Daily social connections may improve long-term health and cognition

 My social connections are not pushed aside.

(Sunday is music at Red Cedar, Tuesday is music at Moriarties, Thursday is trivia at Moriarties; all are bars, so alcohol is involved, there will be no condemnations of that.) All part of my plan to exponentially expand my social connections to prevent dementia. 

Did your incompetent? doctor fail to get you recovered enough to easily initiate these again?

Daily social connections may improve long-term health and cognition

Calling a friend after a long day. Showing up to a neighbor's dinner when you'd rather stay home. Lingering a little longer in a conversation that didn't need to last. Such ordinary, even trivial, moments. But to psychologist Susan Charles, Associate Dean of Graduate Programs in the School of Social Ecology, they may be among the most consequential health decisions a person makes.

Charles has been awarded a $2,550,958 grant from the National Institute on Aging to investigate how the daily rhythms of feeling socially connected, or disconnected, shape the way our bodies and minds hold up over time.

Her project, "Linking Daily Dynamics of Social Connection to Physical and Cognitive Functioning," could fundamentally change how doctors, therapists and public health officials approach loneliness and social isolation.

The health stakes of feeling connected

Most people intuitively understand that having close relationships is good for them. Decades of research confirmed it. But, Charles argues that science has been limited by looking at social connection in only one way - as a fixed trait, a general level of sociability that a person either has or doesn't have.

Our understanding of social connection and its strong association with health is based largely on studies assessing social experiences using static, trait-like measures of general levels of thoughts and activities. Yet, feeling socially connected varies from day to day, fluctuating as much as other commonly recognized daily emotional experiences."

Susan Charles, Associate Dean of Graduate Programs, School of Social Ecology, University of California - Irvine

In other words, the same person who feels warmly surrounded by community on Tuesday might feel profoundly alone by Thursday.

Charles believes such fluctuations may hold the key to understanding how social life gets under our skin, quite literally.

She draws a vivid picture of what this might look like in an ordinary life.

"Daily decisions to call a friend, or to go to a social function even though you are tired from a long day at work may not seem like health decisions," Charles says, "but these times of social connection influence well-being."

The effects, she explains, are both immediate and cumulative. A shared laugh can ease distress and trigger feelings of safety and contentment. Showing up for a regular dinner with a neighbor means you leave your house, stay physically active and engage in the kind of conversation that demands mental effort - tracking information, forming arguments, retrieving memories. Over time, those moments compound.

"Consistent positive social connection enhance health, affecting myriad health outcomes from physical symptoms to gene expression," Charles adds.

Small daily changes, she points out, have the potential to create a "ripple effect" that contributes to longer-term outcomes - for better or for worse.

To test these ideas, Charles is turning to one of the most extraordinary longitudinal datasets in social science: the Midlife in the United States study, known as MIDUS.
The project draws on two longitudinal daily diary datasets spanning nearly 20 years. In one dataset, participants completed nightly phone interviews every day for a week, across three separate waves in 2002, 2014, and 2023. A second dataset captures two waves of daily diary data spanning about a decade, with waves beginning in 2012 and 2023.

Altogether, the study follows more than 2,900 adults ranging in age from 24 to 97.

In addition to the daily diary interviews, participants completed extensive surveys, underwent cognitive assessments and some even flew to a medical facility where they provided blood and urine samples, completed physical fitness tasks and submitted to a battery of biomarker testing.

"Any single facet of this study is interesting to study," Charles says, "but together we have an unprecedented view into how their daily lives unfold and are related to multiple measures of cognitive, physical and mental health."

Charles will delve deep in her search for evidence of social connection's effects.

The professor and her research team plan to examine cortisol, often called the "stress hormone," with chronically high levels linked to cognitive decline and poor physical health.

Charles also will analyze inflammatory markers, gene expression profiles, and even biomarkers of biological age acceleration - measures of how fast a person's cells are aging relative to their chronological age.

The biological story she hopes to tell connects the social world to a phenomenon scientists call "inflammaging," the age-related increase in chronic low-grade inflammation now understood to play a central role in multiple health conditions, including cardiovascular disease, diabetes, certain forms of dementia and arthritis.

"We will examine biomarkers that have been related to poorer health - chronically high inflammation, high levels of cortisol, and gene expression related to inflammation and viral load - and see how these biomarkers are related to the levels and consistency of daily social connection," Charles explains.

If daily patterns of feeling connected, or disconnected, can be shown to move those biological needles, the implications for preventive medicine could be substantial.

Why age changes everything

The study's age range: from young adults in their mid-20s to nonagenarians. Charles is particularly interested in how the relationship between social connection and health shifts as the body grows more vulnerable.

"We know from nearly 100 years of research that social connections are vitally important for people of all ages," she says. "In this study, we are particularly interested in how patterns of social connection change over time in later life, and how social connections may vary in their relationship with health among people with less robust physical systems."

As chronic illness and functional disability become more prevalent with age, she argues, the stakes of social isolation grow higher - and so does the potential benefit of meaningful daily connection.

The United States Surgeon General has called loneliness and social isolation a public health epidemic, and the COVID-19 pandemic accelerated trends toward isolation that were already underway.

Against that backdrop, Charles sees her study as doing something more than documenting a problem. She wants to change the conversation around it.

"Our research reframes a message from warning people about the risks of social isolation to acknowledging the power of positive social connections," she says. "We will be examining different contexts to reveal when and under what circumstances social connections increase our health."

Her goal is simple but potentially transformative: to make social connection a recognized daily health behavior, as concrete and actionable as exercise or diet.

"Social connection should be listed as a daily health behavior for everyone," Charles says. "Every finding that links social connection to better physical and cognitive functioning will reinforce and strengthen this message, as well as identify those most at risk for both social isolation and for the health risk of lack of social connection."

Source:

University of California - Irvine

Gut microbiome shifts may begin before Alzheimer’s symptoms appear

 Then have your competent? doctor test for this so THOSE EXACT PREVENTION PROTOCOLS CAN BE INITIATED! Don't have any, do they? PURE INCOMPETENCE! 

Why you need them;

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 

Gut microbiome shifts may begin before Alzheimer’s symptoms appear

A new review traces how diet, gut bacteria, and their metabolites may intersect with the silent biological changes that precede cognitive decline.

Want to read later? Download your PDF copy by clicking here.

In a recent narrative review published in the journal Nutrients, researchers across Australia summarized evidence on the gut microbiota, microbial metabolites, and dietary patterns in relation to early Alzheimer’s disease (AD). The review did not generate or analyze new data.

AD has a long preclinical stage when metabolic alterations, amyloid accumulation, and neuroinflammation develop while people remain cognitively unimpaired (CU). Understanding these biological changes can help elucidate mechanisms pertinent to early prevention. Recent findings suggest that early AD pathology may be accompanied by alterations in the gut microbiota and other systemic changes. Diet plays an important role in gut microbiota composition and metabolic output.

Diet-induced changes in the microbiota may influence gut–brain communication relevant to metabolic and neuroinflammatory regulation. Research also links long-term dietary patterns to the risk of cognitive impairment and AD. Nevertheless, the relevance of microbiome–diet interactions to microbial functional pathways in preclinical AD remains poorly defined. In this narrative review, researchers summarized evidence linking the gut microbiota, microbial metabolites, and diet to early AD.

AD: Diagnosis and Therapeutic Context

Research advances have enabled AD detection based on biological markers without relying solely on clinical symptoms. Cerebrospinal fluid (CSF) biomarkers and amyloid positron emission tomography (PET) imaging enable the detection of pathology in CU individuals. Standardized amyloid PET quantification, such as the Centiloid scale, can help stratify people along the preclinical continuum and facilitate comparisons across studies.

Current AD treatments offer limited benefit once cognitive decline is established. Common symptomatic treatments, including memantine, donepezil, galantamine, and rivastigmine, provide modest cognitive and functional improvements. Further, while disease-modifying therapies, for example, lecanemab, have been developed for early-stage AD, they are restricted to select populations and have limited clinical benefit.

As such, most available treatments are initiated only after substantial damage has occurred, thereby reducing their capacity to meaningfully modify disease progression. This therapeutic limitation constitutes a substantial challenge in AD treatment, underscoring the need for further research and attention toward earlier AD stages.

Gut–Brain Communication

The gut–brain axis (GBA) is the bidirectional communication network between the central nervous system (CNS) and the gastrointestinal system. It plays an important role in regulating physiological processes, including brain function, metabolism, and immune activity. Alterations in the microbiota composition can modify metabolic and inflammatory conditions in ways that may increase vulnerability to neurodegenerative processes.

Microbial metabolites are an important component of gut–brain communication. Short-chain fatty acids (SCFAs), the most studied metabolites, regulate immune cell differentiation, metabolic pathways, epithelial barrier integrity, and cytokine production. SCFAs can modulate neuronal function and neuroinflammatory processes through these actions. Emerging evidence suggests that GBA disruptions may contribute to the metabolic and inflammatory disturbances seen in early AD. However, direct human evidence in preclinical AD remains limited, and SCFA effects may depend on their concentration and biological context.

Gut Microbiome Dysregulation in AD

A growing body of research suggests that AD is associated with changes in gut microbiota function and composition. In particular, reduced abundance of SCFA-producing genera, such as Eubacterium, Roseburia, and Faecalibacterium, has been commonly reported in AD and cognitive impairment. Meanwhile, some studies report an increased relative abundance of Escherichia/Shigella and other Proteobacteria, which are associated with inflammatory signaling, metabolic imbalance, and oxidative stress.

Microbiota functional alterations in AD include disruptions in fermentation pathways, changes in lipid and amino acid metabolism, and decreases in SCFA biosynthesis. Early changes in microbial metabolic pathways and SCFA-producing taxa have been reported in a small number of studies involving CU individuals with biomarker evidence of amyloid pathology. Although studies have reported inconsistent findings, they suggest that the earliest stages of AD may be characterized by gut microbial dysregulation.

Dietary Patterns Associated With AD

Dietary Approaches to Stop Hypertension (DASH) and the Mediterranean diet (MD) are associated with improved cognitive, cardiovascular, and metabolic outcomes in aging populations. Both emphasize increased intake of plant-based foods, while limiting processed and red meats, added sugars, and saturated fats. Higher adherence to these diets is linked to reduced cerebral amyloid burden, slower cognitive decline, and improved vascular function in older individuals.

The Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet, which combines elements from DASH and MD, has similarly been associated with slower accumulation of AD-related pathology. Further, the prudent dietary pattern has been associated with improved inflammatory and metabolic profiles in aging populations. It is characterized by high intake of fruits, whole grains, vegetables, fish, low-fat dairy, and legumes. The prudent dietary pattern has been associated with higher microbial diversity and enrichment of SCFA-producing taxa.

Concluding Remarks

Collectively, available research suggests that alterations in the composition and metabolic activity of the gut microbiota may be associated with early AD pathology. Reductions in SCFA-producing taxa and alterations in microbial metabolic pathways have been observed in a limited number of studies involving CU populations with amyloid pathology.

However, the current evidence base has important limitations. Most studies have involved populations with AD or mild cognitive impairment rather than biomarker-confirmed preclinical AD, and much of the available evidence is cross-sectional, preventing conclusions about the direction of the relationship. Sequencing has generally been limited to the genus level, while few studies have jointly assessed diet, gut microbiota, microbial functional pathways, SCFAs, and amyloid pathology. As a narrative review, this work also focused primarily on SCFAs rather than other potentially relevant microbial metabolites.

Future studies should prioritize longitudinal, species-level metagenomic analyses in CU individuals grouped by amyloid status. These studies should assess microbial functional pathways, SCFAs, and diet within the same cohort. Researchers should also investigate fecal microbiota transplantation as a potential intervention in experimental AD models.

Journal reference:

• Dissanayaka DMS, Rainey-Smith SR, Sohrabi HR, et al. (2026). Gut Microbiome Changes in Preclinical Alzheimer’s Disease. Nutrients, 18(15):2469. DOI: 10.3390/nu18152469. https://www.mdpi.com/2072-6643/18/15/2469

3D Human Brain Tissue Model Replicates Alzheimer’s Pathology

 Now our stroke researchers CAN EXACTLY MODEL how a stroke causes dementia! Then they can create protocols that prevent that dementia from happening! But nothing will occur; THERE IS NO LEADERSHIP OR STRATEGY IN STROKE ANYPLACE! Don't have a stroke is their answer. 

3D Human Brain Tissue Model Replicates Alzheimer’s Pathology

Summary: Researchers introduced a highly reproducible three-dimensional human brain tissue model capable of replicating complex neurodegenerative processes in Alzheimer’s disease. Developed over nine years using human stem cells, the self-organizing tissue spheroids integrate functional neurons, astrocytes, and microglial immune cells into micro-architectures the size of half a pinhead.

The engineered tissue model faithfully expresses key Alzheimer’s-relevant genes and proteins, forms functional synaptic networks, and exhibits active microglial surveillance. The team demonstrated the platform’s clinical relevance by inducing characteristic amyloid beta aggregates and subsequently dissolving them using newly approved therapeutic antibodies.

Key Facts

• Tri-Culture Cellular Interplay: Unlike traditional two-dimensional cultures, the 3D spheroid model incorporates neurons forming functional synapses, astrocytes providing metabolic support, and microglial immune cells performing active tissue surveillance.
• Rapid Self-Organization: Driven by a proprietary differentiation cocktail and nutrient medium, differentiated stem cells assemble and self-organize into functional mini-tissue spheroids within one week.
• Transcriptomic & Proteomic Fidelity: Comprehensive testing confirmed that all primary genes and proteins associated with Alzheimer’s pathology and cell-to-cell signaling are fully active within the engineered tissues.
• Validation via Plaque Dissolution: The researchers successfully triggered human amyloid beta aggregate formation within the tissue spheroids and verified that current anti-amyloid Alzheimer’s therapeutics, mediated by active microglia, successfully cleared the pathology.
• Robotic Automation & Industrial Scaling: The laboratory is currently adapting the platform for automated robotic manufacturing to produce thousands of identical, diseased tissue spheroids for large-scale industrial drug testing.

Source: LMU

How can Alzheimer’s research be made faster, better, and more effective? After decades of intensive research worldwide and despite recent therapeutic advances, scientists have not managed to fully arrest the progress of the disease.

“What we are still lacking is three-dimensional models that accurately replicate the complex interactions in human brain tissue with Alzheimer’s disease,” explains Dominik Paquet, Professor of Neurobiology at the Institute for Stroke and Dementia Research at LMU University Hospital.

Researchers bioengineered a 3D human brain tissue model containing neurons, astrocytes, and microglia that successfully replicates Alzheimer’s amyloid clearance and supports automated drug screening. Credit: Neuroscience News

This is precisely the area in which his team has now made major progress – with potentially far-reaching consequences for the development of new drugs against Alzheimer’s disease.

The group reported the exciting new results in the journal Nature Neuroscience.

For laypeople, it always seems a bit like magic when researchers take stem cells and grow tissues that resemble the human original. According to Dominik Paquet, however, it takes a mixture of scientific creativity, technical skills, and patience: “It took us nine years,” says the neuroscientist, “to develop our new, three-dimensional model of human brain tissue before it worked at all necessary levels.”

What does he mean by all necessary levels, we might ask? For Alzheimer’s research, the interaction of different cell types and their biochemical functions are the most important thing – much more so than the exact replication of the structure of the brain.

The right recipe for genuine interplay

The starting material for the new 3D tissue model is human stem cells, which can be converted into various brain cell types – in this case, neurons, astrocytes, and microglial cells. To obtain this set, the stem cells have to be treated with a cocktail of different substances “according to a very specific recipe we developed.”

In a special nutrient solution, Paquet continues, the differentiated cells connect and adhere to each other. “Within a week, they form little tissue balls about the size of half a pinhead. These spheroids self-organize and take on key functions of the brain.”

Almost everything just like in a real human brain

Their neurons form extensions and connect with functional synapses. The astrocytes supply their neighbors with nutrients. And the microglial cells – the immune cells of the brain – monitor their environment and ensure that no dead cells or foreign matter that does not belong there can accumulate. “We also tested whether all genes and proteins that are important for the study of Alzheimer’s disease are active in our tissue model,” says the neuroscientist. “And that was indeed the case.

Reproducible, modifiable – and disease-relevant

Another major advantage of the system is its reproducibility. That is to say, if you follow the instructions of the Munich researchers, you will reliably obtain tissue structures with the same composition and the same functions.

“However, we can also modify the generated brain tissue from the outside,” says Dominik Paquet. “For example, we can trigger symptoms of a disease like Alzheimer’s, test potential drugs, and so forth.” In fact, the researchers have successfully induced the formation of the Alzheimer’s-typical amyloid aggregates – and then dissolved them again with new drugs that are already available. The microglia that play a key role in the disease were demonstrably active in the process.

Next step: automation for efficient drug development

“Our system,” says Dominik Paquet, “could help accelerate the development of new drugs.”

With this goal in mind, his team is currently working on automating and scaling the manufacture of the tissue models using robots. This would mean manufacturing hundreds or even thousands of tissues with the same disease symptoms. This is particularly important for applications in industrial-scale medicine – for example, to be able to efficiently test many new substances in a human system for their effectiveness against Alzheimer’s.

Key Questions Answered:

Q: Why are three-dimensional tissue models better than traditional cell cultures for Alzheimer’s research?

A: Traditional 2D cell cultures grow flat on plastic dishes and lack the complex structural interactions, spatial organization, and multi-cell communication found in a living brain. The 3D spheroid model brings neurons, astrocytes, and microglia together in a spatial framework that allows microglial immune cells to actively clear dead cells and pathology just as they would in human brain tissue.

Q: What specific brain cell types are included in the new LMU Munich tissue model?

A: The model uses human stem cells differentiated into three primary cell populations: neurons (which build functional synaptic connections), astrocytes (which support cell metabolism and structure), and microglia (the resident immune cells responsible for monitoring brain health and clearing toxic protein aggregates).

Q: How does this development accelerate the discovery of new Alzheimer’s drugs?

A: Because the system is highly reproducible and being adapted for robotic automation, pharmaceutical companies will be able to manufacture thousands of standardized human brain tissue models exhibiting Alzheimer’s symptoms. This allows researchers to test thousands of potential drug candidates rapidly in a realistic human cellular environment before moving to animal or clinical trials.

Editorial Notes:

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

About this Alzheimer’s disease research news

Author: Dominic Anders
Source: LMU
Contact: Dominic Anders – LMU
Image: The image is credited to Neuroscience News

Experts urge reaction time training to cut senior fall risk

 Is this a part of your rehab protocols? NO, so incompetent everything in your stroke hospital!

Experts urge reaction time training to cut senior fall risk

1. Experts urge reaction time training to cut senior fall risk

Why reaction time matters: Slower reactions with age raise fall risk and limit independence, but targeted training can improve both safety and cognitive health.

Simple drills work: Experts recommend tennis ball catches, whistle cues, and dual-task balance games to sharpen reflexes without special equipment.

Broader health benefits: Improved reaction time supports mobility, confidence, and brain function, potentially lowering dementia risk and extending active years.

References

5 ways to improve reaction time as you age, according to an OT | Verywell Health
Why reaction-time training should be part of your exercise routine as you get older | WPTZ Plattsburgh-Burlington
This overlooked physical skill matters more than you think for longevity | The Healthy
How long should you be able to stand on one leg after 60? What your balance says about your health | Health
Essential reaction time drills to help prevent falls in older adults | Men's Journal
6 unconventional balance exercises that challenge your brain, too | Parade

2. CDC identification of falls as leading cause of injury-related death in adults over 65

The U.S. Centers for Disease Control and Prevention (CDC) identifies falls as the top cause of injury-related death among adults aged over 65. This highlights the significant health risk falls pose to the senior population.

References

5 ways to improve reaction time as you age, according to an OT | Verywell Health
Why reaction-time training should be part of your exercise routine as you get older | WPTZ Plattsburgh-Burlington
This overlooked physical skill matters more than you think for longevity | The Healthy
How long should you be able to stand on one leg after 60? What your balance says about your health | Health

3. Annual fall-related injuries treated among older adults in the United States

Millions of older adults in the United States are treated annually for injuries resulting from falls. These injuries represent a major public health concern alongside fall-related deaths.

References

This overlooked physical skill matters more than you think for longevity | The Healthy
How long should you be able to stand on one leg after 60? What your balance says about your health | Health
Why reaction-time training should be part of your exercise routine as you get older | WPTZ Plattsburgh-Burlington

4. Examples of situations requiring quick reaction in older adults

Situations such as tripping or navigating traffic demand rapid processing and response to avoid injury. These scenarios illustrate the practical importance of maintaining quick reaction times in daily life for seniors.

References

5 ways to improve reaction time as you age, according to an OT | Verywell Health

5. Impact of slow reaction time on fall likelihood

Slow reaction time increases the likelihood of falling among older adults. This physical limitation can impair the ability to respond quickly to loss of balance or environmental hazards.

References

5 ways to improve reaction time as you age, according to an OT | Verywell Health
Why reaction-time training should be part of your exercise routine as you get older | WPTZ Plattsburgh-Burlington
Essential reaction time drills to help prevent falls in older adults | Men's Journal
This overlooked physical skill matters more than you think for longevity | The Healthy
How long should you be able to stand on one leg after 60? What your balance says about your health | Health

6. Targeting reaction speed, balance, strength, and aerobic capacity to reduce fall risk

By improving reaction speed alongside balance, strength, and aerobic capacity, older adults may reduce their risk of falling and related health complications. This multifaceted approach addresses both physical and functional aspects of fall prevention.

References

This overlooked physical skill matters more than you think for longevity | The Healthy
How long should you be able to stand on one leg after 60? What your balance says about your health | Health

7. Examples of reaction-time training drills for older adults

Reaction-time training drills for older adults include exercises such as catching a dropped tennis ball, responding to directional whistle cues, and combining balance activities with mental tasks. These activities are designed to mimic real-life unpredictability and stimulate faster nervous system responses. They can be performed alone or with a partner to suit different training environments.

References

Essential reaction time drills to help prevent falls in older adults | Men's Journal
Why reaction-time training should be part of your exercise routine as you get older | WPTZ Plattsburgh-Burlington

8. Combining Balance Exercises with Mental Tasks

Some drills combine physical balance challenges with simultaneous mental tasks, such as solving a problem or recalling information. This dual-task approach engages both the body and brain, enhancing coordination and cognitive processing under physical strain.

References

Essential reaction time drills to help prevent falls in older adults | Men's Journal
6 unconventional balance exercises that challenge your brain, too | Parade

A common dietary nutrient feeds a gut pathway linked to atrial fibrillation

Have your competent? doctor decipher this since choline is helpful in brain health and reducing your dementia risk. Your doctor better know of all these 17 research articles! OR COMPLETE FUCKING INCOMPETENCE!

• choline (17 posts to October 2011)

 A common dietary nutrient feeds a gut pathway linked to atrial fibrillation

A 5,090-person cohort and complementary mouse experiments trace how a diet-linked microbial pathway could reshape atrial structure, electrical activity, and autonomic control.

Study: Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction. Image Credit: Lightspring / Shutterstock

Want to read later? Download your PDF copy by clicking here.

A recent study published in The Journal of Clinical Investigation suggests that trimethylamine N-oxide (TMAO), produced when gut microbes convert nutrients such as choline into trimethylamine (TMA), which is then oxidized in the liver, is independently associated with prevalent atrial fibrillation (AF) in humans and may promote AF susceptibility, onset, and progression in mice. By inhibiting muscarinic receptor 2 signaling, TMAO may disrupt autonomic regulation, with increased sympathetic tone proposed as one mechanism contributing to AF. These findings suggest that diet, through its effects on the gut microbiome and TMAO production, may influence AF susceptibility, although dietary effects were tested only in mice, and the human findings came from a cardiovascular referral cohort.

AF remains a major contributor to cardiovascular disease (CVD)-related illness and death worldwide. Elevated TMAO levels have been associated with CVD-related changes, including cardiac fibrosis and inflammation. However, the biological mechanisms through which TMAO may promote AF remain unclear. An improved understanding of the gut microbiome-related changes that influence AF development could help researchers develop more targeted treatments to reduce the global burden of AF and CVD. Future studies will need to determine whether therapeutic strategies targeting TMAO can safely reduce AF and how differences in gut microbiome composition, liver metabolism, and kidney filtration affect circulating TMAO levels.

About the study

In the present study, researchers investigated whether TMAO generated through the gut microbiome could promote AF development. To do so, they quantified TMAO, choline, and betaine levels in plasma samples obtained from 5,090 individuals from the Cleveland Clinic GeneBank who were undergoing elective cardiac catheterization, using liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS/MS). Individuals with a myocardial infarction during the preceding four weeks or elevated troponin I at enrollment were excluded.

The team also used genetically engineered mice expressing the CREM-IbΔC-X variant of the human cyclic adenosine monophosphate (cAMP) response element modulator gene to investigate AF development. These animals received TMAO- or choline-supplemented diets in separate experiments. The researchers conducted transesophageal electrical pacing studies to determine AF inducibility among wild-type C57BL/6J mice fed TMAO-supplemented or standard diets. They placed electrodes in the esophagus of the animals to deliver electrical impulses and promote arrhythmias in the heart. They separately used serial needle-electrode electrocardiograms (ECGs) to monitor the first onset of paroxysmal AF and progression to persistent AF, defined as AF detected across 10 consecutive ECG recordings, in CREM-IbΔC-X mice receiving different diets, with wild-type mice included in separate control experiments.

The team also explored the effects of iodomethylcholine (IMC), a selective inhibitor of choline trimethylamine-lyase (CutC/D), on TMAO levels. They analyzed microbial DNA from cecal samples, used echocardiography to assess the effects of choline and IMC on cardiac structure, and performed cardiac electrical mapping to examine the electrophysiological effects of choline supplementation. They exposed human and murine cardiac cells, including fibroblasts and cardiomyocytes, to physiologically relevant TMAO levels and examined interleukin-1β (IL-1β) and NLRP3 expression. They also performed murine ECG experiments using MCC950, a chemical compound that inhibits the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome.

The researchers used logistic regression to estimate odds ratios (ORs) for prevalent AF. The models accounted for variables such as age, sex, smoking habits, comorbidities, and laboratory findings, including high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR).

Results

The team found that plasma TMAO, betaine, and choline levels were independently and significantly associated with AF prevalence. For TMAO, the adjusted odds ratio comparing the highest with the lowest concentration tertile was 1.7 (95% confidence interval, 1.3-2.1). The TMAO- or choline-supplemented CREM-IbΔC-X mice developed AF earlier than chow-fed controls, without significant differences in body mass or appreciable liver-related pathologies.

Viva Saliva Book: The ultimate guide to saliva Book preview Download eBook Compilation of the top interviews, articles, and news in the last year.Download the latest edition

The genetically modified animals also showed higher plasma TMAO levels after choline supplementation. These findings suggest that TMAO may contribute to AF onset and progression in mice, and that reducing gut microbial production of TMAO may help lower AF susceptibility in this model. Mice fed TMAO diets showed an increased likelihood of developing AF in the transesophageal pacing study. In fact, mice receiving TMAO supplementation showed an 11-fold increase in AF inducibility in both sexes compared with controls.

Choline supplementation altered the structure and function of the heart. Left atrial size was significantly increased at five and eight weeks, while IMC treatment attenuated the enlargement at eight weeks. In choline-supplemented mice, optical mapping revealed a nonsignificant reduction in conduction velocity but significantly shortened action-potential duration at 80% repolarization and reduced cardiac wavelength. In HEK293 cells engineered to express muscarinic receptor 2 (M2R), TMAO inhibited receptor signaling in the presence of the M2R agonist carbachol. Together with higher heart rates in choline-fed mice, this finding supported a possible role for autonomic dysfunction in promoting AF, although sympathetic activity was not directly measured.

While choline accelerated AF onset, IMC treatment delayed the onset of paroxysmal and persistent AF and reduced TMAO levels by suppressing the microbial conversion of choline to TMA under both aerobic and anaerobic conditions, thereby reducing subsequent TMAO formation in the liver. Choline altered gut microbial communities in association with AF. IMC, on the other hand, attenuated these changes by reversing the loss of gut microbiome diversity and reducing the choline-associated increase in overall Firmicutes abundance, although individual species showed differing patterns. An exploratory analysis also linked Parvibacter caecicola to the timing of paroxysmal AF onset in mice, although the authors noted that this association requires further investigation. TMAO also did not increase NLRP3 or IL-1β expression at physiologically relevant concentrations, and MCC950 did not delay AF development, suggesting that NLRP3 inflammasome activation was not a major mechanism in this mouse model.

Conclusions

The findings demonstrate that higher plasma TMAO levels were independently associated with prevalent AF in humans, whereas direct TMAO exposure or gut microbial production of TMA from dietary choline promoted AF onset and progression in mouse models. However, the human analysis was observational and assessed existing rather than incident AF, while the mechanistic and therapeutic findings came from mice and cell experiments. No human dietary or IMC intervention was tested, and AF recurrence following IMC withdrawal was not examined.

Together, the preclinical findings support clinical investigation of TMAO-lowering approaches as potential strategies for AF prevention. In future studies, researchers should explore different molecules that can reduce TMAO levels and determine how gut microbiome composition, hepatic FMO3 activity, and renal clearance influence circulating TMAO levels and treatment responses in humans.

Journal reference:

• Arjunan, S. et al. (2026). Gut microbial trimethylamine N-oxide generation promotes risk of atrial fibrillation via muscarinic receptor-mediated autonomic dysfunction. The Journal of Clinical Investigation. DOI: 10.1172/JCI201684, https://www.jci.org/articles/view/201684

Are All “Healthy Diets” Equal for Stroke Prevention?

 Impossible to tell since none are objective and have EXACT PROTOCOLS!

Are All “Healthy Diets” Equal for Stroke Prevention?

• Anel Karisik, MD

Castro-Barquero S, Rimm EB, Jovin TG, Martínez-González MA, Salas-Salvadó J, Corella D, Arós F, Serra-Majem L, Fitó M, Pintó X, et al. Adherence to Different Dietary Patterns and Subsequent Risk of Total, Ischemic, and Hemorrhagic Stroke. Stroke. 2026;57:945–956.

Eating healthy is supposed to protect the heart — but do all "heart-healthy" dietary patterns protect equally well against stroke? A new analysis from the PREDIMED trial takes on this question and delivers surprisingly clear answers. Castro-Barquero et al. compared four widely promoted dietary patterns — Mediterranean, DASH, MIND, and the Planetary Health Diet — in over 7,000 high-risk individuals over a median follow-up of 4.3 years. The result: Those participants in the highest quintile of cumulative adherence had approximately 75% lower stroke risk than those in the lowest quintile. For DASH and the Planetary Health Diet, only non-significant trends emerged.

 

The MIND diet combines Mediterranean principles with a focus on brain health — and performs on par with classic Mediterranean eating. One possible explanation is that these dietary patterns share several components, including plant-based foods, olive oil, and nuts. That said, caution is warranted. Because this was a post hoc observational analysis of adherence within a randomized trial, causal inference regarding the dietary scores themselves remains limited. Those with higher dietary adherence were also generally healthier and more physically active; residual confounding cannot be ruled out. Only 135 stroke events were available for analysis, which limits statistical power, particularly for subgroup comparisons. And the cohort consisted of older, high-risk individuals in Spain, which constrains generalizability.

Nevertheless, this study strengthens the case for Mediterranean and MIND dietary patterns in stroke prevention, without the differences between diet scores being over-interpreted. The real message remains simple: Overall dietary quality appears important, but in this cohort, the strongest evidence supported Mediterranean and MIND dietary patterns.

How Many Push-Ups Should You Be Able to Do at Your Age?

 The chart doesn't go past age 69 so I'm obviously good at doing none. All because my doctor was A COMPLETE FUCKING FAILURE AT CURING MY HAND SPASTICITY!

How Many Push-Ups Should You Be Able to Do at Your Age?

Note: Women completed the assessment from the modified, knees-on-the-ground position, and ACE didn’t assess people over 69 years old. If you’re in that group, the goal shifts from hitting a benchmark to holding onto what you’ve got — strength training at least twice a week helps preserve muscle. 

Age	Men: Excellent	Men: Room to Improve	Women: Excellent	Women: Room to Improve
20-29	36 or more	16 or fewer	30 or more	9 or fewer
30-39	30 or more	11 or fewer	27 or more	7 or fewer
40-49	25 or more	9 or fewer	24 or more	4 or fewer
50-59	21 or more	6 or fewer	21 or more	1 or fewer
60-69	18 or more	4 or fewer	17 or more	1 or fewer