SAN FRANCISCO — A broadly syndicated article has put the INHANCE Study at the top of the list of brain health breakthroughs for older adults in 2025. With the limited impact of plaque removal on Alzheimer’s, the INHANCE neuroimaging study offered some new hope, by identifying the first intervention to upregulate the production of a key brain chemical known to decline with aging and to plummet with pre-dementia and dementia. The intervention that produced that result was not a drug, but the broadly available brain training app BrainHQ from Posit Science.
The INHANCE Study found 10 weeks’ use of BrainHQ by older adults (for 30 minutes a day) significantly upregulated the chemical system (the “cholinergic system”) in the brain which produces acetylcholine (the “pay attention” chemical), as compared to the control group, which spent an equal amount of time on attentionally-demanding computer games (similar to solitaire and candy crush). The researchers noted that the gains persisted in the follow-up measurement — 90 days after the BrainHQ training ceased.
According to the Altmetric Attention Score — widely used by publishers, researchers, and institutions to measure the reach and influence of academic research — the INHANCE Study journal article is the highest ranked of any article published in the journal, and is already in the top five percent of all 29.9 million research outputs ever tracked by Altmetric (since it started in 2011).
“The global reaction to this breakthrough study has been astonishing,” said Dr. Henry Mahncke, CEO of Posit Science. “We keep hearing from researchers and have tracked thousands of instances of media coverage across 140 countries.”
Acetylcholine is known to decline with advancing age and to be deficient across many conditions, including pre-dementia and dementia, as well as ADHD, bipolar, schizophrenia, anxiety, stress, fatigue, sleep disorders and other mental health ailments.
The most prescribed class of drugs for Alzheimer’s is cholinesterase inhibitors (such as Aricept®), which artificially flood the brain with acetylcholine (by blocking its natural removal), rather than fixing its production at the moment the chemical is needed.
“I think this breakthrough struck a chord with both researchers and journalists, because it provides a means to improve brain health today, as well as new hope in fighting the most intractable brain disorders – many of which involve diminished acetylcholine production. It’s part of the pivot to recognizing we should manage brain health as a biological system — just like we manage heart health and other systems.”
“The training restored cholinergic health to levels typically seen in someone 10 years younger,” said the study’s senior author Dr. Etienne de Villers-Sidani, a research professor at McGill University and neurologist at The Neuro (Montreal Neurological Institute-Hospital), who led the study. “This is the first time any intervention, drug or non-drug, has been shown to do that in humans.”
“Some 20 years ago, Dr. Mike Merzenich, the driving force behind the development of BrainHQ, laid out a plasticity-based model of how brain health and performance declines,” Dr. Mahncke observed. “He focused on three drivers: declines in speed of processing, accuracy of processing, and production of key brain chemicals. Prior studies have shown BrainHQ exercises improve processing speed and accuracy. This study completes the picture of how to harness plasticity to drive improvement in bio-chemical brain health and performance.”
Dr. Mike Merzenich is Professor Emeritus at the University of California, San Francisco, and is widely acknowledged for his discovery that the brain is “plastic” — capable of chemical, structural and functional change — throughout life. Prior to his work, scientists believed the brain was only plastic during childhood. While initially met with skepticism, his work has revolutionized the brain sciences. He’s been honored by each of the US National Academies, awarded a Kavli Laureate in neuroscience, and received many other accolades.
“This study also demonstrates a new non-pharmacological path for addressing many other conditions, beyond aging and dementias,” Dr. Mahncke observed. “It’s another indication that brain exercise, like physical exercise, can play an important role in overall health and lowering risk for chronic diseases.”
“More simply put, this could lower health care costs over time by trillions of dollars,” Dr. Mahncke added.