Faster Cognitive Decline Linked to Cumulative Physiologic Stress

 

With your massive stress from your incompetent doctor not having 100% recovery protocols maybe you want a better doctor. Or the proper solution; EXACT 100% RECOVERY PROTOCOLS! Will your replacement doctor at least get 100% recovery protocols going?

Faster Cognitive Decline Linked to Cumulative Physiologic Stress

Higher cumulative physiologic stress reflected in salivary  was associated with faster cognitive decline, a prospective study showed.

Older adults with high cumulative cortisol exposure had worse composite global cognition scores over time, reported Ted K. S. Ng, PhD, of Rush University Medical Center in Chicago, at the Alzheimer's Association International Conference. The findings were published in JAMA Network Open.

A moderate level of intra-day cortisol variability was associated with slower cognitive decline, Ng said. Black and white participants had different cortisol profiles at baseline, but associations between cortisol and cognitive decline were similar across racial groups.

"Our study suggests that how cortisol fluctuates across the day may provide important insights into cognitive aging," Ng noted.

"We examined five complementary indices capturing three key physiological dimensions of diurnal cortisol regulation -- intra-day variability, cumulative daily exposure, and diurnal change -- rather than relying on a single cortisol measure," he told MedPage Today. "We found that these different dimensions showed distinct relationships with cognitive aging, suggesting that different aspects of stress physiology may provide complementary insights."

Cortisol follows a circadian rhythm with a sharp post-awakening rise and a gradual decline across the day. It crosses the blood-brain barrier and binds receptors in regions critical for cognition.

Changes in hypothalamic-pituitary-adrenal (HPA) axis activity have been implicated in cognitive aging, Ng and colleagues noted. It's not clear how prospective associations between cortisol and cognitive outcomes may differ by race, they added.

The researchers followed 3,895 people in the Chicago Health and Aging Project for up to 11 years. The cohort included 2,503 Black and 1,392 white participants; the mean age was 77.

Participants provided three salivary cortisol samples across a single day (waking, afternoon, and bedtime) and had repeated cognitive assessments.

"A major strength of the study is its scale and diversity," Ng pointed out. "We studied nearly 4,000 community-dwelling older adults, including more than 60% women and more than 60% Black participants, making this one of the largest and most racially diverse population-based studies of salivary cortisol and cognitive aging."

All baseline cortisol indices were associated with cross-sectional cognitive performance. "Although Black participants had distinct baseline diurnal cortisol profiles, including a more blunted diurnal rhythm, the associations between cortisol indices and cognitive outcomes were broadly similar across Black and white participants," Ng said.

"This suggests that while patterns of diurnal cortisol may differ between populations, their relationships with cognitive aging may be broadly consistent," he added. "Further research is needed to better understand the factors underlying these baseline differences."

No significant associations between cortisol and incident Alzheimer's disease were seen over the follow-up period. "This likely reflects several factors, including the substantially smaller subset with adjudicated Alzheimer's disease, the relatively small number of incident cases, and the shorter follow-up relative to the long preclinical course of Alzheimer's disease," Ng noted.

"An alternative, and not mutually exclusive, interpretation is that alterations in diurnal cortisol patterning may be more informative as early physiological indicators of neurocognitive aging than of shorter-term clinical Alzheimer's disease incidence," he added.

The findings were based on a single day of cortisol sampling. Multi-day sampling may improve reliability of within-person variability and show longer-term HPA-axis dynamics, but a single-day protocol over multiple time points is commonly used in large epidemiologic studies, the researchers noted. The study also did not measure perceived stress.

"As stress-related health challenges have become increasingly important public health concerns, our findings reinforce the need to better understand how different aspects of stress physiology influence brain health over time," Ng said.

"Because salivary cortisol is non-invasive, relatively inexpensive, and feasible to collect repeatedly outside clinical settings, it represents a promising research tool for large-scale population studies investigating stress biology, brain health, and aging," he added.

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. Connect:

Faster Cognitive Decline Linked to Cumulative Physiologic Stress

 

With your massive stress from your incompetent doctor not having 100% recovery protocols maybe you want a better doctor. Or the proper solution; EXACT 100% RECOVERY PROTOCOLS! Will your doctor at least get 100% recovery protocols going?

Faster Cognitive Decline Linked to Cumulative Physiologic Stress

How cortisol fluctuates may provide insight into cognitive aging

Higher cumulative physiologic stress reflected in salivary cortisol was associated with faster cognitive decline, a prospective study showed.

Older adults with high cumulative cortisol exposure had worse composite global cognition scores over time, reported Ted K. S. Ng, PhD, of Rush University Medical Center in Chicago, at the Alzheimer's Association International Conference. The findings were published in JAMA Network Open.

A moderate level of intra-day cortisol variability was associated with slower cognitive decline, Ng said. Black and white participants had different cortisol profiles at baseline, but associations between cortisol and cognitive decline were similar across racial groups.

"Our study suggests that how cortisol fluctuates across the day may provide important insights into cognitive aging," Ng noted.

"We examined five complementary indices capturing three key physiological dimensions of diurnal cortisol regulation -- intra-day variability, cumulative daily exposure, and diurnal change -- rather than relying on a single cortisol measure," he told MedPage Today. "We found that these different dimensions showed distinct relationships with cognitive aging, suggesting that different aspects of stress physiology may provide complementary insights."

Cortisol follows a circadian rhythm with a sharp post-awakening rise and a gradual decline across the day. It crosses the blood-brain barrier and binds receptors in regions critical for cognition.

Changes in hypothalamic-pituitary-adrenal (HPA) axis activity have been implicated in cognitive aging, Ng and colleagues noted. It's not clear how prospective associations between cortisol and cognitive outcomes may differ by race, they added.

The researchers followed 3,895 people in the Chicago Health and Aging Project for up to 11 years. The cohort included 2,503 Black and 1,392 white participants; the mean age was 77.

Participants provided three salivary cortisol samples across a single day (waking, afternoon, and bedtime) and had repeated cognitive assessments.

"A major strength of the study is its scale and diversity," Ng pointed out. "We studied nearly 4,000 community-dwelling older adults, including more than 60% women and more than 60% Black participants, making this one of the largest and most racially diverse population-based studies of salivary cortisol and cognitive aging."

All baseline cortisol indices were associated with cross-sectional cognitive performance. "Although Black participants had distinct baseline diurnal cortisol profiles, including a more blunted diurnal rhythm, the associations between cortisol indices and cognitive outcomes were broadly similar across Black and white participants," Ng said.

"This suggests that while patterns of diurnal cortisol may differ between populations, their relationships with cognitive aging may be broadly consistent," he added. "Further research is needed to better understand the factors underlying these baseline differences."

No significant associations between cortisol and incident Alzheimer's disease were seen over the follow-up period. "This likely reflects several factors, including the substantially smaller subset with adjudicated Alzheimer's disease, the relatively small number of incident cases, and the shorter follow-up relative to the long preclinical course of Alzheimer's disease," Ng noted.

"An alternative, and not mutually exclusive, interpretation is that alterations in diurnal cortisol patterning may be more informative as early physiological indicators of neurocognitive aging than of shorter-term clinical Alzheimer's disease incidence," he added.

The findings were based on a single day of cortisol sampling. Multi-day sampling may improve reliability of within-person variability and show longer-term HPA-axis dynamics, but a single-day protocol over multiple time points is commonly used in large epidemiologic studies, the researchers noted. The study also did not measure perceived stress.

"As stress-related health challenges have become increasingly important public health concerns, our findings reinforce the need to better understand how different aspects of stress physiology influence brain health over time," Ng said.

"Because salivary cortisol is non-invasive, relatively inexpensive, and feasible to collect repeatedly outside clinical settings, it represents a promising research tool for large-scale population studies investigating stress biology, brain health, and aging," he added.

Salivary cortisol emerges as a potential early marker of cognitive aging

 Your competent? doctor needs to determine your cognitive baseline so any declines post stroke can be quickly addressed!

Salivary cortisol emerges as a potential early marker of cognitive aging

In a large prospective cohort of nearly 3,900 older adults followed for up to 11 years, altered daily cortisol patterns were associated with faster cognitive decline, although they were not linked to short-term Alzheimer's disease risk.

The findings, published in JAMA Network Open, suggest that salivary cortisol could serve as an early biomarker of neurocognitive aging and highlight racial differences in stress-related biological patterns that may inform future research and prevention strategies.

“In this cohort study examining salivary cortisol levels and cognitive decline, across the 5 salivary cortisol indices, distinct yet complementary patterns emerged that reflect distinct aspects of diurnal cortisol patterning and associations with cognitive decline,” wrote Ted K. S. Ng, PhD, Rush University Medical Center, Chicago, Illinois, and colleagues. “All indices were associated cross-sectionally with cognitive performance…when participants with the lowest 10% of baseline cognitive performance were excluded, mean cortisol remained significant, underscoring its robustness as an early physiological marker associated with subsequent cognitive decline among cognitively healthy adults.”

For the study, the researchers analysed data from 3,895 Black and White older adults (mean age, 76.7 years) enrolled in the Chicago Health and Aging Project, measuring salivary cortisol at waking, afternoon, and bedtime and following participants for cognitive outcomes over 11 years. Five cortisol indices reflecting daily hormone variability, cumulative exposure, and diurnal change were evaluated in relation to global cognition, cognitive decline, and incident Alzheimer's disease.

Higher cumulative cortisol exposure was associated with faster cognitive decline, with participants in the highest quintile of mean cortisol (β = -0.02; P = .02) and area under the curve (β = -0.02; P = .046) experiencing greater decline over time. In contrast, moderate-to-high intraday cortisol variability was associated with slower cognitive decline (Q3 β = 0.02; P = .04; Q4 β = 0.03; P = .003).

No cortisol measure was associated with incident Alzheimer's disease during follow-up.

Black participants exhibited lower overall cortisol exposure but flatter daily cortisol slopes and lower intraday variability than White participants, although the relationship between cortisol patterns and cognitive decline was similar across racial groups.

“Because cortisol patterns may be responsive to behavioural, pharmacologic, and social interventions, these findings underscore opportunities for precision prevention and equity-informed strategies targeting stress-related cognitive aging,” the authors wrote.

Reference: https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2851652

SOURCE: JAMA Network Open

The Top 10 Longevity Articles That Defined 2025 by Super Age

 I'm going to get there.

The Top 10 Longevity Articles That Defined 2025

AI Uncovers Hidden Stress Damage in the Body

 

With your massive stress from your incompetent? doctor not having 100% recovery protocols, have your competent? doctor CREATE EXACT 100% RECOVERY PROTOCOLS TO PREVENT THIS! Your doctor needs to exactly quantify the stress damage they are doing. So ask your 'professional' to measure this. Oh, your doctor can't do that? Incompetence runs rampant in the stroke medical world, so you'll have to scour the world!

AI Uncovers Hidden Stress Damage in the BodyAI Uncovers Hidden Stress Damage in the Body

Summary: Researchers developed an AI tool that detects chronic stress by measuring adrenal gland volume on routine chest CT scans. This biomarker aligns with cortisol levels, stress questionnaires, and future cardiovascular outcomes, offering the first imaging-based method to quantify stress load in the body.

The findings show that larger adrenal volume is linked to higher stress, greater allostatic load, and increased risk of heart failure and mortality. Because millions of CT scans are already performed each year, this approach could transform early stress detection and prevention without requiring new tests or radiation.

Key Facts

• AI Stress Biomarker: Adrenal gland volume measured from CT scans reflects long-term chronic stress more reliably than momentary cortisol tests.
• Risk Prediction: Higher adrenal volume is linked to elevated cortisol, increased allostatic load, and greater risk of future heart failure.
• Clinical Potential: This biomarker can be extracted from routine imaging, offering a scalable tool for early stress-related disease prevention.

Source: RSNA

Using a deep learning AI model, researchers identified the first-of-its-kind biomarker of chronic stress detectable through routine imaging, according to research being presented next week at the annual meeting of the Radiological Society of North America (RSNA).

Chronic stress can affect both physical and psychological well-being, causing a variety of problems including anxiety, insomnia, muscle pain, high blood pressure and a weakened immune system, according to the American Psychological Association. Research shows that chronic stress can contribute to the development of major illnesses, such as heart disease, depression and obesity.

The study’s lead author, Elena Ghotbi, M.D., a postdoctoral research fellow at Johns Hopkins University School of Medicine in Baltimore, Maryland, developed and trained a deep learning model to measure adrenal gland volume on existing CT scans.

Each year, tens of millions of chest CT scans are performed in the United States alone.

“Our approach leverages widely available imaging data and opens the door to large-scale evaluations of the biological impact of chronic stress across a range of conditions using existing chest CT scans,” Dr. Ghotbi said.

“This AI-driven biomarker has the potential to enhance cardiovascular risk stratification and guide preventive care without additional testing or radiation.”

Senior author Shadpour Demehri, M.D., professor of radiology at Johns Hopkins, said chronic stress is a prevalent condition or complaint that many adults deal with on a daily basis.

“For the first time, we can ‘see’ the long-term burden of stress inside the body, using a scan that patients already get every day in hospitals across the country. Until now, we haven’t had a way to measure and quantify the cumulative effects of chronic stress, other than questionnaires, surrogate serum markers like chronic inflammation, and cortisol measurement, which is very cumbersome to obtain.” Dr. Demehri said.

Unlike single cortisol measurements, which provide a momentary snapshot of stress levels, adrenal volume acts like a biological barometer of chronic stress.

In the study, the researchers obtained data on 2,842 participants (mean age 69.3; 51% women) from the Multi-Ethnic Study of Atherosclerosis, a comprehensive study combining chest CT scans, validated stress questionnaires, cortisol measures and markers of allostatic load—the cumulative physiological and psychological effects of chronic stress on the body. This rare integration of imaging, biochemical and psychosocial data made it the optimal, and likely only, cohort for developing an imaging biomarker of chronic stress.

The researchers retrospectively applied their deep learning model to the CT scans to segment and calculate the volume of the adrenal glands. Adrenal Volume Index (AVI) was defined as volume (cm³) divided by height² (m²). Salivary cortisol was collected eight times per day over two days. Allostatic load was based on body mass index, creatinine, hemoglobin, albumin, glucose, white blood count, heart rate and blood pressure.

Statistical associations were assessed between AVI and cortisol, allostatic load, and psychosocial stress measures, including depression and perceived stress questionnaires. The researchers found that AI-derived AVI correlated with validated stress questionnaires, circulating cortisol levels and future adverse cardiovascular outcomes.

Higher AVI was associated with greater cortisol, peak cortisol and allostatic load. Participants with high perceived stress had higher AVI compared to those with low stress. AVI was also associated with a higher left ventricular mass index. Each 1 cm³/m² increase in AVI was linked to greater risk of heart failure and mortality.

“With up to 10-year follow-up data on our participants, we were able to correlate AI-derived AVI with clinically meaningful and relevant outcomes,” Dr. Ghotbi said.

“This is the very first imaging marker of chronic stress that has been validated and shown to have an independent impact on a cardiovascular outcome, namely, heart failure.”

“For over three decades, we’ve known that chronic stress can wear down the body across multiple systems,” said Teresa E. Seeman, Ph.D., study co-author and professor of epidemiology at UCLA and a pioneering researcher in stress and health.

“What makes this work so exciting is that it links a routinely obtained imaging feature, adrenal volume, with validated biological and psychological measures of stress and shows that it independently predicts a major clinical outcome. It’s a true step forward in operationalizing the cumulative impact of stress on health.”

Dr. Demehri said that by linking an easily measurable imaging feature with multiple validated indicators of stress and downstream disease, this research introduces an entirely new, practical way to quantify chronic stress.

“The key significance of this work is that this biomarker is obtainable from CTs that are performed widely in United States for various reasons,” Dr. Demehri said. “Secondly, it is a physiologically sound measure of adrenal volume, which is part of the chronic stress physiologic cascade.”

The researchers said the imaging biomarker could be used in a variety of diseases that are associated with chronic stress in middle-aged and older adults.

Other co-authors are Roham Hadidchi, Seyedhouman Seyedekrami, Quincy A. Hathaway, M.D., Ph.D., Michael Bancks, Nikhil Subhas, Matthew J. Budoff, M.D., David A. Bluemke, M.D., Ph.D., R. Graham Barr and Joao A.C. Lima, M.D.

Key Questions Answered:

Q: What did researchers discover about chronic stress?

A: They identified the first imaging-based biomarker of chronic stress using adrenal gland volume measured by AI.

Q: Why is adrenal volume important?

A: It reflects long-term physiological stress, correlating with cortisol, allostatic load, and future cardiovascular risk.

Q: What makes this method different from cortisol tests?

A: Cortisol fluctuates throughout the day; adrenal volume offers a stable, cumulative indicator of long-term stress burden.

Editorial Notes:

• This article was edited by a Neuroscience News editor.
• Journal paper reviewed in full.
• Additional context added by our staff.

About this AI and stress research news

Author: Linda Brooks
Source: RSNA
Contact: Linda Brooks – RSNA
Image: The image is credited to Neuroscience News

Original Research: The findings will be presented at the 111th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA).

High cortisol levels associated with greater risk of death from COVID-19, levels are high after stroke

You don't want to get COVID-19 in the first week after your stroke. Ask your doctor how they are rapidly reducing cortisol levels after your stroke. 

Are these in your doctors protocol?

13 proven natural ways to lower cortisol - Medical News Today

Cortisol Levels and the Severity and Outcomes of Acute Stroke: A Systematic Review 

This paragraph from there:

Cortisol levels were high in the first week after stroke in the majority of studies (26 studies, n = 1,340). Higher cortisol was associated with dependency (8/11 studies, n = 822), delirium (5/6 studies, n = 269) depression (3/5 studies n = 117) and mortality (8/10 studies, n = 856). Five studies adjusted for stroke severity; one found an association between higher cortisol and dependency, and three found an association between higher cortisol and mortality. Cortisol levels are high for at least 7 days after stroke. Elevated cortisol after stroke is associated with dependency, morbidity, and mortality; however, there is insufficient evidence to conclude that these relationships are independent of stroke severity. 

The latest here:

High cortisol levels associated with greater risk of death from COVID-19

COVID-19 patients with extremely high levels of the stress hormone cortisol in their blood are more likely to deteriorate quickly and die, according to new research published today.

The study, led by NIHR Research Professor Waljit Dhillo from Imperial College London and Consultant Endocrinologist at Imperial College Healthcare NHS Trust, provides the first data to show that cortisol levels are a marker of the severity of the illness. The researchers suggest they can be used to identify those patients who are more likely to need intensive care.
Cortisol is produced by the body in response to stress such as illness, triggering changes in metabolism, heart function and the immune system to help our bodies cope. Our cortisol levels when healthy and resting are 100-200 nm/L and nearly zero when we sleep.
When ill patients have low levels of cortisol, it can be life threatening. Excessive levels of cortisol during illness can be equally dangerous, leading to increased risk of infection and poor outcomes. In the new observational study of 535 patients, of whom 403 were confirmed to have COVID-19, cortisol levels in patients with COVID-19 were significantly higher than in those without. The levels in the COVID-19 group ranged as high as 3241—considerably higher even than after major surgery, when levels can top 1000.
Amongst the COVID-19 patients, those with a baseline cortisol level of 744 or less survived on average for 36 days. Patients with levels over 744 had an average survival of just 15 days.
Professor Dhillo, Head of Division of Diabetes, Endocrinology and Metabolism at Imperial College London, said: "From an endocrinologist's perspective, it makes sense that those COVID-19 patients who are the sickest will have higher levels of cortisol, but these levels are worryingly high.
"Three months ago when we started seeing this wave of COVID-19 patients here in London hospitals, we had very little information about how to best triage people. Now, when people arrive at hospital, we potentially have another simple marker to use alongside oxygen saturation levels to help us identify which patients need to be admitted immediately, and which may not. Having an early indicator of which patients may deteriorate more quickly will help us with providing the best level of care as quickly as possible, as well as helping manage the pressure on the NHS. In addition, we can also take cortisol levels into account when we are working out how best to treat our patients."
The study, published in The Lancet Diabetes & Endocrinology and funded by the National Institute for Health Research (NIHR) and the Medical Research Council, involved 535 patients admitted to three London hospitals—Charing Cross, Hammersmith and St Mary's—with suspected COVID-19 between 09 March and 22 April 2020. A COVID-19 swab test and routine blood tests—including a baseline measurement of cortisol levels—were performed within 48hrs of admission.
Over the study period, just under 27 per cent of the COVID-19 group died during the study period compared to just under 7per cent of the non-COVID-19 group.
Professor Dhillo and his team hope that their findings can now be validated in a larger scale clinical study.

Why Marijuana Compounds Could Eventually Replace Anti-Anxiety Meds

And you have a lot of anxiety because your doctor is telling you nothing about how to get 100% recovered.
https://www.forbes.com/sites/daviddisalvo/2017/08/29/why-marijuana-compounds-could-eventually-replace-anti-anxiety-meds/#271fba89191b
By

David DiSalvo , Contributor

Research into the potential medical uses of marijuana compounds continues apace. Among the most recent, a study delved into why marijuana is an effective stress reducer. While not conclusive on their own, the results contribute to a longer-term possibility – that marijuana compounds may turn out to be more effective and safer in alleviating anxiety than prescription anxiety meds.
The recent study focused on marijuana’s potency in reducing the stress response in regular users. Stress was measured by tracking cortisol amounts in study participants’ saliva. Cortisol, the “stress hormone,” is a reliable indicator of stress; higher or lower amounts correlate closely with a person’s response to stressful situations.
The study compared the stress responses of a group of daily marijuana users to a group of non-users. The results were consistent: regular users had a “blunted” response to acute stress. In effect, their internal stress engines had been tuned down by regular exposure to marijuana.

“To the best of our knowledge, this is the first study to examine the effects of acute stress on salivary cortisol levels in chronic cannabis users compared to non-users,” said Carrie Cuttler, study co-author and clinical assistant professor of psychology. “While we are not at a point where we are comfortable saying whether this muted stress response is a good thing or a bad thing, our work is an important first step in investigating potential therapeutic benefits of cannabis at a time when its use is spreading faster than ever before.”
The comment that this result is too preliminary to be called “a good or a bad thing” is well-taken (tuning down the stress response too much is likely to have both negatives and positives), but it does point to the potential for harnessing a modified version of this effect down the road.
These results pair well with findings from research showing that marijuana compounds have a distinct effect on levels of the neurotransmitter GABA, which plays a key role in the anxiety response. GABA is an inhibitory neurotransmitter that acts as a brake on anxiety, counterbalancing the effects of excitatory brain chemicals like glutamate. Early research suggests that compounds in marijuana, particularly cannabidiol (CBD), enhance GABA’s effects with moderate downsides. (CBD has an impressive research profile in several areas, anxiety among them.)
Benzodiazepines, the mostly commonly used prescription anxiety meds, also affect GABA levels. The meds are effective at quickly delivering what users are seeking – an anxiety extinguishing calmness.
But that benefit comes at a cost. Tolerance to benzodiazepines, including Xanax and Klonopin, builds rapidly, requiring a user to take more and more of the meds to get the same effect. It doesn’t take long to develop a dependency that may not end. Instead of going through the well-documented hell of getting off the meds, many users choose to stay on them indefinitely. In addition, benzo side effects—fatigue, disorientation and mental fogginess, among others—are notoriously difficult to manage while trying to make it through the day. Overdose potential for benzos is also high, accounting for thousands of deaths in the U.S. every year.
While preliminary, the latest research suggests that the compounds in marijuana could eventually be harnessed to deliver anxiety relief with decreased dependency, fewer side effects and less overdose potential.
The early signs are promising, but this, like all possibilities for future medical uses of marijuana compounds, depends on the research continuing.
The latest study was published in journal Psychopharmacology.
 

Gut microbes may talk to the brain through cortisol

With this from Feb. 2017 and the new research, what protocol is your doctor following to improve your stroke recovery?

Restoring gut bacteria to youthful age linked to improved stroke recovery in mice

Feb. 2017

Gut microbes may talk to the brain through cortisol

University of Illinois College of Agricultural, Consumer and Environmental Sciences

IMAGE: University of Illinois doctoral student Austin Mudd examines piglet brain images. view more 

Credit: Stephanie Henry

URBANA, Ill. - Gut microbes have been in the news a lot lately. Recent studies show they can influence human health, behavior, and certain neurological disorders, such as autism. But just how do they communicate with the brain? Results from a new University of Illinois study suggest a pathway of communication between certain gut bacteria and brain metabolites, by way of a compound in the blood known as cortisol. And unexpectedly, the finding provides a potential mechanism to explain the characteristics of autism.
"Changes in neurometabolites during infancy can have profound effects on brain development, and it is possible that the microbiome -- or collection of bacteria, fungi, and viruses inhabiting our gut -- plays a role in this process," says Austin Mudd, a doctoral student in the Neuroscience Program at U of I. "However, it is unclear which specific gut bacteria are most influential during brain development and what factors, if any, might influence the relationship between the gut and the brain."
The researchers studied 1-month-old piglets, which are remarkably similar to human infants in terms of their gut and brain development. They first identified the relative abundances of bacteria in the feces and ascending colon contents of the piglets, then quantified concentrations of certain compounds in the blood and in the brain.
"Using the piglet as a translatable animal model for human infants provides a unique opportunity for studying aspects of development which are sometimes more difficult or ethically challenging to collect data on in human infants," Mudd says. "For example, in this study we wanted to see if we could find bacteria in the feces of pigletsthat might predict concentrations of compounds in the blood and brain, both of which are more difficult to characterize in infants."
The researchers took a stepwise approach, first identifying predictive relationships between fecal bacteria and brain metabolites. They found that the bacterial genera Bacteroides and Clostridium predicted higher concentrations of myo-inositol, Butyricimonas positively predicted n-acetylaspartate (NAA), and Bacteroides also predicted higher levels of total creatine in the brain. However, when bacteria in the genus Ruminococcus were more abundant in the feces of the piglets, NAA concentrations in the brain were lower.
"These brain metabolites have been found in altered states in individuals diagnosed with autism spectrum disorder (ASD), yet no previous studies have identified specific links between bacterial genera and these particular metabolites," Mudd notes.
The next step was to determine if these four bacterial genera could predict compounds in the blood. "Blood biomarkers are something we can actually collect from an infant, so it's a clinically relevant sample. It would be nice to study an infant's brain directly, but imaging infants is logistically and ethically difficult. We can, however, obtain feces and blood from infants," says Ryan Dilger, associate professor in the Department of Animal Sciences, Division of Nutritional Sciences, and Neuroscience Program at U of I.
The researchers found predictive relationships between the fecal microbiota and serotonin and cortisol, two compounds in the blood known to be influenced by gut microbiota. Specifically, Bacteroides was associated with higher serotonin levels, while Ruminococcus predicted lower concentrations of both serotonin and cortisol. Clostridium and Butyricimonas were not associated strongly with either compound.
Again, Mudd says, the results supported previous findings related to ASD. "Alterations in serum serotonin and cortisol, as well as fecal Bacteroides and Ruminococcus levels, have been described in ASD individuals."
Based on their initial analyses, the researchers wanted to know if there was a three-way relationship between Ruminococcus, cortisol, and NAA. To investigate this further, they used a statistical approach known as "mediation analysis," and found that serum cortisol mediated the relationship between fecal Ruminococcus abundance and brain NAA concentration. In other words, it appears that Ruminococcus communicates with and makes changes to the brain indirectly through cortisol. "This mediation finding is interesting, in that it gives us insight into one way that the gut microbiota may be communicating with the brain. It can be used as a framework for developing future intervention studies which further support this proposed mechanism," Dilger adds.
"Initially, we set out to characterize relationships between the gut microbiota, blood biomarkers, and brain metabolites. But once we looked at the relationships identified in our study, they kept leading us to independently reported findings in the autism literature. We remain cautious and do not want to overstate our findings without support from clinical intervention trials, but we hypothesize that this could be a contributing factor to autism's heterogenous symptoms," Mudd says. Interestingly, in the time since the researchers wrote the paper, other publications have also reported relationships between Ruminococcus and measures of brain development, supporting that this might be a promising area for future research.
Dilger adds, "We admit this approach is limited by only using predictive models. Therefore, the next step is to generate empirical evidence in a clinical setting. So it's important to state that we've only generated a hypothesis here, but it's exciting to consider the progress that may be made in the future based on our evidence in the pre-clinical pig model."

###

The article, "Serum cortisol mediates the relationship between fecal Ruminococcus & brain N-acetylaspartate in the young pig," is published in Gut Microbes [DOI: 10.1080/19490976.2017.1353849]. Mudd and Dilger's co-authors include Kirsten Berding, Mei Wang, and Sharon Donovan from the Division of Nutritional Sciences and the Department of Food Science and Human Nutrition at U of I. The study was supported by Mead Johnson Nutrition.

Our senses can’t learn under stress

You are under considerable stress since your doctor knows NOTHING about getting you to 100% recovery. Is that stress contributing to your lack of recovery? A very simple question for your doctor to answer, not dodge the question.
http://www.alphagalileo.org/ViewItem.aspx?ItemId=171513&CultureCode=en
Stress is part of our everyday lives – while some thrive on it, it makes others sick. But what does stress do to our senses?
When we train them, we can sharpen our senses thereby improve our perceptual performance. The stress hormone cortisol completely blocks this important ability. In the current issue of “Psychoneuroendocrinology” neuroscientists of the Ruhr University Bochum (RUB) report on this finding.
“Previous research has already shown that stress can prevent the retrieval of memories. But now we have discovered that it also has a major effect on our perception and perceptual learning,” explains Dr Hubert Dinse, one of the authors of the study.
Tactile sense in training
In their study, researchers investigated how the sense of touch of 30 study participants could be changed after a training phase. Half of them received a medium dose of the stress hormone cortisol, while the other half received a placebo drug.
To make training comparable across all participants, the researchers employed the well-established approach of passive finger stimulation. Previous studies and several therapy approaches have shown that this method leads to an improved tactile acuity.
Tactile performance was assessed using the so-called “two-point discrimination threshold”. This marker indicates how far apart two stimuli need to be, to be discriminated as two separate sensations – the closer they are, the better the sense of touch.
No learning effect after cortisol
The placebo group improved their tactile acuity, as expected, by about 15 percent. In contrast, the cortisol given to the other group blocked almost all the stimulation-induced improvement. Cognitive psychologist Prof Dr Oliver T. Wolf explains:” Our data show that a single dose of cortisol not only disrupts memory in the hippocampus, but it also has a substantial effect on the plasticity of sensory areas of the brain.”
Cortisol blocks synaptic connections
In previous studies on a cellular level, neuroscientists have demonstrated that cortisol suppresses the strengthening of synaptic connections, and therefore the plasticity of the brain – its ability to learn. The team led by Hubert Dinse therefore suggests, their results could also explain by cortisol-induced suppression of synaptic plasticity.
Effects on clinical treatments
The results of the study could also affect clinical treatments. Corticosteroids, of which cortisol is one, are often used in the treatment of immunological and neurological diseases. However, the effects on perceptual learning observed in this study may counteract rehabilitation efforts, which rely on just these mechanisms. It is therefore necessary to find out which effects the clinical treatment with these substances has on learning mechanisms in the brain.
Funding
Scientists from the fields of neuroinformatics and cognitive psychology, as well as from the Neurological Clinic Bergmannsheil collaborated on this research project. They were all funded by a grant to Collaborative Research Centre 874 from the German Research Foundation (Deutsche Forschungsgemeinschaft, DFG).
http://news.rub.de/english/press-releases

• Full bibliographic informationHubert R. Dinse, Jan-Christoph Kattenstroth, Melanie Lenz, Martin Tegenthoff, Oliver T. Wolf (2016) The stress hormone cortisol blocks perceptual learning in humans, Psychoneuroendocrinology 77: 63-67, DOI: doi: 10.1016/j.psyneuen.2016.12.002
  Link to publication: http://www.sciencedirect.com/science/article/pii/S0306453016305315