amyloid plaque in their brains – a hallmark sign of Alzheimer's disease. The protein deposits eventually interfere with thinking and memory. But some individuals are much slower than others to show outward signs of mental decline. In other words, their brains find ways to work around the detrimental plaque. It's thought that these people have extra mental capacity – or cognitive reserve – to compensate for the mind-altering effects of the amyloid.

Dr. Mulsant and his fellow researchers are trying to boost cognitive reserve with a combination of computer-based brain-training exercises and transcranial direct current stimulation (tDCS), a mild electrical stimulus that puts brain cells into learning mode.

It's hoped this approach will strengthen the prefrontal cortex, a part of the brain that plays a key role in "executive functions," such as problem solving, planning and reasoning.

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"To successfully prevent Alzheimer's dementia, we don't need to block it completely – we just need to delay it by five or 10 years," explains Dr. Mulsant, who is chair of the department of psychiatry at University of Toronto and a clinical scientist at the Centre for Addiction and Mental Health (CAMH).

"So, if you would normally get Alzheimer's at age 78, and we put it off to 88, then you're likely to die of another cause, such as cancer or heart disease, before you develop dementia symptoms," he says.

Funding for the study – which started in 2015 – is coming equally from Brain Canada, a registered charity, and the Chagnon family, Quebec-based philanthropists.

The researchers plan to recruit a total of 425 volunteers who are randomly assigned to receive either the actual treatment or a sham (placebo) therapy for comparison purposes. (In the control group, the volunteers don't get the full brain stimulation and they do less-challenging mental exercises than the treatment group.)

To qualify, volunteers must be experiencing mild cognitive impairment or have previously suffered from depression, which greatly increases the risks of dementia later in life.

So far, 348 people have enrolled in the study, which requires a major time commitment. Volunteers attend classes for two hours a day, five days a week, for two months. During the classes, they don caps that deliver either the real or sham electric current. At the same time, they do computer-based cognitive-training tasks meant to improve memory, concentration and mental flexibility. A therapist also assists the participants.

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After the classes are completed, the participants are encouraged to continue doing the computer tasks at home on a regular basis. Furthermore, every six months, they come back for a one-week refresher course.

The volunteers also undergo extensive cognitive tests and brain imaging.

Even the volunteers getting the control ("sham") therapy are expected to show some benefit, says Dr. Nathan Herrmann, a co-principal investigator and head of geriatric psychiatry at Sunnybrook Health Sciences Centre. Their involvement in the demanding study should increase their cognitive reserve.

The real question, of course, is whether those receiving the actual treatment do substantially better than the control group.

That answer should be revealed in 2020, when the researchers will analyze the first five years of data.

"What we're doing is unique," Dr. Mulsant says. "If it works, we would be the first to find a way to prevent Alzheimer's." He predicts a modified do-it-yourself program could eventually be made available to anyone who wants it.

Health Advisor is a regular column where contributors share their knowledge in fields ranging from fitness to psychology, pediatrics to aging. Follow us @Globe_Health.

Paul Taylor is a patient navigation advisor at Sunnybrook Health Sciences Centre. He is a former health editor of The Globe and Mail. You can find him on Twitter @epaultaylor and online at Sunnybrook's Your Health Matters

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