July 24, 2016
Sharon Begley

For the first time ever, researchers have managed to reduce people’s risk for dementia — not through a medicine, special diet, or exercise, but by having healthy older adults play a computer-based brain-training game.

The training nearly halved the incidence of Alzheimer’s disease and other devastating forms of cognitive and memory loss in older adults a decade after they completed it, scientists reported on Sunday. If the surprising finding holds up, the intervention would be the first of any kind — including drugs, diet, and exercise — to do that.

“I think these results are highly, highly promising,” said George Rebok of the Johns Hopkins Bloomberg School of Public Health, an expert on cognitive aging who was not involved in the study. “It’s exciting that this intervention pays dividends so far down the line.”

The results, presented at the Alzheimer’s Association International Conference in Toronto, come from the government-funded ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) study. Starting in 1998, ACTIVE’s 2,832 healthy older adults (average age at the start: 74) received one of three forms of cognitive training, or none, and were evaluated periodically in the years after.

In actual numbers, 14 percent of ACTIVE participants who received no training had dementia 10 years later, said psychologist Jerri Edwards of the University of South Florida, who led the study. Among those who completed up to 10 60-to-75-minute sessions of computer-based training in speed-of-processing — basically, how quickly and accurately they can pay attention to, process, and remember brief images on a computer screen — 12.1 percent developed dementia. Of those who completed all 10 initial training sessions plus four booster sessions a few years later, 8.2 percent developed dementia.

Such a “dose-response effect” — more intervention, more chance of avoiding dementia — is often a clue that the intervention is, indeed, making a difference.

Nevertheless, the finding of a significant benefit from such a modest intervention long ago had dementia experts scratching their heads.

“It’s hard to understand how such a brief intervention could have a long-lasting impact,” said Dr. Howard Fillit, executive director of the Alzheimer’s Drug Discovery Foundation, which supports pharmaceutical research on the disease. “But you have to respect the data.”

Because the results have not been submitted to a peer-reviewed journal, however, they are considered tentative.

ACTIVE is a well-respected study that, until now, had found only modest effects from cognitive training which, in addition to speed-of-processing, included classroom training in memory or reasoning strategies. Each participant was randomly assigned to receive one of the three or none. The randomization reduced the chances that the different outcomes were the result of, say, more cognitively-spry people choosing to undergo computerized brain training.

There is growing evidence that remaining intellectually engaged (“lifelong learning”) and certain forms of cognitive training can reduce the risk of plain old cognitive decline. But the new ACTIVE findings “are evidence that [that] may hold true for dementia, as well,” said Maria Carrillo, chief science officer of the Alzheimer’s Association.

“Brain training” has been likened to snake oil. Federal regulators accused the makers of Lumosity, for instance, of fraud for suggesting its games could prevent memory loss and dementia; the company paid $2 million this year to settle the charges.

The ACTIVE trial had been somewhat disappointing until now. Participants who trained on one skill did better on that skill right after, as well as five years later, compared to those who had different training or none at all. But training in one skill did not improve the others, suggesting that overall brain function wasn’t getting better. And five years after training, there was no effect on their risk of dementia.

Even then, however, there were hints that speed-of-processing might be different, Rebok said, targeting underlying brain activity and physiology rather than skills, as a 2006 study suggested. In 2013, researchers found that speed-of-processing training might improve such “executive functions” as planning and reasoning. A study published last month reported that it improved brain connectivity and cognitive ability in a way that might slow the descent into dementia.

Improving processing speed “changes fundamental processes in the brain,” said Henry Mahncke, CEO of Posit Science Corporation. “It’s not that one particular link in the brain gets improved, but that the whole brain is rejuvenated,” he said.

The company licensed ACTIVE’s speed-of-processing module as the “Double Decision” exercise in its BrainHQ.com product ($96 a year).

A key question is, if speed-of-processing training can reduce the risk of Alzheimer’s, can more be better? The ACTIVE participants got, at most, 14 hours of it nearly 20 years ago. But “given that 10 to 14 sessions had these benefits, just think what we could do with more,” Edwards said. “We should be thrilled about this.”

Scientists not associated with Posit or the new study said they would be more persuaded if it were clear how speed-of-processing training works its magic.

One possibility is a bootstrapping effect. Maybe people who received speed-of-processing training “did something different over the years,” said Laurie Ryan, who oversees Alzheimer’s research at the National Institute on Aging. “Maybe they changed their lifestyle in some way,” with the training giving them a little cognitive boost that they parlayed into more reading, more travel, more social engagement, and more of other activities that boost “cognitive reserve,” the brain’s cushion against dementia.

In fact, some ACTIVE participantstold scientists that the cognitive boost they felt from the training inspired them to enroll in classes at a local college or keep driving, said Rebok, both of which can keep people socially and intellectually engaged.

Other studies presented at the Alzheimer’s meeting on Sunday provided more evidence for the power of cognitive reserve:

*A traditional “Western” diet of red meat, processed foods, white bread, sugar, and saturated fat has long been associated with cognitive decline, though only in observational studies. But older adults eating that way who had more education, mentally stimulating work, and social engagement did not suffer as much decline, scientists reported. The study followed participants for only three years, however, leaving open the possibility that unhealthy habits eventually catch up with the brain.

*Healthy older adults whose jobs required them to work with people rather than “data or things” also seemed to be protected. They were less likely to develop Alzheimer’s even when they had brain lesions called white matter hyperintensities, which have been linked to the disease.