A chemical critical to brain health showed surprising results in a new study
A recent breakthrough neuroimaging study offers new hope for more effectively addressing the neurological deterioration underlying age-related cognitive loss, pre-dementia, and dementia, as well as other conditions. Researchers from McGill University showed, for the first time in humans, that the brain’s chemical system, which produces the key modulatory neurotransmitter acetylcholine (ACh), can be upregulated by a specific form of online brain training.
In the early 2000s, the drop in forebrain-wide production of ACh was thought to be a principal cause of a brain’s progression to dementia. In the 1970s, physiological psychologists first demonstrated that ACh played a critical role in cortical plasticity processes underlying learning and memory. Researchers in my laboratory—and soon thereafter, in other laboratories—documented its specific role as a crucial enabler of brain-health-sustaining plasticity.
In parallel, medical scientists documented the devastating consequences of shutting down ACh expression by using chemicals that blocked ACh receptors in neurons, “supporting cells” in the cerebral cortex, in subcortical areas, and in the spinal cord. Human subjects treated with high doses of ACh receptor blockers were shown to be functionally akin to individuals with advanced dementia.
The release of ACh increases electrical excitability for inputs feeding the attentionally engaged brain machinery. Brain plasticity (learning and memory) is critically dependent on ACh release.
The INHANCE study that recently reported this ground-breaking rejuvenation in ACh production was conducted by a team led by Dr. Etienne de Villers-Sidani. Their trial randomized 92 older adults to an intervention group, which used online (BrainHQ) brain training for ten weeks for 30 minutes a day, or to a control group, which spent an equal amount of time playing casual online games. All participants underwent cognitive batteries and PET imaging that quantitatively documented forebrain ACh expression, before and after training.
The intervention group showed a significant (and substantial) upregulation in ACh production compared to the attentionally demanding casual games, which had no effect. The upregulation in ACh expression in the experimental group was approximately equal to the typical age-associated downregulation of ACh recorded across an average decade of an older adult.
This finding confirms and advances what we had earlier shown in animal models in my laboratory at UCSF. It’s no accident that this class of exercises has demonstrated cognitive benefits across scores of studies in older adults (in attention, processing speed, episodic and non-declarative memory, learning rate, etc.).
It’s also important to emphasize that the study showed that the form of “brain exercise” adopted by most older individuals—casual games—has no general, neurologically significant, rejuvenating value.
This landmark study opens several important therapeutic windows. First, it indicates that we can potentially use specific behavioral performance indices to monitor the status of key brain chemical systems, on the path to more completely and more intelligently managing the organic brain health in older populations. Second, it bears important implications for the genesis and treatment of depression across populations.
While more work needs to be done, this breakthrough study strikes me as a turning point in how we approach many cognitive conditions.
