April 29, 2024
Batya Swift Yasgur

The concept that cognitive health can be preserved or improved is often expressed as “use it or lose it.” Numerous modifiable risk factors are associated with “losing” cognitive abilities with age and a cognitively active lifestyle may have a protective effect.

But what is a “cognitively active lifestyle” — do crosswords and Sudoku count?

One popular approach is “brain training.” While not a scientific term with an established definition, it “typically refers to tasks or drills that are designed to strengthen specific aspects of one’s cognitive function,” Yuko Hara, PhD, director of Aging and Alzheimer’s Prevention at the Alzheimer’s Drug Discovery Foundation, told Medscape Medical News.

Manuel Montero-Odasso, MD, PhD, director of the Gait and Brain Lab, Parkwood Institute, London, Ontario, Canada, elaborated. “Cognitive training involves performing a definitive task or set of tasks where you increase attentional demands to improve focus and concentration and memory,” he told Medscape Medical News. “You try to execute the new things that you’ve learned and to remember them.”

In a commentary on Medscape Medical News, neuroscientist Michael Merzenich, PhD, professor emeritus at University of California San Francisco, said that growing a person’s cognitive reserve and actively managing brain health can play an important role in preventing or delaying Alzheimer’s disease. Important components of this include brain training and physical exercise.

Brain Training: Mechanism of Action
Montero-Odasso, who is also team leader at the Canadian Consortium on Neurodegeneration in Aging and team co-leader at the Ontario Neurodegenerative Research Initiative, explained that cognitive training creates new synapses in the brain, thus stimulating neuroplasticity.

“When we try to activate networks mainly in the frontal lobe, the prefrontal cortex, a key mechanism underlying this process is enhancement of the synaptic plasticity at excitatory synapses, which connect neurons into networks; in other words, we generate new synapses, and that’s how we enhance brain health and cognitive abilities.”

The more neural connections, the greater the processing speed of the brain, he continued. “Cognitive training creates an anatomical change in the brain.”

Executive functions, which include attention, inhibition, planning, and multitasking, are regulated predominantly by the prefrontal cortex. Damage in this region of the brain is also implicated in dementia. Alterations in the connectivity of this area are associated with cognitive impairment, independent of other structural pathological aberrations (eg, gray matter atrophy). These patterns may precede structural pathological changes associated with cognitive impairment and dementia.

Neuroplasticity changes have been corroborated through neuroimaging, which has demonstrated that after cognitive training, there is more activation in the prefrontal cortex that correlates with new synapses, Montero-Odasso said.

Henry Mahncke, PhD, CEO of the brain training company Posit Science/BrainHQ, explained that early research was conducted on rodents and monkeys, with Merzenich as one of the leading pioneers in developing the concept of brain plasticity. Merzenich co-founded Posit Science and is currently its chief scientific officer.

Mahncke recounted that as a graduate student, he had worked with Merzenich researching brain plasticity. When Merzenich founded Posit Science, he asked Mahncke to join the company to help develop approaches to enhance brain plasticity — building the brain-training exercises and running the clinical trials.

“It’s now well understood that the brain can rewire itself at any age and in almost any condition,” Mahncke said. “In kids and in younger and older adults, whether with healthy or unhealthy brains, the fundamental way the brain works is by continually rewiring and rebuilding itself, based on what we ask it to do.”

If we understand the principles of brain plasticity, “we can build an adaptive brain and give it exercises to rewire in a healthy direction, improving cognitive abilities like memory, speed, and attention,” Mahncke said.

Unsubstantiated Claims and Controversy
Brain training is not without controversy, Hara pointed out. “Some manufacturers of brain games have been criticized and even fined for making unsubstantiated claims,” she said.

A 2016 review found that brain-training interventions do improve performance on specific trained tasks, but there is less evidence that they improve performance on closely related tasks and little evidence that training improves everyday cognitive performance. A 2018 review reached similar conclusions, calling evidence regarding prevention or delay of cognitive decline or dementia through brain games “insufficient,” although cognitive training could “improve cognition in the domain trained.”

“The general consensus is that for most brain-training programs, people may get better at specific tasks through practice, but these improvements don’t necessarily translate into improvement in other tasks that require other cognitive domains or prevention of dementia or age-related cognitive decline,” Hara said.

Hara noted that most brain-training programs “have not been rigorously tested in clinical trials” — although some, such as those featured in the ACTIVE trial, did show evidence of effectiveness.

Mahncke agreed. “Asking whether brain training works is like asking whether small molecules improve health,” he said noting that some brain-training programs are nonsense and not evidence-based. He believes that his company’s product, BrainHQ, and some others are “backed by robust evidence in their ability to stave off, slow, or even reverse cognitive changes.”

BrainHQ is a web-based brain game suite that can be used independently as an app or in group settings (classes and Webinars) and is covered by some Medicare Advantage insurance plans. It encompasses “dozens of individual brain-training exercises, linked by a common thread. Each one is intensively designed to make the brain faster and more accurate,” said Mahncke.

He explained that human brains “get noisy as people get older, like a radio which is wearing out, so there’s static in the background. This makes the music hard to hear, and in the case of the human brain, it makes it difficult to pay attention.” The exercises are “designed to tamp down the ‘noise,’ speed up the brain, and make information processing more accurate.”

Mahncke called this a “bottom-up” approach, in contrast to many previous cognitive-training approaches that come from the brain injury rehabilitation field. They teach “top-down” skills and strategies designed to compensate for deficits in specific domains, such as reading, concentration, or fine motor skills.

By contrast, the approach of BrainHQ is “to improve the overall processing system of the brain with speed, attention, working memory, and executive function, which will in turn impact all skills and activities.”

Supporting Evidence
Mahncke cited several supporting studies. For example, the IMPACT study randomized 487 adults (aged ≥ 65 years) to receive either a brain plasticity–based computerized cognitive training program (BrainHQ) or a novelty- and intensity-matched general cognitive stimulation treatment program (intervention and control group, respectively) for an 8-week period.

Those who underwent brain training showed significantly greater improvement in the repeatable Battery for the Assessment of Neuropsychological Status (RBANS Auditory Memory/Attention) than those in the control group (3.9 vs 1.8, respectively; P =.02). The intervention group also showed significant improvements on multiple secondary measures of attention and memory. The magnitude of the effect sizes suggests that the results are clinically significant, according to the authors.

The ACTIVE study tested the effects of different cognitive training programs on cognitive function and time to dementia. The researchers randomized 2802 healthy older adults (mean age, 74 years) to a control group with no cognitive training or one of three brain-training groups comprising:

In-person training on verbal memory skills
In-person training on reasoning and problem-solving
Computer-based speed-of-processing training on visual attention
Participants in the training groups completed 10 sessions, each lasting 60-75 minutes, over a 5- to 6-week period. A random subsample of each training group was selected to receive “booster” sessions, with four-session booster training delivered at 11 and 35 months. All study participants completed follow-up tests of cognition and function after 1, 2, 3, 5, and 10 years.
At the end of 10 years, those assigned to the speed-of-processing training, now part of BrainHQ, had a 29% lower risk for dementia than those in the control group who received no training. No reduction was found in the memory or reasoning training groups. Participants who completed the “booster” sessions had an even greater reduction: Each additional booster session was associated with a 10% lower risk for dementia.

Montero-Odasso was involved in the SYNERGIC study that randomized 175 participants with mild cognitive impairment (MCI; average age, 73 years) to one of five study arms:

Multidomain intervention with exercise, cognitive training, and vitamin D
Exercise, cognitive training, and placebo
Exercise, sham cognitive training, and vitamin D
Exercise, sham cognitive training, and placebo
Control group with balance-toning exercise, sham cognitive training, and placebo
“Sham” cognitive training consisted of alternating between two tasks (touristic search and video watching) performed on a tablet, with the same time exposure as the intervention training.

The researchers found that after 6 months of interventions, all active arms with aerobic-resistance exercise showed improvement in the ADAS-Cog-13, an established outcome to evaluate dementia treatments, when compared with the control group — regardless of the addition of cognitive training or vitamin D.

Compared with exercise alone (arms 3 and 4), those who did exercise plus cognitive training (arms 1 and 2) showed greater improvements in their ADAS-Cog-13l score, with a mean difference of −1.45 points (P = .02). The greatest improvement was seen in those who underwent the multidomain intervention in arm 1.

The authors noted that the mean 2.64-point improvement seen in the ADAS-Cog-13 for the multidomain intervention is actually larger than changes seen in previous pharmaceutical trials among individuals with MCI or mild dementia and “approaches” the three points considered clinically meaningful.

“We found that older adults with MCI who received aerobic-resistance exercise with sequential computerized cognitive training significantly improved cognition,” Montero-Odasso said. “The cognitive training we used was called Neuropeak, a multidomain lifestyle training delivered through a web-based platform developed by our co-leader Louis Bherer at Université de Montréal.”

He explained that the purpose “is to challenge your brain to the point where you need to make an effort to remember things, pay attention, and later to execute tasks. The evidence from clinical trials, including ours, shows this type of brain challenge is effective in slowing and even reversing cognitive decline.”

A follow-up study SYNERGIC 2.0 is ongoing.

Puzzles, Board Games, and New Challenges
Formal brain-training programs aren’t the only way to improve brain plasticity, Hara said. Observational studies suggested an association between improved cognitive performance and/or lower dementia risk and engaging in number and word puzzles, such as crosswords, cards, or board games.

Some studies suggested that older adults who use technology might also protect their cognitive reserve. Hara cited a US longitudinal study of more than 1800 older adults suggesting that regular internet users had roughly half the risk for dementia compared to nonregular internet users. Estimates of daily internet use suggested a U-shaped relationship with dementia with 0.1-2.0 hours daily (excluding time spent watching television or movies online) associated with the lowest risk. Similar associations between internet use and a lower risk for cognitive decline have been reported in the United Kingdom and Europe.

“Engaging in mentally stimulating activities can increase ‘cognitive reserve’ — meaning, capacity of the brain to resist the effects of age-related changes or disease-related pathology, such that one can maintain cognitive function for longer,” Hara said. “Cognitively stimulating activities, regardless of the type, may help delay the onset of cognitive decline.”

She listed several examples of activities that are stimulating to the brain, including learning a new game or puzzle, a new language, a new dance, and learning how to play a musical instrument.

Montero-Odasso emphasized that the “newness” is key to increasing and preserving cognitive reserve. “Just surfing the internet, playing word or board games or doing crossword puzzles won’t be enough if you’ve been doing these things all your life,” he said. “It won’t hurt, of course, but it won’t necessarily increase your cognitive abilities.”

“For example, a person who regularly engages in public speaking may not improve cognition by taking a public-speaking course, but someone who has never spoken before an audience might show cognitive improvements as a result of learning a new skill,” he said. “Or someone who knows several languages already might gain from learning a brand-new language.”

He cited research supporting the benefits of dancing, which he called “an ideal activity because it’s physical, so it provides the exercise that’s been associated with improved cognition. But it also requires learning new steps and moves, which builds the synapses in the brain. And the socialization of dance classes adds another component that can improve cognition.”

Mahncke hopes that beyond engaging in day-to-day new activities, seniors will participate in computerized brain training. “There’s no reason that evidence-based training can’t be offered in senior and community centers, as yoga and swimming are,” he said. “It doesn’t have to be simply something people do on their own virtually.”

Zoom classes and Medicare reimbursements are “good steps in the right direction, but it’s time to expand this potentially life-transformative intervention so that it reaches the ever-expanding population of seniors in the United States and beyond.”