Use the labels in the right column to find what you want. Or you can go thru them one by one, there are only 34,278 posts. Searching is done in the search box in upper left corner. I blog on anything to do with stroke. DO NOT DO ANYTHING SUGGESTED HERE AS I AM NOT MEDICALLY TRAINED, YOUR DOCTOR IS, LISTEN TO THEM. BUT I BET THEY DON'T KNOW HOW TO GET YOU 100% RECOVERED. I DON'T EITHER BUT HAVE PLENTY OF QUESTIONS FOR YOUR DOCTOR TO ANSWER.
Changing stroke rehab and research worldwide now.Time is Brain!trillions and trillions of neuronsthatDIEeach day because there areNOeffective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.
What this blog is for:
My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.
Showing posts with label memory enhancement. Show all posts
Showing posts with label memory enhancement. Show all posts
Will your competent? doctor ENSURE A PROTOCOL GETS WRITTEN ON THIS? To prevent cognitive decline from your stroke!
Do you
prefer your doctor, hospital and board of director's incompetence NOT
KNOWING? OR NOT DOING? Your choice; let them be incompetent or demand
action!
OH NO! your doctor KNOWS NOTHING AND DOES NOTHING!
From Mediterranean diets to
probiotics, scientists reveal how reshaping the gut microbiome could
help protect brain function, while highlighting why timing may be
critical for slowing cognitive decline.
The gut-brain axis is gaining importance as a modulator of brain functional health. A recent paper in Nutrition Research synthesized evidence from the
literature to show that multiple approaches to manipulating the gut
microbiome share common biological pathways to improve cognitive
performance in adults aged 45 years or older with cognitive impairment or at risk of dementia.
Aging gut microbiota shifts linked to dementia risk
Multiple neurodegenerative disorders like Alzheimer’s disease (AD) are mediatedin part by alterations in the gut-brain axis caused by aging-related shifts in the gut microbiota. Dementia is progressive and irreversible, causing neurological decline and a reduced life expectancy.
This is in contrast to the early stages of cognitive impairment, or
mild cognitive impairment (MCI), when functional deficits can be
detected but typically do not affect daily functioning.
Gut-brain mechanisms underlying cognitive decline
The gut-brain axis is a bidirectional communication system between the central nervous system
and the gut. It involves signaling via nerves, hormones, and
immunological mediators. Recent research has established its important
role in regulating neurodevelopment, mood, and cognition.
However, age- and diet-related changes in the gut microbiota may
induce dysbiosis, which is thought to contribute to the onset of
neurodegeneration.
With gut dysbiosis, the gut epithelial barrier is compromised. This
allows bacteria and microbial-associated molecular patterns to enter the
bloodstream. The resulting systemic endotoxemia may trigger chronic
low-grade inflammation. Gut dysbiosis also causes immune cell
abnormalities, resulting in a systemic pro-inflammatory state.
Systemic inflammation may weaken the blood-brain barrier (BBB),
exposing the brain to pro-inflammatory triggers and mediators. The
resulting neuroinflammation is associated with the accumulation of
abnormal proteins, such as amyloid-β and tau, the hallmark of AD.
Neuronal synapses are damaged, and function is impaired. The eventual
outcome is cognitive decline, whether as a part of aging or of AD.
The microbiome, immune system, and brain are engaged in a continuous
dialogue, where perturbations in one component can reverberate
throughout the system, creating a vicious cycle that promotes cognitive
decline.
Microbiome research evolves from observation to intervention
The researchers outlined the progression of such studies. The
earliest, purely descriptive, studies of gut microbial responses were
followed by detailed microbiome characterizations driven by advances in
DNA and RNA sequencing and metabolomics. This was followed by the
current interventional studies with a stronger mechanistic focus.
Integrating evidence on dysbiosis and cognition
The authors aimed to pull together evidence from studies covering
various microbiota-targeting interventions in isolation. They reviewed
the literature on cognitive changes in adults aged 45 years or older
with cognitive impairment or at risk of dementia who participated in
experimental manipulations of the gut microbiota.
The interventions included probiotics, prebiotics, methyl donor
nutrient supplementation, omega-3 fatty acid intake, synbiotics, fecal
microbiota transplants (FMT), and diets like the Mediterranean or keto
diets. The patients were evaluated for inflammatory and metabolic
changes, as well as alterations in fecal microbiota.
Microbiota changes linked to cognitive improvement
The review included 15 studies covering a range of demographic
characteristics. The study sample ranged from 5 to over 1,200
participants. Overall, there were 4,275 participants.
Summary: A new study finds that urolithin A, a
substance found in pomegranates, can improve memory and may help treat
Alzheimer’s disease. This natural compound works by removing damaged
mitochondria from the brain, similar to the effects of NAD supplements.
While dosage is still being determined, this discovery offers promising
potential for treating and preventing neurodegenerative diseases.
Key Facts:
Urolithin A, found in pomegranates, improves memory and may alleviate Alzheimer’s symptoms
This substance removes damaged mitochondria from the brain, similar to NAD supplements.
Urolithin A is available in pill form, and researchers are working to determine optimal dosage.
Source: University of Copenhagen
A
substance naturally occurring in i.a. pomegranates, strawberries and
walnuts can improve memory and treatment of Alzheimer’s disease, a new
study conducted at the University of Copenhagen concludes.
Forgetfulness,
difficulty finding words and confusion about time and place. These are
some of the most common symptoms of Alzheimer’s disease.
The
researchers still don’t know how much urolithin A is needed to improve
memory and alleviate symptoms of i.a. Alzheimer’s. Credit: Neuroscience
News
Now researchers at the University of Copenhagen have discovered that an ordinary fruit can help.
“Our
study on mouse models with AD shows that urolithin A, which is a
naturally occurring substance in i.a. pomegranates, can alleviate memory
problems and other consequences of dementia,” says Vilhelm Bohr, who is
Affiliate Professor at the Department of Cellular and Molecular
Medicine at the University of Copenhagen and prevoiusly Department Chair
at the US National Institute on Aging.
This is good news for patients with dementia – a disease that is difficult to treat.
“Even
though the study was conducted on mouse models, the prospects are
positive. So far, research has shown promising results for the substance
in the muscles, and clinical trials on humans are being planned.”
Substance improves brain function
The researchers previously discovered that a specific molecule, nicotinamide riboside (NAD supplement), plays
a key role in neurodegenerative diseases such as Alzheimer’s and
Parkinson’s, as it actively helps remove damaged mitochondria from the
brain.
“Many patients with neurodegenerative diseases experience
mitochondrial dysfunction, also known as mitophagy. This means that the
brain has difficulties removing weak mitochondria, which thus accumulate
and affect brain function.
“If you are able to stimulate the
mitophagy process, removing weak mitochondria, you will see some very
positive results,” Vilhelm Bohr explains.
The results of the new
study show that a substance found in pomegranates, urolithin A, removes
weak mitochondria from the brain just as effectively as NAD supplement.
Possible preventive effect
The researchers still don’t know how much urolithin A is needed to improve memory and alleviate symptoms of i.a. Alzheimer’s.
“We
still cannot say anything conclusive about the dosage. But I imagine
that it is more than a pomegranate a day. However, the substance is
already available in pill form, and we are currently trying to find the
right dosage,” Vilhelm Bohr says.
He also hopes the substance can be used for preventive purposes with no significant side effects.
“The
advantage of working with a natural substance is the reduced risk of
side effects. Several studies so far show that there are no serious side
effects of NAD supplementation.
“Our knowledge of urolithin A is
more limited, but as I mentioned, clinical trials with Urolithin A have
been effective in muscular disease, and now we need to look at
Alzheimers disease. ,” he says and adds:
“If we are going to eat
something in the future to reduce the risk of Alzheimer’s, which we talk
a lot about, we have to make sure there are no significant side
effects.”
About this memory and Alzheimer’s disease research news
Author: Sascha Rasmussen Source: University of Copenhagen Contact: Sascha Rasmussen – University of Copenhagen Image: The image is credited to Neuroscience News
Don't do anything with this until maybe 50 years from now it gets into your doctor's medical training. So what if you're dead by then, your current doctor can't be bothered to stay up-to-date on research that might help survivors recover. I can't stand eating wasabi.
But didn't your competent doctor already put these into action for you? Oh, you don't have a competent doctor, do you?
Summary: A recent study investigated the impact of
6-MSITC, a compound found in wasabi, on cognitive functions in older
adults. Over 12 weeks, participants took either a 6-MSITC supplement or a
placebo.
Results showed significant improvements in working and
episodic memory in the 6-MSITC group, though no improvements in other
cognitive areas. This study is the first to demonstrate 6-MSITC’s
potential benefits on memory functions in healthy seniors.
Key Facts:
The
study involved 72 older adults in a double-blinded, randomized
controlled trial, comparing the effects of 6-MSITC supplementation to a
placebo over 12 weeks.
Participants receiving 6-MSITC showed
significant improvements in working memory and episodic memory, while no
significant benefits were observed in other cognitive domains like
processing speed or attention.
This research is pioneering in
demonstrating the positive effects of 6-MSITC, the main bioactive
compound in wasabi, on memory functions in the aging population,
expanding upon previous findings in middle-aged adults.
Source: Neuroscience News
In
a groundbreaking study that could have significant implications for
aging populations worldwide, researchers have uncovered that a compound
found in wasabi, a traditional Japanese spice, may enhance certain
cognitive functions in older adults.
The study, which
focused on the effects of 6-MSITC – the primary bioactive component of
wasabi – on cognitive health, has provided new insights into the
potential benefits of dietary interventions in maintaining and improving
mental functions in the elderly.
However,
the study’s authors caution that more research is needed to fully
understand the effects and potential applications of 6-MSITC in
cognitive health. Credit: Neuroscience News
The Growing Concern of Cognitive Decline in Aging
Cognitive
decline with age is a major concern, as it can significantly impact an
individual’s ability to perform daily tasks and maintain independence.
As the global population ages, there is an increasing focus on finding
ways to preserve cognitive health in older adults. Previous research has
indicated that nutrition plays a crucial role in cognitive health, with
certain diets and food components showing promise in supporting mental
functions.
Wasabi: A Spice with Potential Cognitive Benefits
Wasabi,
known for its unique flavor and heat, has been a staple in Japanese
cuisine for centuries. Beyond its culinary uses, wasabi contains
6-Methylsulfinylhexyl Isothiocyanate (6-MSITC), a compound that has been
shown to have antioxidant and anti-inflammatory properties.
These
properties are believed to be critical in combating cognitive decline,
making 6-MSITC a compound of interest in the quest to support cognitive
health in the elderly.
The Study: Methodology and Participants
The
study’s methodology was robust, involving a double-blinded, randomized
controlled trial (RCT). Seventy-two older adults were randomly assigned
to two groups: one receiving a 6-MSITC supplement and the other a
placebo.
Over a period of 12
weeks, these participants, all aged 60 and above, were given either the
wasabi compound or a placebo. The researchers then evaluated a range of
cognitive abilities, including executive function, memory, processing
speed, and attention, both before and after the intervention.
Significant Findings: Memory Improvement
The
results were notable. Participants who received the 6-MSITC supplement
showed a significant improvement in both working and episodic memory
performances compared to the placebo group.
These findings are
especially important as they demonstrate, for the first time, the
potential of 6-MSITC to enhance memory functions in older adults.
However, it’s important to note that the study did not find significant
improvements in other cognitive areas such as processing speed,
attention, or executive function.
Understanding the Impact on Memory Functions
The
improvement in memory functions, particularly working memory and
episodic memory, is significant. Working memory is crucial for
reasoning, decision-making, and behavior, while episodic memory plays a
key role in personal history and experiences. The improvement in these
areas can greatly affect the quality of life and independence in older
adults.
The Potential Mechanism Behind the Benefits
While
the study did not delve deeply into the biological mechanisms behind
the improvements, the anti-oxidant and anti-inflammatory properties of
6-MSITC are thought to play a critical role. These properties may help
protect against brain damage and enhance neural functions in key areas
of the brain like the hippocampus, which is vital for memory.
Comparisons with Previous Studies
This
study builds upon previous research that has shown beneficial effects
of 6-MSITC on cognitive functions in middle-aged adults. The current
study extends these findings to a healthy older adult population,
providing evidence that the benefits of 6-MSITC are not limited to those
with existing cognitive complaints or younger age groups.
Implications and Future Directions
The
findings of this study have exciting implications. They suggest that
incorporating foods high in beneficial compounds like 6-MSITC could be a
simple, natural way to support cognitive health in older adults.
However,
the study’s authors caution that more research is needed to fully
understand the effects and potential applications of 6-MSITC in
cognitive health.
Limitations and Considerations
The
study is not without its limitations. For instance, the lack of
measurement of biomarkers for antioxidants or anti-inflammatories means
that the exact biological mechanism behind the observed benefits remains
speculative.
Additionally, the study’s focus on healthy older
adults leaves open the question of whether similar benefits would be
observed in younger populations or those already experiencing cognitive
decline.
Conclusion: A Step Forward in Cognitive Health Research
In
conclusion, this study represents a significant step forward in
understanding how dietary components like those found in wasabi can
impact cognitive health in older adults.
While further research is
needed, the potential for natural interventions to support memory and
other cognitive functions is an exciting prospect, offering hope for
improved quality of life and independence for aging populations
worldwide.
Among older adults with relatively poor habitual diets, daily flavanol intake can improve hippocampal-dependent memory.
The dietary consumption of flavanols, which are found
in a number of fruits and vegetables, can improve hippocampal-dependent
memory in older adults with relatively poor habitual diets, according
to study findings published in the Proceedings of the National Academy of Science.
Prior analyses have shown that the consumption of flavanols might
lead to improvement in the hippocampal-dependent memory component of
cognitive aging.
For the study, COcoa Supplement and Multivitamin Outcomes Study-Web (COSMOS-Web; ClinicalTrials.gov Identifier: NCT04582617),
researchers included a total of 3,562 participants (mean age, 71) who
were non-Hispanic/non-Latinx White individuals; most had college or
postcollegiate degrees. The researchers randomly assigned participants
to receive cocoa extract (ie, 500 mg of cocoa flavanols per day;
n=1,744) or placebo (n=1,818).
The primary study outcome was the ModRey, which was used as the
cognitive measure of hippocampal memory. Secondary outcomes included the
Color/Directional Flanker Task, which is a cognitive measure of
prefrontal cortex function, and the ModBent, which was recently designed
as a measure with sensitivity to the function of dentate gyrus.
[F]lavanol
consumption might be considered in future dietary recommendations,
perhaps together with the flavanol biomarker, specifically geared toward
preventing or improving brain health in later life.
The researchers found that participants in both groups showed a typical learning (practice) effect with similar improvements (d= .025; P
=.42). After 1-year, they also found that the flavanol intervention did
not have an effect on ModBent results or performance on the Flanker
test.
The researchers stratified participants into tertiles based on their
diet quality measured by the alternative Healthy Eating Index (aHEI).
For participants who had a poor diet at baseline, those in the lowest
tertile had poorer hippocampal-dependent memory performance, but not
memory related to the prefrontal cortex.
Compared with placebo, the flavanol intervention improved performance
on the ModRey test in participants in the low aHEI tertile (overall
effect: d =.086; P =.011)
Additionally, a urine-based biomarker of flavanol intake —
5-(3′,4′-dihydroxyphenyl)-γ-valerolactone metabolite (gVLM) — was
evaluated in a subset of 1,361 individuals. Via use of these measures,
the researchers revealed that there was a correlation with hippocampal-dependent memory.
When the researchers stratified these results into tertiles, they
found that performance on the ModRey significantly improved with the
dietary flavanol intervention (overall effect: d =.141, P =.006) in the lowest gVLM tertile.
For these participants, when they consumed the dietary flavanol,
their flavanol levels went back to normal and their memory was restored,
the researchers noted.
The researchers did acknowledge that the mechanism behind flavanols and improved memory is not clear.
Study limitations included a lack of generalizability as the results only applied to older adults and a weaker effect size.
“Our findings suggest that flavanol consumption might be considered
in future dietary recommendations, perhaps together with the flavanol
biomarker, specifically geared toward preventing or improving brain
health in later life,” the researchers concluded.
Disclosure: Some of the study authors have declared affiliations
with biotech, pharmaceutical, and/or device companies. Please see the
original reference for a full list of authors’ disclosures.
Does your hospital have enough competence
to have the dietician create protocols on this for the hospital food and
for when you leave? IF NOT, you don't have a functioning stroke hospital.
Summary: A new study establishes the critical role
of flavanols, nutrients found in certain fruits and vegetables, in
mitigating age-related memory loss.
The research shows a
correlation between flavanol intake and scores on memory tests among
older adults. A remarkable improvement was observed in individuals over
60 with low-flavanol diets, after these dietary components were
replenished.
This supports the emerging understanding that specific nutrients are vital for maintaining optimal health in the aging brain.
Key Facts:
The study is the first to conclusively show that a diet low in flavanols contributes to age-related memory loss.
Supplementing flavanols in mildly flavanol-deficient adults over 60 significantly improved their performance in memory tests.
The
research supports the theory that the aging brain, much like a
developing one, requires specific nutrients for optimal health.
Source: Columbia University
A
large-scale study led by researchers at Columbia and Brigham and
Women’s Hospital/Harvard is the first to establish that a diet low in
flavanols—nutrients found in certain fruits and vegetables—drives
age-related memory loss.
The study found that flavanol
intake among older adults tracks with scores on tests designed to detect
memory loss due to normal aging and that replenishing these bioactive
dietary components in mildly flavanol-deficient adults over age 60
improves performance on these tests.
“The improvement among study
participants with low-flavanol diets was substantial and raises the
possibility of using flavanol-rich diets or supplements to improve
cognitive function in older adults,” says Adam Brickman, PhD, professor
of neuropsychology at Columbia University Vagelos College of Physicians
and Surgeons and co-leader of the study.
The
finding also supports the emerging idea that the aging brain requires
specific nutrients for optimal health, just as the developing brain
requires specific nutrients for proper development. Credit: Neuroscience
News
The
finding also supports the emerging idea that the aging brain requires
specific nutrients for optimal health, just as the developing brain
requires specific nutrients for proper development.
“The identification of nutrients critical for the proper development
of an infant’s nervous system was a crowning achievement of 20th century
nutrition science,” says the study’s senior author, Scott Small, MD,
the Boris and Rose Katz Professor of Neurology at Columbia University
Vagelos College of Physicians and Surgeons.
“In this century, as
we are living longer research is starting to reveal that different
nutrients are needed to fortify our aging minds. Our study, which relies
on biomarkers of flavanol consumption, can be used as a template by
other researchers to identify additional, necessary nutrients.”
Age-related memory loss linked to changes in hippocampus
The
current study builds on over 15 years of research in Small’s lab
linking age-related memory loss to changes in the dentate gyrus, a
specific area within the brain’s hippocampus—a region that is vital for
learning new memories—and showing that flavanols improved function in
this brain region.
Additional research, in mice, found that flavanols—particularly a
bioactive substance in flavanols called epicatechin—improved memory by
enhancing the growth of neurons and blood vessels and in the
hippocampus.
Next, Small’s team tested flavanol supplements in
people. One small study confirmed that the dentate gyrus is linked to
cognitive aging. A second, larger trial showed that flavanols improved
memory by acting selectively on this brain region and had the most
impact on those starting out with a poor-quality diet.
In the new
study, the Columbia team collaborated with researchers at Brigham and
Women’s Hospital studying the effects of flavanols and multivitamins in
COSMOS (COcoa Supplements and Multivitamin Outcomes Study).
The
current study, COSMOS-Web, was designed to test the impact of flavanols
in a much larger group and explore whether flavanol deficiency drives
cognitive aging in this area of the brain.
Study methods
More
than 3,500 healthy older adults were randomly assigned to receive a
daily flavanol supplement (in pill form) or placebo pill for three
years. The active supplement contained 500 mg of flavanols, including 80
mg epicatechins, an amount that adults are advised to get from food.
At
the beginning of the study, all participants completed a survey that
assessed the quality of their diet, including foods known to be high in
flavanols.
Participants then performed a series of web-based
activities in their own homes, designed and validated by Brickman, to
assess the types of short-term memory governed by the hippocampus.
The
tests were repeated after years one, two, and three. Most of the
participants identified themselves as non-Hispanic and white.
More than a third of the participants also supplied urine samples
that allowed researchers to measure a biomarker for dietary flavanol
levels, developed by co-study authors at Reading University in the UK,
before and during the study.
The biomarker gave the researchers a
more precise way to determine if flavanol levels corresponded to
performance on the cognitive tests and ensure that participants were
sticking to their assigned regimen (compliance was high throughout the
study).
Flavanol levels varied moderately, though no participants were severely flavanol-deficient.
People with mild flavanol deficiency benefited from flavanol supplement
Memory
scores improved only slightly for the entire group taking the daily
flavanol supplement, most of whom were already eating a healthy diet
with plenty of flavanols.
But at the end of the first year of
taking the flavanol supplement, participants who reported consuming a
poorer diet and had lower baseline levels of flavanols saw their memory
scores increase by an average of 10.5% compared to placebo and 16%
compared to their memory at baseline.
Annual cognitive testing showed the improvement observed at one year was sustained for at least two more years.
The
results strongly suggest that flavanol deficiency is a driver of
age-related memory loss, the researchers say, because flavanol
consumption correlated with memory scores and flavanol supplements
improved memory in flavanol-deficient adults.
The findings of the
new study are consistent with those of a recent study, which found that
flavanol supplements did not improve memory in a group of people with a
range of baseline flavanol levels. The previous study did not look at
the effects of flavanol supplements on people with low and high flavanol
levels separately.
“What both studies show is that flavanols have no effect on people who don’t have a flavanol deficiency,” Small says.
It’s
also possible that the memory tests used in the previous study did not
assess memory processes in the area of the hippocampus affected by
flavanols. In the new study, flavanols only improved memory processes
governed by the hippocampus and did not improve memory mediated by other
areas of the brain.
Next steps
“We cannot yet definitively
conclude that low dietary intake of flavanols alone causes poor memory
performance, because we did not conduct the opposite experiment:
depleting flavanol in people who are not deficient,” Small says, adding
that such an experiment might be considered unethical.
The next
step needed to confirm flavanols’ effect on the brain, Small says, is a
clinical trial to restore flavanol levels in adults with severe flavanol
deficiency.
“Age-related memory decline is thought to occur
sooner or later in nearly everyone, though there is a great amount of
variability,” says Small. “If some of this variance is partly due to
differences in dietary consumption of flavanols, then we would see an
even more dramatic improvement in memory in people who replenish dietary
flavanols when they’re in their 40s and 50s.”
More information
The
study, titled “Dietary flavanols restore hippocampal-dependent memory
in older adults with lower diet quality and habitual flavanol
consumption,” was published in Proceedings of the National Academy of Sciences.
All authors: Adam
M. Brickman (Columbia), Lok-Kin Yeung (Columbia), Daniel M. Alschuler
(New York State Psychiatric Institute), Javier I. Ottaviani (Mars Edge),
Gunter G.C. Kuhnle (University of Reading), Richard P. Sloan
(Columbia), Heike Luttman-Gibson (Brigham and Women’s Hospital/Harvard),
Trisha Copeland (Brigham and Women’s/Harvard), Hagen Schroeter (Mars
Edge), Howard D. Sesso (Brigham and Women’s/Harvard), JoAnn E. Manson
(Brigham and Women’s/Harvard), Melanie Wall (Columbia), and Scott A.
Small (Columbia).
Funding: The study was
supported by grants from Mars Edge, a segment of Mars Inc., and the
National Institutes of Health (AG050657, AG071611, EY025623, and
HL157665).
Is your doctor competent enough to see this and immediately prescribe a protocol on vitamins for you immediately post stroke? You do want your memory boosted and cognitive decline slowed?
Do you prefer your doctor incompetence NOT KNOWING? OR NOT DOING?
Compared with placebo, participants who took a daily
multivitamin/multimineral supplement had significantly better immediate
recall at 1 year (P=0.025) and across 4 years of follow-up on average (P=0.011), reported Adam Brickman, PhD, of Columbia University in New York City, and co-authors in the American Journal of Clinical Nutritionopens in a new tab or window.
Multivitamins improved memory performance above placebo by the
equivalent of 3.1 years of age-related memory change, the researchers
estimated. The effect was more pronounced in people with underlying
cardiovascular disease.
The findings are consistent with data from COSMOS-Mind,opens in a new tab or window
another COSMOS ancillary study that showed daily multivitamin use led
to better cognition, episodic memory, and executive function. Effects in
COSMOS-Mind also were more pronounced in people with cardiovascular
disease history.
"There is evidence that people with cardiovascular disease may have
lower micronutrient levels that multivitamins may correct, but we don't
really know right now why the effect is stronger in this group,"
Brickman said in a statement.
"Supplementation of any kind shouldn't take the place of more
holistic ways of getting the same micronutrients," he cautioned. "Though
multivitamins are generally safe, people should always consult a
physician before taking them."
COSMOS-Web was designed to examine the effects of dietary flavanol or
multivitamin supplementation on hippocampus-mediated cognition in older
adults after 1 year.
"There is converging work that the hippocampus is particularly
susceptible to the effects of normal aging and our previous intervention
studies with dietary supplementation showed a positive effect on the
hippocampus, indexed both by neuroimaging and neuropsychological
assessment," Brickman and colleagues wrote.
The COSMOS-Web cognitive battery included neuropsychological outcome
measures designed to be sensitive to cognitive changes typically seen in
older adults, they added.
COSMOS-Web was embedded in the parent COSMOSopens in a new tab or window
trial, which tested cocoa flavanol extract versus placebo or a Centrum
Silver daily multivitamin versus placebo in people 60 and older.
(Flavanol data will be reported in a separate paper, the authors noted.)
Randomization occurred between April 2016 and March 2018.
The COSMOS-Web primary outcome was performance after 1 year on the Modified Rey Auditory Verbal Learning (ModRey)opens in a new tab or window
immediate recall test of 20 words. Secondary outcomes included change
in ModRey immediate recall performance after 2 and 3 years, ModRey
retention (ratio of delayed recall to immediate recall, which relates to
entorhinal cortex function), and performance on tests of novel object
recognition and executive function. Tests were administered through a
web-based platform.
The intention-to-treat analysis included 3,562 participants
randomized to multivitamin or placebo who completed at least one
follow-up measurement at year 1, 2, or 3. Demographic characteristics
and baseline performance measures were similar between groups.
Pill compliance was 94.4% at 6 months and 91.8% at 1 year. In a small
subset, the researchers assessed blood samples and confirmed increases
in folate, vitamin B12, and serum 25(OH)vitamin D with multivitamin
supplementation versus placebo.
Compared with those on placebo, participants receiving multivitamin
supplementation had significantly greater improvement in ModRey
immediate recall memory between baseline and year 1. In the multivitamin
group, performance improved from a mean of 7.10 words at baseline to
7.81 words at 1 year; in the placebo group, it rose from 7.21 words to
7.65 words.
The average improvement in memory compared with placebo appeared to
be sustained over at least 3 years post-baseline. Secondary outcomes did
not differ significantly between groups in any of the follow-up years.
In participants with a history of cardiovascular disease, the effect
versus placebo on ModRey scores was higher at 1 year (mean difference of
1.24 words, P=0.009) than it was for people without underlying cardiovascular disease.
"The finding that a daily multivitamin improved memory in two
separate cognition studies in the COSMOS randomized trial is remarkable,
suggesting that multivitamin supplementation holds promise as a safe,
accessible, and affordable approach to protecting cognitive health in
older adults," said co-author JoAnn Manson, MD, of Brigham and Women's
Hospital in Boston.
The results might not apply to all older adults, the researchers
acknowledged. The sample consisted mostly of white, educated adults.
People were required to have a computer and internet connectivity to
participate in the study.
Judy George
covers neurology and neuroscience news for MedPage Today, writing about
brain aging, Alzheimer’s, dementia, MS, rare diseases, epilepsy,
autism, headache, stroke, Parkinson’s, ALS, concussion, CTE, sleep,
pain, and more. Follow
Disclosures
The study was
supported by grants from Mars Edge and the National Institutes of
Health. Multivitamins were supplied by Pfizer (now Haleon).
Researchers
reported relationships with Pure Encapsulations, Pfizer, Council for
Responsible Nutrition, BASF, NIH, and the American Society of Nutrition.
Primary Source
American Journal of Clinical Nutrition
Source Reference: opens in a new tab or windowYeung
L-K, at al "Multivitamin supplementation improves memory in older
adults: A randomized clinical trial" Am J Clin Nutr 2023; DOI:
10.1016/j.ajcnut.2023.05.011.
— Novel NMDA-targeted drug would expand options for symptomatic treatment
by
John Gever, Contributing Writer, MedPage Today
April 7, 2022
SEATTLE -- A first-in-class oral compound targeting
N-methyl-D-aspartate (NMDA) receptors proved beneficial in a mid-stage
clinical trial in Alzheimer's disease, setting the groundwork for a full
safety and efficacy study, a researcher said here.
SAGE-718, a positive allosteric modulator (PAM) of NMDA receptor
activity, improved mean scores on five standard memory tests in 26
Alzheimer's patients with mild cognitive deficits, reported Aaron
Koenig, MD, of drugmaker Sage Therapeutics in Cambridge, Massachusetts.
These
included a 2.3-point gain in Montreal Cognitive Assessment (MoCA) score
over the 28-day study, a 50% improvement in digit symbol substitution,
an average 6.9 fewer errors relative to baseline performance on a
multitasking test, and a 1.1-point increase on a 5-point verbal
recognition test scale, Koenig told attendees at a late-breaking
abstract session during the American Academy of Neurology annual meeting.
Moreover, these improvements came without a change in psychomotor
performance, meaning that participants were not simply hitting buttons
faster during the cognitive tests, he noted.
Sage is developing the agent for several types of cognitive deficits,
including those related to Huntington's and Parkinson's diseases, as
well as Alzheimer's. A placebo-controlled phase II study is now underway
in patients with Huntington's disease, and Sage said it plans to open similar trials for other indications this year.
For the current open-label study, Koenig and colleagues enrolled
patients with mild cognitive impairment or mild dementia (Clinical
Dementia Rating [CDR] of 0.5-1.0) believed to stem from Alzheimer's
disease, and MoCA scores of 15 to 24 at baseline. Patients initially
completed the battery of five cognitive tests and the psychomotor
evaluation, then received SAGE-718 (no generic name has been officially
assigned yet) at 3 mg each morning for 2 weeks. The drug was stopped for
2 weeks, and patients repeated the test suite on day 28.
Mean
patient age was 67. About 70% were women, and 80% were white. MoCA
scores at baseline averaged 20.7, and about 90% of the group had a CDR
score of 0.5.
Seven of the 26 participants had adverse events during the study,
with six of the events considered drug-related. Koenig did not give
specifics, but he noted that none were considered serious and no one
discontinued the treatment because of them. Lab values were all normal,
and there were no signs of suicidal ideation or behavioral changes.
"These results support further clinical evaluation of SAGE-718" for
memory deficits related to neurodegenerative diseases, Koenig said.
It's certainly a fertile territory for drug development. Attention
and research money in recent years has been heavily weighted toward
disease-modifying therapies, such as those targeting beta-amyloid for
Alzheimer's disease. Payoffs have been slow in coming, however.
Meanwhile, currently available drugs that aim to boost memory are only
moderately effective and not for very long.
Among
the latter is memantine (Namenda), which is a broad NMDA receptor
antagonist. Because it is not highly effective, memantine is usually
paired with an acetylcholinesterase inhibitor, bringing the risks that
come with polypharmacy. Researchers have more recently come to believe
that PAMs are a better way
to modify receptor activity and may prove more effective. That,
however, will only be known when randomized placebo-controlled studies
are completed.
John Gever was Managing Editor from 2014 to 2021; he is now a regular contributor.
Disclosures
The study was funded by Sage Therapeutics.
Koenig and most other authors were Sage employees.
This will require lots of human testing. Low levels of KYNA lead to Alzheimer’s and Parkinson’s while high levels lead to schizophrenia. I wouldn't want to be in this clinical trial if the range is that delicate.
Diána Martos 1, Bernadett Tuka 1, Masaru Tanaka 1, László Vécsei 1,2,*, and Gyula Telegdy 3
1 MTA-SZTE Neuroscience Research Group, Hungarian Academy of Sciences-University of Szeged (MTASZTE), Semmelweis u. 6, Szeged, H-6725 Hungary
2 Department of Neurology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis u. 6, H6725 Szeged, Hungary
3 Department of Pathophysiology, Albert Szent-Györgyi Medical School, University of Szeged, Semmelweis
u. 5, H-6725 Szeged, Hungary
* Correspondence: vecsei.laszlo@med.u-szeged.hu; Tel.: +36 62 342 361
Abstract:
Kynurenic acid (KYNA) is an endogenous tryptophan (Trp) metabolite known to possess
neuroprotective property. KYNA plays critical roles in nociception, neurodegeneration, and neuroinflammation. A lower level of KYNA is observed in patients with neurodegenerative diseases
such as Alzheimer’s and Parkinson’s diseases or psychiatric disorders such as depression and autism spectrum disorders, whereas a higher level of KYNA is associated with the pathogenesis of
schizophrenia. Little is known about the optimal concentration for neuroprotection and the threshold for neurotoxicity. In this study the effects of KYNA on memory functions were investigated by
passive avoidance test in mice. Six different doses of KYNA were administered intracerebroventricularly to previously trained CFLP mice and they were observed following 24 hours. High doses of
KYNA (i.e., 20-40 μg/2 μl) significantly decreased the avoidance latency, whereas a low dose of
KYNA (0.5 μg/2 μl) significantly elevated it compared with controls, suggesting that the low dose
of KYNA enhanced memory function. Furthermore, six different receptor blockers were applied to
reveal the mechanisms underlying the memory enhancement induced by KYNA. The series of tests
revealed the possible involvement of the serotonergic, dopaminergic, α and β adrenergic, and opiate
systems in the nootropic effect. The study confirmed that a low dose of KYNA improved a memory
component of cognitive domain, which was mediated by, at least in part, four systems of neurotransmission in an animal model of learning and memory.
Keywords: tryptophan; kynurenine; kynurenic acid; passive avoidance; cognitive domain; memory;
cognitive enhancer; neurotransmission; receptor blockers; translational
1. Introduction
Worldwide, around 50 million people suffer from major neurocognitive disorders.
Alzheimer’s disease (AD) represents 60-70 percent of cases, imposing a physical, psychological, social, and economic burden on the elderly, their families, caregivers as well as
society [1]. Patients who develop AD first demonstrate a subtle decline in memory and
learning, followed by changes in executive cognitive function and in language and
visuospatial processing; indeed, recent evidence suggests that impairments in the ability
to process contextual information and in the regulation of responses to threat are related
to structural and physiological alterations in the prefrontal cortex (PFC) and medial temporal lobe, addressing how this progressive brain deterioration can eventually cause patterns of cognitive dysfunctions observed in patients with AD [2]. The cause of major neurocognitive disorders remains unknow, but it is considered to be caused by convergence
of multifactorial factors including genetic, environmental, infectious, and nutritional components, and lifestyle, among others [3,4]. There is no remedy for neurodegenerative diseases. Disease-modifying and symptom-relieving measures are mainstays of treatment.
Thus, a tremendous effort has been made to identify pathomechanisms, discover interventional targets, and design novel pharmaceutical agents [5].
KYNA is a metabolite of the Trp-kynurenine (KYN) metabolic system, known to possess neuroprotective property [6Encyclopedia]. The neuroprotective activities are considered to be attributed to the antagonism of the excitatory amino acid receptors (EAARs)
such as the N-methyl-D-aspartate (NMDA) receptor, the α-amino-3-hydroxy-5-methyl-4-
isoxazole propionic acid (AMPA) receptor, and the kainic acid receptor [7-10]. Furthermore, KYNA acts as an agonist of the G-protein-coupled receptor 35 (GPR35) and the aryl
hydrocarbon receptor (AHR) [11-14]. In addition, opioid receptors are presumed to be
interacting partners of KYNA [15,16].
It was previously postulated that the main component of KYNA-induced inhibition
in glutamatergic neurotransmission may attribute to non-competitive inhibition of α7-
nicotinic acetylcholine receptors at glutamatergic presynaptic axon terminals [17], thereby
regulating the release of glutamate. However, these results could not be reproduced by
four different, independent groups subsequently. Thus, it is still questionable that KYNA
may affect glutamate release via the mechanism [18-22]. KYNA plays crucial roles in the
regulation of the intracellular Ca2+ and mitochondrial dysfunction-induced neuronal cell
death in conditions associated with excitotoxicity (Fig. 1).
Figure 1. KYNA influences the neuronal and glial glutamatergic neurotransmission.
Recently, KYNA and its novel pharmacokinetically favorable analogues demonstrated beneficial effects in animal models of neurologic diseases including pathologic
pain sensation, migraine, ischemic stroke, and epilepsy, neurodegenerative diseases, and
psychiatric disorder including depression, anxiety, and addiction [23-39]. Accordingly,
neuroprotective KYN metabolites, their analogues, the inhibition of Trp-KYN enzymes
which are responsible for production of toxic metabolites, their use for biomarkers, and
its interaction with adjacent biosystems are under extensive research [40-48].
The beneficial effects were detected when these molecules were peripherally administered in an acute or semi-chronic manner with relatively high (millimolar) concentrations. Lower levels of KYNA were observed in patients with neurodegenerative diseases
and psychiatric disorders [3,6,32,49]. Those illnesses are generally characterized by alterations in inflammatory mediators and mu-opioid receptor, and increased levels in neurotoxic Try-KYN metabolites, which, furthermore, lead to changes in the amygdala [50].
However, Manipulations to elevate KYNA levels have a potential risk of interfering with
cognitive functions. Indeed, elevated levels of KYNA in the brain or its chronic application
in higher doses are known to evoke cognitive impairment by inhibiting predominantly
the glutamatergic system, a phenomenon having been linked to the pathophysiology of AD [51]. Furthermore, prenatal exposure of high levels of KYNA has also been experimentally shown to be associated with sustained cognitive deficits, with implications to
schizophrenia [52,53]. Therefore, it is essential to identify the doses of KYNA and KYNArelated molecules to provide neuroprotection without any associated cognitive side effects.
In humans, KYNA is robustly synthesized in the endothelium and its serum levels
correlate with homocysteine, a risk factor for cognitive decline: recent studies have suggested that a selective hippocampal increase of the KYNA level may be an important factor contributing to KYNA-related cognitive impairment. Identifying the mechanisms by
which high KYNA levels in the hippocampal area may contribute to the deterioration of
cognition would provide insight that might be used to manage inflammation-associated
mental health disorders, including the discovery of new diagnostic and treatment therapies for depression: recently, several studies have suggested the effectiveness of non-invasive brain simulation (NIBS) to interfere and modulate the abnormal activity of neural
circuits including the amygdala-mPFC-hippocampus, involved in the acquisition and
consolidation of memories, which are altered in psychiatric disorders, such as fear-related
disorder including anxiety disorder, phobias, posttraumatic stress disorder, or depression
[54,55].
Our previous studies did not detect any behavior impairment of animals when they
were treated intraperitoneally (i.p.) with millimolar doses of KYNA or its analogues
[23,56]. The administration of KYNA and its analogues increased inducibility of long-term
potentiation (LTP) in the CA1 region in rats, indicating better hippocampal function [57].
However, few data are available on the effects of a low dose KYNA. It was reported that
KYNA has a dose-dependent dual action on AMPA receptors: the nanomolar and micromolar concentrations of KYNA could facilitate the responses of AMPA receptors via
modulating their desensitization, whereas the millimolar doses of this compound antagonized these receptors [58].
It was demonstrated that KYNA was able to reduce the amplitudes of the field excitatory postsynaptic potentials (EPSPs) in hippocampal slices of young rats at micromolar
concentrations, whereas the nanomolar concentrations evoked stimulation. Therefore,
KYNA as a 'Janus-faced' molecule may display different effects according to its concentration by acting on different receptors and through mechanisms [59]. A lower endogenous formation of KYNA induce positive effects in the cognition. Indeed, the role of the
kynurenine aminotransferase II (KAT II), an enzyme responsible for the endogenous
KYNA synthesis in the human brain, has been recently emphasized in the mechanisms of
memory; activities of KAT I and II showed age-dependent increase with an exception for
KAT II in the frontal cortex, which could be related to functional alterations in the PFC
reported in psychiatric and brain-damaged patients’ memory and learning abilities. Furthermore, recent studies revealed that naturally occurring bilateral lesions in the human
ventromedial PFC compromise the capacity of associative learning [60,61], suggesting that
PFC dysfunctions cause impairment of aversive learning and emotional memory circuits,
which might be transversal across many psychiatric disorders in humans. Pharmacological inhibition or genetic ablation of KAT II reduced KYNA levels in the brain and improved the performance in working/spatial memory and sustained attention tasks in different animal models [62-64]. The inhibition of KAT II, with a subsequent reduction of an
endogenous KYNA level restores normal cognitive function and thus, a manipulation of
KYNA levels may be a promising therapeutic target in cognitive impairment associated
with elevated concentrations of KYNA in the brain.
Study: The association between gut microbiota and cognitive decline: A systematic review of the literature. Image credit: Toa55/Shutterstock.com
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