As we age, there is a natural decline in cognitive function, even in healthy adults without dementia. A new study shows that a cognitive training program can stimulate the production of a chemical in the brain that plays a role in memory and attention.
Participants who performed game actions through Brain headquarters, The online subscription program showed an increase in the production of acetylcholine, which is sometimes called the “pay attention” chemical. The process that produces acetylcholine in the brain is called the cholinergic system.
Researchers from McGill University in Montreal conducted a clinical study involving 92 people aged 65 years and older. All of them were healthy, that is, they were not diagnosed with a cognitive disorder.
In a study called IMPROVEMENT (Improving Neurological Health in Aging with Computerized Exercises Based on Neuroplasticity) participants were randomly assigned to two groups of 46 people. Both groups were asked to spend 30 minutes a day performing a given activity on a computer or mobile device for 10 weeks.
People in the experimental group completed BrainHQ exercises, while people in the control group played games designed for entertainment.
The researchers used PET, or positron emission tomography, scans and radiotracer to measure acetylcholine production in the participants' brains at the beginning and end of the study.
Participants in the BrainHQ group had a 2.3% increase in acetylcholine production in the anterior cingulate cortex, a part of the brain important for learning, memory, attention, and executive function. There were no significant changes in participants in the control group.
The study claims to be the first of its kind to show that brain training exercises can compensate for natural declines in cholinergic function.
Senior author Dr Etienne de Villers-Sidani, neurologist Neuro (Hospital of the Montreal Neurological Institute)associated with McGill, said his patients often ask how they can keep their minds sharp.
“I’ve always believed that there are things that can have a positive impact on brain health,” said de Villers-Sidani, who is also an assistant professor of neurology and neurosurgery at McGill. “Now I am even more confident that we see that [brain training] has profound effects on the health of key brain chemical systems.”
BrainHQ training was the subject more than 300 studies. A study published last year in the journal Healthcare linked certain BrainHQ exercises to increased visual processing speed in older adults.
But de Villers-Sidani wondered what biochemical changes might be associated with brain training.
“We really wanted to see how these [exercises] change the brain in a more fundamental way,” he said, “by specifically targeting a chemical system that is critical for attention, memory and learning, and also mediates plasticity.”
San Francisco-based Posit Science, the company behind BrainHQ, sponsored the INHANCE study, which was funded by National Institute on Agingpart of the National Institutes of Health. The study results were published Tuesday in the journal. JMIR Serious Games.
How acetylcholine helps you learn, remember
When you learn something new, your brain uses acetylcholine. It tells your brain to stay alert. It is key to other body functions, including blood pressure regulation and contraction of skeletal muscles.
Acetylcholine is a neurotransmitter, meaning it sends messages between neurons and other cells. It is also a neuromodulator that can influence neuron activity.
“It's a chemical that helps us learn, think and remember. It also helps increase alertness,” said Dr. Jennifer Poldurai, a neurologist at Inova Health System in northern Virginia who was not involved in the study. “That's not the only thing going wrong in dementiabut it’s something that’s missing in many types of dementia, including Alzheimer’s.”
Previous studies showed that from 20 to 80 years of age, acetylcholine production declines by approximately 2.5% per decade in the anterior cingulate cortex.
The results from the INHANCE trial are promising, Poldurai said.
“One of the first things I always say is, 'Keep your brain active,'” she said. “We all say this, but no one has actually been able to prove or show objective changes in the brain.”
Playing is not equal to brain training
Research on the relationship between games and puzzles and brain aging has been mixed.
The BrainHQ exercises used in the study are similar to games, but they are not games, says Joaquin Angera, an assistant professor at the Weill Institute for Neuroscience at the University of California, San Francisco. He is also the clinical director of UCSF. Neuroscape center for translational science and has developed brain exercises for use in other cognitive studies.
“Games like Sudoku and crosswords are designed to entertain you; they are designed to engage you and excite you,” said Angera, who was not involved in the trial. “Is there any benefit to them playing? It depends on learning what you're looking for and where you want to see improvement.”
According to de Villers-Sidani, BrainHQ exercises are adaptive, meaning the levels get harder the better you do, and easier the worse you do. People conducting such training must “always be at their best,” he said, noting that the trial exercises simulated real-life stressors, including time limits and distractions.
The two BrainHQ exercises studied in the trial were Double solutionin which people simultaneously identified objects in the center of the screen with both their peripheral vision and Freeze framewhich involves a delay in distinguishing a target image from other similar images.
People in the control group played Double Solitaire and Bricks Breaking Hex, in which players match hexagonal pieces of the same color.

Exercise your body regularly can help you maintain physical health, and regular cognitive muscle training can improve brain health, Poldurai said. But just like going to the gym is different from physical therapy, playing on your phone is not the same as exercising your brain.
“We often have a lot of fun pushing different colored buttons and get rewarded for beating one level or something like that,” she said. “It doesn’t actually force our brains to learn new things, learn complex information, and apply knowledge.”
Can brain training help people with dementia?
The INHANCE study had a number of notable limitations.
Almost 96% of participants were white, most were well educated and lived in the Montreal area. According to de Villers-Sidani, the different visuals used in brain exercises may resonate differently with people of different cultural backgrounds.
Laura Glass Umphleet, an assistant professor of neurology at the Medical College of Wisconsin in Milwaukee, had other concerns. Although McGill scientists collected and analyzed the data, several Posit Science researchers participated in the study, hinting at a bias in favor of BrainHQ in a market saturated with brain training companies.
BrainHQ offers free exercises, but also offers paid subscriptions that cost up to $96 per year, which may be unaffordable for some people. The software also requires an Internet-connected device and some level of technical training, said Umfleet, who was not involved in the testing.
“The cognitive training required daily sessions for 10 weeks,” Umfleet said in an email. “It is impossible to know whether less intense training can be as effective or whether more intense training has diminishing returns.”
De Villers-Sidani said a follow-up study funded by the NIH will determine how people with mild cognitive impairment respond to brain training exercises.
“You have to look at your brain as a physical, medical organ,” Poldurai said. “We still need physical interaction.” She recommends I eat wellgetting 30 minutes of physical activity a day and sleeping seven to eight hours a day.
“Take care of your medical health, take care of your mental health, make friends,” Poldurai said. “And do fun and challenging things with your brain all the time.”