Effects of Computerized Cognitive Training on Vesicular Acetylcholine Transporter Levels using [18F]Fluoroethoxybenzovesamicol Positron Emission Tomography in Healthy Older Adults: Results from the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) Randomized Clinical Trial

You do expect your competent? doctor to deliver EXACT PROTOCOLS ON THIS! At least get testing going on unhealthy adults like stroke survivors.

Your competent? doctor needs to recover your 5 lost years of brain cognition due to your stroke.

Do you prefer your doctor, hospital and board of director's incompetence NOT KNOWING? OR NOT DOING?

Effects of Computerized Cognitive Training on Vesicular Acetylcholine Transporter Levels using [18F]Fluoroethoxybenzovesamicol Positron Emission Tomography in Healthy Older Adults: Results from the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) Randomized Clinical Trial

Effects of Computerized Cognitive Training on Vesicular Acetylcholine Transporter Levels using [18F]Fluoroethoxybenzovesamicol Positron Emission Tomography in Healthy Older Adults: Results from the Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) Randomized Clinical Trial

Authors of this article:

Mouna Attarha¹  ;  Ana de Figueiredo Pelegrino²  ;  Lydia Ouellet²  ;  Paule-Joanne Toussaint²  ;  Sarah-Jane Grant¹  ;  Thomas Van Vleet¹  ;  Etienne de Villers-Sidani² 

 

Abstract

Background:The cholinergic system mediates essential aspects of cognitive function, yet its structure and function decline progressively with age, by an estimated 2.5% per decade across the lifespan. Cognitive training may help counteract age-related declines in cholinergic functioning and slow associated deficits in cognitive performance.

Objective:

 This study aims to evaluate whether cognitive training modifies cholinergic binding in older adults.

Methods:The Improving Neurological Health in Aging via Neuroplasticity-based Computerized Exercise (INHANCE) trial is a double-blind randomized controlled trial assessing whether 2 computerized cognitive training programs modify cholinergic expression. The intent-to-treat (ITT) population included 92 community-dwelling healthy older adults aged 65 and above (enrolled July 2021-December 2023; final follow-up June 2024). Participants were randomized at McGill University to either an intervention of speed-based cognitive training exercises designed to improve the speed and accuracy of information processing or an active control of nonspeeded games designed for entertainment (eg, similar in design to Solitaire). Participants completed 35 hours of training on their assigned program at home over a 10-week period using a loaned or personal internet-connected device. Cholinergic binding was measured with the vesicular acetylcholine transporter ligand [¹⁸F]fluoroethoxybenzovesamicol (FEOBV) and positron emission tomography (PET). The primary outcome was mean FEOBV binding (standard uptake value ratios [SUVRs]) within the anterior cingulate cortex from baseline to posttest in the ITT population. All other end points were exploratory.

Results:

Among the 92 participants in the ITT population (mean age 71.9 years; mean education 16.5 years; 61/92, 66%, women; 88/92, 96%, White), 82 (89%) completed all study activities. The speed-based intervention showed a significant within-group increase in FEOBV binding in the primary region of interest, the anterior cingulate cortex (SUVR change mean +0.044, 95% CI 0.006-0.082, P=.03, medium effect size, ω²=0.09). The p24c subregion demonstrated a significant between-groups effect favoring speed training (speeded vs nonspeeded SUVR change difference +0.058, 95% CI 0.007-0.110, P=.03, small effect size, ω²=0.05). Prespecified exploratory analyses revealed significant within-group effects for speed training in the hippocampus (P=.02) and parahippocampal gyrus (P=.04). No effects on FEOBV binding were observed in the active control group.

Conclusions:

INHANCE is the largest FEOBV-PET trial to date and demonstrates, for the first time in humans, that speed training can reverse losses in cholinergic terminal densities in brain regions vulnerable to age-related cognitive decline. The 2.3% gain in FEOBV binding in the anterior cingulate achieved over a 10-week intervention may offset the estimated 2.5% decline typically observed over a decade of natural aging. These findings clarify the neurochemical basis of cognitive training benefits, showing that speed training upregulates binding in networks that support attention, memory, and executive function.

Trial Registration:ClinicalTrials.gov NCT04149457; https://clinicaltrials.gov/study/NCT04149457

International Registered Report Identifier (IRRID):RR2-10.2196/59705

JMIR Serious Games 2025;13:e75161

Mental exercise can reverse a brain change linked to aging, study finds

 You have 5 lost cognitive years from your stroke! Will your competent? doctor create a protocol on this, OR NOT?

Mental exercise can reverse a brain change linked to aging, study finds

Scientists are reporting the first compelling evidence in people that cognitive training can boost levels of a brain chemical that typically declines with age.

A 10-week study of people 65 or older found that doing rigorous mental exercises for 30 minutes a day increased levels of the chemical messenger acetylcholine by 2.3% in a brain area involved in attention and memory.

Your Health

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The increase "is not huge," says Étienne de Villers-Sidani, a neurologist at McGill University in Montreal. "But it's significant, considering that you get a 2.5% decrease per decade normally just with aging."

So, at least in this brain area, cognitive training appeared to turn back the clock by about 10 years.

The chemical change observed after intensive brain training is persuasive, says Michael Hasselmo, director of the Center for Systems Neuroscience at Boston University, who was not involved in the study.

"It was compelling enough that I thought, 'Maybe I need to be doing this,'" he says.

The result backs earlier research in animals showing that environments that stimulate the brain can increase levels of certain neurotransmitters. Studies of people have suggested that cognitive training can improve thinking and memory.

Never skip brain day 

The study, funded by the National Institutes of Health, comes amid a proliferation of online brain-training programs, including Lumosity, Elevate, Peak, CogniFit and BrainHQ.

But it has been hard to know whether these programs really work, says de Villers-Sidani, who directs the cognitive disorders clinic at McGill's Montreal Neurological Institute.

"They had a positive impact on some cognitive measures," he says, "but then the question was, how much is it changing the brain and how is it changing the brain?"

So de Villers-Sidani and a team of researchers decided to see whether mental exercise could increase levels of acetylcholine, a neurotransmitter that's closely associated with cognitive performance.

Acetylcholine levels typically begin a gradual decline around middle age. The levels drop sharply, though, in people with Alzheimer's disease.

The team studied 92 healthy people who were 65 or older.

Shots - Health News

As the U.S. ages, dementia is on the rise. Here are ways to reduce your risk

Half the participants spent 30 minutes a day playing computer games like solitaire and Candy Crush.

The others spent the same amount of time each day doing cognitive exercises that are part of the scientifically tested program BrainHQ. The program challenges users to remember the type and location of items that appear and disappear with increasing speed.

"It's really targeted at attention and speed of processing, and it kind of pushes you to the limit," de Villers-Sidani says.

The researchers used a special kind of PET scan to detect changes in acetylcholine levels in the anterior cingulate cortex, a brain region that's important for making decisions and detecting errors.

"I was not sure we would find anything, to be honest," de Villers-Sidani says.

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But they did. In people who played games like solitaire, acetylcholine levels were unchanged. But in people who did cognitive training, there was a significant increase.

Acetylcholine levels also increased in other brain areas, including the hippocampus, which plays a key role in memory.

Even modest changes are meaningful, Hasselmo says, because acetylcholine does more than carry messages in the brain. It also modulates the behavior of neurons in ways that affect learning, memory and attention.

So when a person takes, say, a high dose of the motion sickness drug scopolamine — which blocks the effects of acetylcholine — things start to go awry.

"If you block the neuromodulator function in the brain, a person can't even think," Hasselmo says. "You go into a delirious state."

On the other hand, even small increases in acetylcholine can have a "profound and notable effect" on memory and thinking in older people.

Hasselmo notes that the earliest Alzheimer's drugs reduced symptoms by increasing levels of acetylcholine. Now, he says, intensive brain training has the potential to achieve similar gains and stave off cognitive decline.

Do Certain Medications Like Benadryl Boost the Risk of Dementia?

 With your already increased risk of dementia, has your doctor warned you of this problem? Known since the late 2000s.

Your risk of dementia, has your doctor told you of this?  Your doctor is responsible for preventing this!

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.`    

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

Do you prefer your doctor incompetence in this NOT KNOWING? OR NOT DOING?

The latest here:

Do Certain Medications Like Benadryl Boost the Risk of Dementia?

A long list of commonly prescribed and over-the-counter drugs may increase your likelihood of developing Alzheimer’s disease and other forms of dementia.

By Gabe AllenJul 19, 2023 9:00 AM

(Credit: The Image Party/Shutterstock)

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Antihistamines like diphenhydramine — the active ingredient in Benadryl, Tylenol PM and many cold medicines — are prescribed and sold over the counter to combat allergic reactions, dry up congestion and aid sleep.

While these drugs are useful, they also leave users feeling confused, sleepy and dizzy. This much is apparent from the inside sticker on a bottle of Benadryl tablets, which warns that “drowsiness may occur” and to “be careful when driving a motor vehicle.”

However, another, longer-term risk is absent from the warning label. A significant body of research has shown that diphenhydramine and other similar drugs increase the risk of developing Alzheimer's disease and other types of dementia.

What Are Anticholinergic Drugs?

Among pharmacologists, the class of medicines that Benadryl belongs to are known as anticholinergic drugs. These compounds suppress the activity of a neurotransmitter called acetylcholine, which is involved in memory and cognition, as well as muscle function elsewhere in the body. Aside from antihistamines, other anticholinergics include antidepressants and medications used to treat an overactive bladder.

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Read More: How Air Pollution Can Increase Risk Factors for Dementia

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In 2015, an investigation in JAMA Internal Medicine analyzed the risk of anticholinergics in 3,434 people over the age of 65 in Seattle over the course of a decade, the largest and longest study to date. The research clearly showed that participants taking anticholinergic drugs developed dementia and Alzheimer’s more often.

Importantly, risk increased along with cumulative dose — meaning that patients that took more doses of an anticholinergic over time were even more likely to develop dementia.

When Did This Association Emerge?

Researchers have long observed that the brains of a patient with Alzheimer’s disease produce less acetylcholine than is normal. In the past, medical scientists have even used a particularly powerful anticholinergic, called scopolamine, to mimic the symptoms of Alzheimer’s in study participants. The same drug is infamous in Colombia, where criminals have used it to render victims docile, confused or unconscious.

For a long time, pharmacologists thought that the delirious side-effects of drugs like scopolamine or benadryl were benign and short-lived. This belief went unchallenged until the early 2000s. Around that time, Indiana University geriatrician, neuroscientist and professor of aging research Malaz Boustani was working with a population of elderly Black patients.

“I noticed, from my own experience with one or two patients in my practice, that stopping these medications didn’t actually improve their brain health,” Boustani says. “So I started to design epidemiological studies to investigate the long-term effect of anticholinergics.”

His research, though confined to small sample sizes at first, clearly showed an association between dementia and anticholinergics. And he wasn’t the only one to notice. Throughout the late 2000s and early 2010s, a flurry of studies linked dementia to anticholinergic use in various geriatric populations.

By the time the JAMA investigation came out, it merely confirmed the obvious: anticholinergics had a dangerous association.

Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme—A plausible missing link for their association with incidence of dementia

You are already under high risk of getting dementia. What the fuck is your doctor EXACTLY doing to prevent that? This prevention is your doctor's responsibility, don't let them weasel out of it. You should get EXACT PROTOCOLS ON PREVENTION. Don't settle for crapola guidelines like the Mediterranean diet, that barely helps because there is no specificity to it.

Your chances of getting dementia.

1. A documented 33% dementia chance post-stroke from an Australian study?   May 2012.

2. Then this study came out and seems to have a range from 17-66%. December 2013.

3. A 20% chance in this research.   July 2013.

4. Dementia Risk Doubled in Patients Following Stroke September 2018 

5. Parkinson’s Disease May Have Link to Stroke March 2017

 

 

Proton pump inhibitors (PPIs) are a class of drugs used to treat GERD, peptic ulcers, and H. pylori.

The currently available PPIs include:

• omeprazole (Prilosec, Prilosec OTC, Zegerid)

• lansoprazole (Prevacid)

• pantoprazole (Protonix)

• rabeprazole (Aciphex)

• esomeprazole (Nexium)

• dexlansoprazole (Dexilant)

  

Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme—A plausible missing link for their association with incidence of dementia

Rajnish Kumar

Amit Kumar

Agneta Nordberg

Bengt Långström

Taher Darreh‐Shori

First published: 08 May 2020

https://doi.org/10.1002/alz.12113

Abstract

Introduction

Several pharmacoepidemiological studies indicate that proton pump inhibitors (PPIs) significantly increase the risk of dementia. Yet, the underlying mechanism is not known. Here, we report the discovery of an unprecedented mode of action of PPIs that explains how PPIs may increase the risk of dementia.

Methods

Advanced in silico docking analyses and detailed enzymological assessments were performed on PPIs against the core‐cholinergic enzyme, choline‐acetyltransferase (ChAT), responsible for biosynthesis of acetylcholine (ACh).

Results

This report shows compelling evidence that PPIs act as inhibitors of ChAT, with high selectivity and unprecedented potencies that lie far below their in vivo plasma and brain concentrations.

Discussion

Given that accumulating evidence points at cholinergic dysfunction as a driving force of major dementia disorders, our findings mechanistically explain how prolonged use of PPIs may increase incidence of dementia. This call for restrictions for prolonged use of PPIs in elderly, and in patients with dementia or amyotrophic lateral sclerosis.

1 INTRODUCTION

The cholinergic system is one of the oldest and the most widely spread neuronal and non‐neuronal signaling systems in the body, and in an evolutionary perspective has acquired regulatory functions in diverse biological processes and organs. The cholinergic neurons and their projections are identified by intracellular presence of the acetylcholine (ACh) bio‐synthesizing enzyme, choline‐acetyltransferase (ChAT). All other downstream neurons and non‐excitable cells which express ACh‐receptors are cholinoceptive cells. The central cholinergic system consists of four “ChAT‐containing” neuronal nuclei (Ch1–Ch4) located in the basal forebrain.1 Ch1 and Ch2 innervate the hippocampal complex, Ch3 the olfactory bulb. Ch4‐neurons are located in the nucleus basalis of Meynert (nbM), which innervate the rest of cerebral cortex and amygdala.1 These cholinergic nuclei and their widespread projections throughout the brain have recently been mapped in detail as a 3D whole‐brain atlas together with the morphology and the connectivity of individual neurons from the basal forebrain.2 In addition, extensive cholinergic neuronal projections, originated from 13 cranial nerves (CN0 and I‐XII, constituting the parasympathetic system3), reach throughout the body, thereby controlling autonomic function of diverse organs, muscles, and glands.4, 5 Another major neuronal system with extensive cholinergic circuitry is the enteric nervous system (ENS), in which about 64% of the neurons are cholinergic.6

A study shows how the brain switches into memory mode

Our doctors with just a little bit of more research help should be able to figure out how to solve memory problems in stroke survivors. But of course, our fucking failures of stroke associations will not followup this research to make it translational. You're continuously screwed. 

A study shows how the brain switches into memory mode

Researchers from Germany and the USA have identified an important mechanism with which memory switches from recall to memorization mode. The study may shed new light on the cellular causes of dementia. The work was directed by the University of Bonn and the German Center for Neurodegenerative Diseases (DZNE). It is being published in the renowned journal “Neuron.”
Because of its shape, the control center of memory bears the poetic name of “hippocampus” (seahorse). New sensations to be stored continually enter this region of the brain. But at the same time, the hippocampus is also the guardian of memories: It retrieves stored information from the depths of memory.
The hippocampus is also an important transport junction. And just like rush hour in a major city, it also needs a regulating hand to control the opposing flows of information. The researchers from Bonn, Los Angeles and Palo Alto have now identified such a memory traffic policeman. Certain cells in the brain, the hippocampal astrocytes, ensure that the new information is given priority. The mind thus switches into memorization mode; by contrast, the already saved memories must wait.
However, the astrocytes themselves only take orders: They react to the neurotransmitter acetylcholine, which is released in particular in novel situations. It has been known for several years that acetylcholine promotes the storage of new information. How this happens has only been partly understood. “In our work, we were able to show for the first time that acetylcholine stimulates astrocytes which then are induced to release the transmitter glutamate,” explains Milan Pabst, who is a doctoral candidate at the Laboratory for Experimental Epileptology of the University of Bonn. “The released glutamate then activates inhibitory nerve cells which inhibit a pathways mediating the retrieval of memories.”
The researchers working with the neuroscientist Prof. Dr. Heinz Beck genetically modified nerve cells so that they could be activated by light and then release acetylcholine. Using this trick, they were able to clarify the mechanism using recordings in living brain tissue sections. “However, we also show that, in the brains of living mice, acetylcholine has the same effect on the activity of the neurons,” explains Pabst’s colleague, Dr. Holger Dannenberg.
Astrocytes have long since been underestimated
Another reason this result is interesting is because astrocytes themselves are not nerve cells. They belong to what are known as glial cells. Until the turn of the millennium, they were still considered to merely serve as mechanical support to the real stars of the brain, the neurons.
In recent decades, however, it has become increasingly clearer that this image is far from correct. It is known by now that astrocytes can release neurotransmitters – the messengers by which neurons communicate with each other – or even remove them from the brain. “It was previously unknown that the astrocytes are involved in central memory processes through the mechanism which has now been discovered,” explains Prof. Beck. However, an observation made by US scientists in 2014 fits into this context: If astrocytes’ function is inhibited, this has a negative effect on the recognition of objects.
The results may also shed new light on the cellular causes of memory disorders. Thus there are indications that the controlled secretion of acetylcholine is disrupted in patients with Alzheimer’s dementia. “However, we have not investigated whether the mechanism we discovered is also impacted,” stresses Pabst.

Microbes Effect on the Brain

This doctors' blog on this is too detailed to summarize so ask your doctor what is being done with this to adjust your stroke protocols for recovery. 

Microbes Effect on the Brain

A couple selected sentences;
Without microbes, there is a much higher level of stress steroids from the hypothalamus (corticosteroids) and a lower level of BDNF, (brain derived neurotrophic factor stimulates new neurons and brain connections).
Mice without microbes have decreases in several important neurotransmitters and factors. BDNF is lower, which affects the development of new brain cells for memory. 
Also, microbes make many other small molecules that can be neuro modulators or new neurotransmitters. This includes serotonin, dopamine, GABA, epinephrine, acetylcholine and others.

Mice without microbes have decreases in several important neurotransmitters and factors. BDNF is lower, which affects the development of new brain cells for memory. - See more at: http://jonlieffmd.com/blog/microbes-effect-on-the-brain#sthash.O7jw4XzD.dpuf

Without microbes, there is a much higher level of stress steroids from the hypothalamus (corticosteroids) and a lower level of BDNF, (brain derived neurotrophic factor stimulates new neurons and brain connections). - See more at: http://jonlieffmd.com/blog/microbes-effect-on-the-brain#sthash.O7jw4XzD.dpuf

Researchers Find Early Success in New Treatment for Stroke Recovery

Ask your doctor for the protocol and how this might help you. 

Researchers Find Early Success in New Treatment for Stroke Recovery

Researchers at The University of Texas at Dallas have taken a step toward developing a new treatment to aid the recovery of limb function after strokes.
In a study published online in the journal Neurobiology of Disease, researchers report the full recovery of forelimb strength in animals receiving vagus nerve stimulation.
“Stroke is a leading cause of disability worldwide,” said Dr. Navid Khodaparast, a postdoctoral researcher in the School of Behavioral and Brain Sciences and lead author of the study. “Every 40 seconds, someone in the U.S. has a stroke. Our results mark a major step in the development of a possible treatment.”
Vagus nerve stimulation (VNS) is an FDA-approved method for treating various illnesses, such as depression and epilepsy. It involves sending a mild electric pulse through the vagus nerve, which relays information about the state of the body to the brain.
Khodaparast and his colleagues used vagus nerve stimulation precisely timed to coincide with rehabilitative movements in rats. Each of the animals had previously experienced a stroke that impaired their ability to pull a handle.

Stimulation of the vagus nerve causes the release of chemicals in the brain known to enhance learning and memory called neurotransmitters, specifically acetylcholine and norepinephrine. Pairing this stimulation with rehabilitative training allowed Khodaparast and colleagues to improve recovery.
Many rehabilitative interventions try to enhance neuroplasticity (the brain’s ability to change) in conjunction with physical rehabilitation to drive the recovery of lost functions, according to Khodaparast. Unfortunately, up to 70 percent of stroke patients still display long-term impairment in arm function after traditional rehabilitation.
“For years, the majority of stroke patients have received treatment with various drugs and/or physical rehabilitation,” Khodaparast said. “Medications can have widespread effects in the brain and the effects can last for long periods of time. In some cases the side effects outweigh the benefits. Through the use of VNS, we are able to use the brain’s natural way of changing its neural circuitry and provide specific and long lasting effects.”

Khodaparast acknowledged the study has some limitations. For example, the animals were young and lacked some of the other illnesses that accompany an aged human population, such as diabetes or hypertension. But Khodaparast and his colleagues said they are optimistic about vagus nerve stimulation as a future tool. They will continue testing in chronically impaired animals with the hopes of translating the technique for stroke patients. Working with MicroTransponder Inc., a partner company in the current study, researchers at the University of Glasgow in Scotland have begun a small-scale trial in humans.
“There is strong evidence that VNS can be used safely in stroke patients because of its extensive use in the treatment of other neurological conditions,” said Dr. Michael Kilgard, professor in neuroscience at UT Dallas and senior author of the study.
Kilgard is also conducting clinical trials using vagus nerve stimulation to treat tinnitus, the medical condition of unexplained ringing in the ears. Kilgard’s lab first demonstrated the ability of vagus nerve stimulation to enhance brain adaptability in a 2011 Nature paper.
Other UT Dallas researchers involved in the study are: postdoctoral fellows Dr. Seth Hays and Dr. Andrew Sloan; graduate student Daniel Hulsey; undergraduate students Andi Ruiz and Maritza Pantoja; and Dr. Robert Rennaker II, associate professor in neuroscience, director of the Texas Biomedical Device Center and head of the Department of Bioengineering.

Yale team finds nicotinic receptor essential for cognition — and mental health

Another reason to have a patch or eCig after your stroke. At least in my opinion and my opinion is worthless, no medical background.
I'm reading this in a paper on schizophrenia, I'm sure your stroke doctor has this on his/her reading list. 

Yale team finds nicotinic receptor essential for cognition — and mental health

One paragraph from there;
Acetycholine is released when we are awake — but not in deep sleep. These receptors allow prefrontal circuits to come “online” when we awaken, allowing us to perform complex mental tasks. This process is enhanced by caffeine in coffee, which increases acetylcholine release. As their name suggests, nicotinic alpha-7 receptors are also activated by nicotine, which may may help to explain why smoking can focus attention and calm behavior, functions of the prefrontal cortex.
Look at that Amy - Coffee