A new study led by Mount Sinai researchers reports that commonly used cardiac screening methods fail to identify almost half of the people who are actually at risk of having a heart attack. The findings were released on November 21 in a brief report in the Journal of the American College of Cardiology: Advances. According to the authors, the results point to a significant weakness in current prevention practices because today’s guidelines may overlook individuals who would benefit from earlier detection and protective treatment.
The team evaluated the accuracy of the widely used atherosclerotic cardiovascular disease (ASCVD) risk score and a newer tool known as PREVENT. PREVENT incorporates additional variables and is designed to offer a broader picture of cardiovascular risk alongside screening for symptoms.
Risk Scores Often Underestimate Individual Danger
“Our research shows that population-based risk tools often fail to reflect the true risk for many individual patients,” says corresponding author Amir Ahmadi, MD, Clinical Associate Professor of Medicine (Cardiology) at the Icahn School of Medicine at Mount Sinai. “If we had seen these patients just two days before their heart attack, nearly half would NOT have been recommended for further testing or preventive therapy guided by current risk estimate scores and guidelines.”
Dr. Ahmadi adds that relying heavily on risk assessments and symptom reports may not be the best strategy for prevention. “This study suggests that the current approach of relying on risk scores and symptoms as primary gatekeepers for prevention is not optimal,” he says. “It may be time to fundamentally reconsider this model and move toward atherosclerosis imaging to identify the silent plaque — early atherosclerosis- before it has a chance to rupture.”
How ASCVD and PREVENT Are Used in Routine Care
In everyday practice, physicians calculate a person’s ASCVD risk score during routine primary care visits, typically for adults aged 40 through 75 who do not have known heart disease. The score estimates the likelihood of a heart attack or stroke within 10 years by factoring in age, sex, race, blood pressure, cholesterol, diabetes, and smoking. Results from the ASCVD or PREVENT calculators guide decisions about preventive therapy, including whether to start statins.

Cardiologists also use these scores to help determine treatment. Patients with intermediate or high scores are usually offered cholesterol-lowering medication and sometimes additional diagnostic testing. Individuals with low or borderline scores, particularly if they report no chest pain or shortness of breath, are frequently reassured and discharged without further evaluation. The study found, however, that if patients who ultimately had their first heart attack had been assessed two days before the event, nearly half would have been classified as low or borderline risk by ASCVD, and more than half would have been categorized that way by PREVENT.
Study Examined Nearly 500 Patients With First Heart Attacks
To examine how well current tools perform, the researchers conducted a retrospective review of 474 patients younger than 66 who had no known coronary artery disease. All were treated for their first heart attack at Mount Sinai Morningside or The Mount Sinai Hospital between January 2020 and July 2025. Investigators collected demographic information, medical history, cholesterol levels, blood pressure readings, and the timing of symptoms such as chest pain or shortness of breath. Each patient’s 10-year ASCVD risk score was calculated, and the team simulated how the patient would have been evaluated two days before their heart attack. Patients were sorted into four categories: low (under 5 percent), borderline (5-7.5 percent), intermediate (7.5-20 percent), and high (more than 20 percent).
Symptoms Appear Too Late for Effective Prevention
The analysis focused on two areas: which patients would have qualified for preventive measures based on their score, and when symptoms began. Overall, 45 percent of patients would not have been recommended for preventive therapy or further diagnostic testing under ASCVD-based guidelines. This proportion rose to 61 percent when PREVENT was used. In addition, most patients (60 percent) noticed symptoms fewer than two days before their heart attack. This pattern shows how often symptoms emerge only when the disease has already advanced. The combined findings reveal a serious gap in prevention: people who appear healthy according to standard assessments may already have significant and silent atherosclerosis. Because of this, depending solely on symptoms and risk calculators can delay detection until meaningful prevention is no longer possible.
Researchers Call for Earlier Detection of Silent Plaque
“When we look at heart attacks and trace them backwards, most heart attacks occur in patients in the low or intermediate risk groups. This study highlights that a lower risk score, along with not having classic heart attack symptoms like chest pain or shortness of breath, which is common, is no guarantee of safety on an individual level,” says first author Anna Mueller, MD, an internal medicine resident at the Icahn School of Medicine at Mount Sinai. “Our study exposes a major flaw where tools effective for tracking large populations fall short when guiding individualized care. Instead, doctors should shift their focus from detecting symptomatic heart disease to detecting the plaque itself for earlier treatment, which could save lives.”
The researchers note that more work is needed to refine these methods, and future studies should explore ways to improve early identification and prevention approaches, including the use of cardiovascular imaging.

Researchers at the Paul Scherrer Institute PSI have clarified how spermine – a small molecule that regulates many processes in the body’s cells – can guard against diseases such as Alzheimer’s and Parkinson’s: it renders certain proteins harmless by acting a bit like cheese on noodles, making them clump together. This discovery could help combat such diseases. The study has now been published in the journal Nature Communications.ngs could contribute to new ways of tackling these brain disorders. The study has been published in the journal Nature Communications.As people live longer, age-related disorders, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, are becoming more common. These conditions are driven by harmful buildups in the brain made of misfolded amyloid proteins. These protein structures form long, thin fibers that resemble strands of spaghetti. So far, there is no effective treatment that can reliably prevent or clear these protein deposits.Spermine as a natural protector in cells and animalsA naturally occurring molecule in the body called spermine is offering new hope. In laboratory experiments, a team led by Jinghui Luo at the Center for Life Sciences at the Paul Scherrer Institute PSI showed that spermine can extend the lifespan of small nematode worms, improve their movement as they age, and strengthen their cellular power plants, the mitochondria. The researchers saw that spermine supports the body’s immune system in removing nerve-damaging amyloid protein deposits.These new results may form the foundation for developing new therapeutic strategies for diseases such as Alzheimer’s and Parkinson’s.Spermine is essential for the functioning of the organism. It belongs to a group of relatively small organic molecules known as polyamines. Spermine was first identified more than 150 years ago and named after seminal fluid, where it is present in particularly high concentrations. However, it is also found in many other cell types throughout the body, especially in cells that are active and capable of dividing.Gene regulation and biomolecular condensationSpermine supports cell movement and activity and is involved in many different cellular processes. One of its main roles is to interact with the nucleic acids in the genome, helping regulate which genes are switched on and how they are translated into proteins. This regulation ensures that cells can grow, divide, and eventually die in a controlled manner. Spermine is also crucial for a cellular process called biomolecular condensation. In this process, large molecules such as proteins and nucleic acids separate and gather into droplet-like regions inside the cell, creating small reaction hubs where important biochemical reactions take place.In the context of neurodegenerative disorders such as Alzheimer’s and Parkinson’s, earlier work had already suggested that spermine can protect nerve cells and ease age-related memory problems. What was missing until now was a clear picture of how spermine influences the harmful processes in nerve cells in a way that could be used for medical benefit.Helping cells clear toxic protein wasteLuo’s research group has now examined these mechanisms in greater depth. In addition to optical microscopy, the scientists used a method called SAXS scattering at PSI’s Swiss Light Source SLS to investigate the molecular dynamics of the processes involved. They studied these effects both in glass capillaries (in vitro) and in living organisms (in vivo). For the living system, they used the nematode C. elegans as a model organism.Their experiments showed that spermine causes harmful proteins to come together and form clumps through biomolecular condensation. This behavior supports a routine cellular cleanup process known as autophagy. In autophagy, damaged or unnecessary proteins are enclosed in small membrane-bound vesicles and then broken down safely by enzymes, effectively recycling cellular components.”Autophagy is more effective at handling larger protein clumps,” says study leader Luo. “And spermine is, so to speak, the binding agent that brings the strands together. There are only weakly attractive electrical forces between the molecules, and these organise them but do not firmly bind them together.”The entire process, Luo explains, can be imagined like a plate of spaghetti. “The spermine is like cheese that connects the long, thin noodles without gluing them together, making them easier to digest.”From kitchen metaphor to future therapiesSpermine also appears to play a role in other diseases, including cancer. Further research is needed to understand the underlying mechanisms in these conditions, after which spermine-based treatments could become realistic options. Alongside spermine, many other polyamines also perform important tasks in the body and are therefore of medical interest. This makes the field highly promising for future research. “If we better understand the underlying processes,” says Luo, “we can cook tastier and more digestible dishes, so to speak, because then we’ll know exactly which spices, in which amounts, make the sauce especially tasty.”AI and advanced imaging accelerate spermine researchArtificial intelligence is also being used in this search, because it can calculate promising combinations of “ingredients for the sauce” much more quickly on the basis of all available data. Luo also points out that time-resolved scattering measurements and high-resolution imaging, which can capture these processes in real time down to the subcellular level, are crucial for this work and for future studies. Outside of PSI, such advanced methods are available at only a few other synchrotron facilities worldwide.
Researchers at the Paul Scherrer Institute PSI have clarified how spermine – a small molecule that regulates many processes in the body’s cells – can guard against diseases such as Alzheimer’s and Parkinson’s: it renders certain proteins harmless by acting a bit like cheese on noodles, making them clump together. This discovery could help combat such diseases. The study has now been published in the journal Nature Communications.
Our life expectancy keeps rising – and as it does, age-related illnesses, including neurodegenerative diseases such as Alzheimer’s and Parkinson’s, become increasingly common. These diseases are caused by accumulations in the brain of harmful protein structures consisting of incorrectly folded amyloid proteins. Their shape is reminiscent of fibres or spaghetti. To date, there is no effective therapy to prevent or eliminate such accumulations.
Yet a naturally occurring molecule in the body called spermine offers hope. In experiments, researchers led by study leader Jinghui Luo, in the Center for Life Sciences at the Paul Scherrer Institute PSI, have discovered that this substance is capable of extending the life span of small nematode worms, improving their mobility in old age, and strengthening the powerhouses of their cells – the mitochondria. Specifically, the researchers observed how spermine helps the body’s immune system eliminate nerve-damaging accumulations of amyloid proteins.
The new findings could serve as a basis for developing novel therapies for such diseases.
A central mediator of cellular processes
Spermine is a vital substance for the organism. It belongs to the so-called polyamines, which are relatively small organic molecules. Spermine, first discovered more than 150 years ago, is named after the seminal fluid, as it is found in particularly high concentrations there. But it also occurs in many other cells of the body – especially those that are active and capable of dividing.

Spermine promotes cell mobility and activity and controls numerous processes. Above all, it interacts with the nucleic acids of the genome, regulating the expression of genes and their conversion into proteins. This ensures that cells can properly grow and divide and ultimately die. Spermine is also central to an important cellular process called biomolecular condensation: In this process, certain macromolecules, such as proteins and nucleic acids, segregate and collect within the cell in a droplet-like form, so that important reactions can take place there.
In connection with neurodegenerative diseases such as Alzheimer’s or Parkinson’s, there has previously been evidence that spermine can protect nerve cells and alleviate age-related memory loss. Lacking until now, however, has been a more precise understanding of how spermine intervenes in nerve-damaging processes – understanding that might make it possible to derive medical benefits from it.
Assisting cellular waste removal
Jinghui Luo’s group has now investigated this in more detail. In addition to optical microscopy, the researchers also used the SAXS scattering technique at PSI’s Swiss Light Source SLS to shed light on the molecular dynamics of these processes. The investigations were conducted both in a glass capillary (in vitro) and in a living organism (in vivo). The nematode C. elegans served as a model organism.
It was shown that spermine causes the harmful proteins to gather and, in a sense, clump together through biomolecular condensation. This facilitates a process called autophagy, which occurs routinely in our cells: Damaged or unnecessary proteins are wrapped up in small membrane vesicles and safely degraded with enzymes – a natural recycling process, in effect.
“Autophagy is more effective at handling larger protein clumps,” says study leader Luo. “And spermine is, so to speak, the binding agent that brings the strands together. There are only weakly attractive electrical forces between the molecules, and these organise them but do not firmly bind them together.”
The whole thing, says Luo, can also be imagined like a plate of spaghetti. “The spermine is like cheese that connects the long, thin noodles without gluing them together, making them easier to digest.”

Wanted: the right combination of ingredients
Spermine also exerts an influence on other diseases, including cancer for example. Here too research is needed to clarify the mechanisms at work – then spermine-based therapeutic approaches would be conceivable. In addition to spermine, there are many other polyamines that fulfil important functions in the organism and thus are medically interesting. Therefore research in this area has a lot of potential. “If we better understand the underlying processes,” says Luo, “we can cook tastier and more digestible dishes, so to speak, because then we’ll know exactly which spices, in which amounts, make the sauce especially tasty.”
Artificial intelligence is also being used in this search, because it can calculate promising combinations of “ingredients for the sauce” much more quickly on the basis of all available data. Luo also notes that time-resolved scattering measurement techniques and high-resolution imaging, which can depict such processes in real time and down to the subcellular level, are also important for this and subsequent studies. Apart from PSI, such methods are available at only a few other synchrotron facilities in the world.

Biomedical researchers at Texas A&M University report that they may have found a way to halt, or even reverse, the loss of cellular energy that comes with damage and aging. If future studies confirm the results, the discovery could lead to major changes in how many diseases are treated across medicine.
Dr. Akhilesh K. Gaharwar and Ph.D. student John Soukar, together with colleagues in the Department of Biomedical Engineering, have created a technique that supplies injured cells with fresh mitochondria. By replenishing these tiny energy producers, the method can restore energy output to previous levels and greatly improve the overall health of the cells.
Mitochondrial decline has been tied to aging, heart disease and several neurodegenerative conditions. A strategy that strengthens the body’s natural capacity to replace worn-out mitochondria could, in principle, help address all of these problems at once.
As human cells grow older or are harmed by degenerative disorders such as Alzheimer’s disease, or by exposure to harmful agents like chemotherapy drugs, their ability to generate energy steadily drops. A key reason is the shrinking number of mitochondria, the small, organ-like structures inside cells that supply most of the energy a cell uses. Whether in brain tissue, heart muscle or other organs, a decrease in mitochondria leads to weaker, less healthy cells that eventually can no longer perform their essential roles.
Nanoflowers Turn Stem Cells Into Mitochondria Donors
The research, published in Proceedings of the National Academy of Sciences, combined microscopic, flower-shaped particles called nanoflowers with stem cells. When stem cells were exposed to these nanoflowers, they began producing about twice as many mitochondria as usual. When the strengthened stem cells were then placed next to damaged or aging cells, they passed along their extra mitochondria to these neighboring, injured cells.
Once supplied with new mitochondria, the previously damaged cells were able to restore their energy production and normal activity. These revived cells not only showed improved energy levels but also became more resistant to cell death, even when they were later exposed to damaging treatments such as chemotherapy.

“We have trained healthy cells to share their spare batteries with weaker ones,” said Gaharwar, a professor of biomedical engineering. “By increasing the number of mitochondria inside donor cells, we can help aging or damaged cells regain their vitality — without any genetic modification or drugs.”
Although cells are naturally capable of exchanging small amounts of mitochondria, the nanoflower-treated stem cells, which the team describes as mitochondrial bio factories, transferred two to four times more mitochondria than untreated stem cells.
“The several-fold increase in efficiency was more than we could have hoped for,” said Soukar, lead author of the paper. “It’s like giving an old electronic a new battery pack. Instead of tossing them out, we are plugging fully-charged batteries from healthy cells into diseased ones.”
Making Mitochondria Therapies Last Longer
Researchers have tried other ways to increase the number of mitochondria inside cells, but these approaches often come with tradeoffs. Drug-based methods rely on small molecules that leave cells relatively quickly, so patients may need frequent and repeated treatments to maintain the effect. In contrast, the larger nanoparticles (which are roughly 100 nanometers in diameter) remain inside the cell and continue to stimulate mitochondria production more effectively. As a result, therapies based on this nanoflower technology might only need to be administered about once a month.
“This is an early but exciting step toward recharging aging tissues using their own biological machinery,” Gaharwar said. “If we can safely boost this natural power-sharing system, it could one day help slow or even reverse some effects of cellular aging.”
Molybdenum Disulfide Nanoparticles in Biomedical Use

The nanoflowers are made from molybdenum disulfide, an inorganic compound that can form many different two-dimensional shapes at very small scales. The Gaharwar Lab is among a small number of research groups investigating how molybdenum disulfide might be used for biomedical purposes.
Stem cells already play a central role in cutting-edge work on tissue repair and regeneration. Using nanoflowers to increase the performance of stem cells could mark an important step in making these cells even more effective in future therapies.
Versatile Approach for Many Tissues
One of the most promising aspects of the technique is its flexibility. Although the method is still in early stages and requires much more testing, it could theoretically be used to treat loss of function in many different tissues throughout the body.
“You could put the cells anywhere in the patient,” Soukar said. “So for cardiomyopathy, you can treat cardiac cells directly — putting the stem cells directly in or near the heart. If you have muscular dystrophy, you can inject them right into the muscle. It’s pretty promising in terms of being able to be used for a whole wide variety of cases, and this is just kind of the start. We could work on this forever and find new things and new disease treatments every day.”
The project received financial support from the National Institutes of Health, the Welch Foundation, the Department of Defense, and the Cancer Prevention and Research Institute of Texas. Additional backing came from the President’s Excellence Fund at Texas A&M University and the Texas A&M Health Science Center Seedling Grant. Key collaborators included Texas A&M researchers Dr. Irtisha Singh, Dr. Vishal Gohil, and Dr. Feng Zhao.

A large 20-year investigation following nearly 11,000 adults in Bangladesh found that reducing arsenic in drinking water was tied to as much as a 50 percent drop in deaths from heart disease, cancer and several other chronic illnesses. The research offers the strongest long-term evidence so far that lowering arsenic exposure can reduce mortality, even for people who lived with contaminated water for many years. These results appear in JAMA.
Scientists from Columbia University, the Columbia Mailman School of Public Health and New York University led the analysis, which addresses a widespread health concern. Naturally occurring arsenic in groundwater remains a significant challenge across the world. In the United States, more than 100 million people depend on groundwater that can contain arsenic, particularly those using private wells. Arsenic continues to be one of the most common chemical contaminants in drinking water.
“We show what happens when people who are chronically exposed to arsenic are no longer exposed,” said co-lead author Lex van Geen of the Lamont-Doherty Earth Observatory, part of the Columbia Climate School. “You’re not just preventing deaths from future exposure, but also from past exposure.”
Two Decades of Data Strengthen the Evidence
Co-lead author Fen Wu of NYU Grossman School of Medicine said the findings offer the clearest proof yet of the connection between lowering arsenic exposure and reduced mortality risk. Over the course of two decades, the researchers closely tracked participants’ health and repeatedly measured arsenic through urine samples, which strengthened the precision of their analysis.
“Seeing that our work helped sharply reduce deaths from cancer and heart disease, I realized the impact reaches far beyond our study to millions in Bangladesh and beyond now drinking water low in arsenic,” said Joseph Graziano, Professor Emeritus at Columbia Mailman School of Public Health and principal investigator of the NIH-funded program. “A 1998 New York Times story first brought us to Bangladesh. More than two decades later, this finding is deeply rewarding. Public health is often the ultimate delayed gratification.”
Clear Drop in Risk When Arsenic Exposure Falls
People whose urinary arsenic levels fell from high to low had mortality rates that matched those who had consistently low exposure for the entire study. The size of the drop in arsenic was closely tied to how much mortality risk declined. Those who continued drinking high-arsenic water did not show any reduction in chronic disease deaths.

Arsenic naturally accumulates in groundwater and has no taste or smell, meaning people can drink contaminated water for years without knowing it. In Bangladesh, an estimated 50 million people have consumed water exceeding the World Health Organization’s guideline of 10 micrograms per liter. The WHO has described this as the largest mass poisoning in history.
From 2000 to 2022, the Health Effects of Arsenic Longitudinal Study (HEALS) monitored thousands of adults in Araihazar, Bangladesh. The project tested more than 10,000 wells in a region where many families rely on shallow tube wells with arsenic levels ranging from extremely low to dangerously high.
Researchers periodically measured arsenic in participants’ urine, a direct marker of internal exposure, and recorded causes of death. These detailed data allowed the team to compare long-term health outcomes for people who reduced their exposure with those who remained highly exposed.
Community Efforts Created a Natural Comparison Group
Throughout the study period, national and local programs labeled wells as safe or unsafe based on arsenic levels. Many households switched to safer wells or installed new ones, while others continued using contaminated water. This created a natural contrast that helped researchers understand the effects of reducing exposure.
Arsenic exposure decreased substantially in Araihazar during the study. The concentration in commonly used wells fell by about 70 percent as many families sought cleaner water sources. Urine tests confirmed a corresponding decline in internal exposure, averaging a 50 percent reduction that persisted through 2022.

Reduced Exposure Brings Lasting Health Benefits
These trends held true even after researchers accounted for differences in age, smoking and socioeconomic factors. Participants who remained highly exposed, or whose exposure rose over time, continued to face significantly higher risks of death from chronic diseases.
The researchers compared the health benefits of lowering arsenic to quitting smoking. The risks do not disappear immediately but drop gradually as exposure decreases.
In Bangladesh, well testing, labeling unsafe sources, drilling private wells and installing deeper government wells have already improved water safety for many communities.
“Our findings can now help persuade policymakers in Bangladesh and other countries to take emergency action in arsenic ‘hot spots’,” said co-author Kazi Matin Ahmed of the University of Dhaka.
To reach more households, the research team is collaborating with the Bangladeshi government to make well data easier to access. They are piloting NOLKUP (“tubewell” in Bangla), a free mobile app created from more than six million well tests. Users can look up individual wells, review arsenic levels and depths, and locate nearby safer options. The tool also helps officials identify communities that need new or deeper wells.
Clean Water Investments Can Save Lives
The study shows that health risks can fall even for people who were exposed to arsenic for years. This highlights an important opportunity: investing in clean water solutions can save lives within a single generation.
“Sustainable funding to support the collection, storage and maintenance of precious samples and data over more than 20 years have made this critically important work possible,” said Ana Navas-Acien, MD, PhD, Professor and Chair of Environmental Health Sciences at Columbia Mailman School of Public Health. “Science is difficult and there were challenges and setbacks along the way, but we were able to maintain the integrity of the samples and the data even when funding was interrupted, which has allowed us to reveal that preventing arsenic exposure can prevent disease.”
The study team included researchers from Columbia University’s Mailman School of Public Health, the New York University Grossman School of Medicine, Lamont-Doherty Earth Observatory, Boston University School of Public Health, the Department of Geology at the University of Dhaka and the Institute for Population and Precision Health at the University of Chicago.
The HEALS project was launched by Columbia University through the National Institute of Environmental Health Sciences’ Superfund Research Program, with most U.S. collaborators based at Columbia when the study began.

Scientists have long recognized that conditions affecting the body can also influence the brain. Issues such as obesity, high blood pressure and insulin resistance place strain on the body’s metabolic and vascular systems. Over time, this buildup of stress can accelerate cognitive decline and raise the likelihood of Alzheimer’s disease.
Researchers at Arizona State University, working with partners at several institutions, now report that these effects may appear much earlier than expected. In young adults with obesity, the team identified biological markers linked to inflammation, liver strain and early injury to brain cells. These small but measurable shifts resemble patterns seen in older adults with cognitive impairment.
The study uncovered another important finding. Many of the young adults showed unusually low blood levels of choline, a nutrient essential for supporting liver health, regulating inflammation and protecting long-term brain function.
“This research adds to the growing evidence that choline is a valuable marker of metabolic and brain dysfunction — and reinforces the importance of sufficient daily intake, as it is essential for human health,” says Ramon Velazquez. “Several new reports published this month further link reduced blood choline levels to behavioral changes, including anxiety and memory impairment, as well as broader metabolic dysfunction.”
Velazquez leads the study as part of the ASU-Banner Neurodegenerative Disease Research Center, working with colleagues from the ASU School of Life Sciences, Banner Sun Health Research Institute and Mayo Clinic, AZ. The findings were published in Aging and Disease.
Obesity’s Early Impact on Brain Biology
Although obesity is widely known to increase the risk of chronic conditions such as heart disease and type 2 diabetes, this study suggests its influence on the brain may develop much earlier. The researchers measured elevated levels of inflammation-promoting proteins and enzymes that indicate liver stress. They also detected higher levels of neurofilament light chain (NfL), a protein released when neurons are damaged. NfL was linked to low blood choline levels in these young adults, even though no behavioral changes would typically be expected at this age.

NfL has emerged as an important early signal of neurodegeneration. It is found at elevated levels in people with mild cognitive impairment and Alzheimer’s disease. Observing these markers in young adults is significant and suggests that obesity may create measurable effects in the brain well before symptoms appear.
The results support the idea that inflammation, metabolic strain and early neuronal changes may be connected in a way that starts much earlier in life than once believed.
Choline’s Influence on Brain and Metabolic Health
A central aspect of the study involves choline, a nutrient essential for cell-membrane structure, inflammation control, liver function and the production of acetylcholine, a neurotransmitter important for memory. Participants with obesity had substantially lower levels of circulating choline, and these reductions corresponded with stronger signs of inflammation, insulin resistance, liver-enzyme elevation and NfL.
Although the liver produces some choline, most must come from food. Rich dietary sources include eggs, poultry, fish, beans and cruciferous vegetables such as broccoli, cauliflower and brussels sprouts. The researchers also observed that women in the study had lower choline levels than men, a notable finding because women experience higher rates of cognitive aging and Alzheimer’s disease.
National nutrition surveys show that many Americans do not meet recommended choline intake, especially teenagers and young adults. Since choline supports the brain and liver, long-term shortages may heighten vulnerability to metabolic stress and intensify the effect obesity has on the brain.

“Most people don’t realize they aren’t getting enough choline,” said Wendy Winslow, first co-author. “Adding choline-rich foods to your routine can help reduce inflammation and support both your body and brain as you age.”
Nutrient Considerations for New Weight-Loss Drugs
Modern weight-loss drugs have transformed obesity treatment because of their effectiveness in reducing weight and improving metabolic and cardiovascular health. However, the appetite-suppressing effects of GLP-1 medications significantly reduce food intake. This may lead to inadequate consumption of choline and other key nutrients. The authors note the need for future studies to explore whether pairing GLP-1 therapies with adequate dietary choline can help maintain metabolic resilience and overall health.
Study Design and Key Measurements
The research involved 30 adults in their 20s and 30s, split evenly between those with obesity and those of healthy weight. Each participant provided a fasting blood sample. The samples were analyzed for circulating choline, inflammatory cytokines, insulin, glucose, liver enzymes, additional metabolic measures and NfL.
Comparisons between groups revealed consistent patterns: lower choline levels, greater inflammation, metabolic stress and signs of neuronal damage in young adults with obesity. To understand how these findings relate to brain aging, the team compared their results with data from older adults diagnosed with mild cognitive impairment or Alzheimer’s disease.
The same pairing of low choline and high NfL was found in both young and older adults. This suggests that biological changes associated with Alzheimer’s may begin many years before symptoms arise, especially in people experiencing metabolic stress or obesity.
Early Indicators of Long-Term Cognitive Risk
Overall, the study highlights a strong link among obesity, inflammation, choline status and early neuronal stress. This combination may help explain why metabolic disorders increase the likelihood of cognitive decline later in life.
Although the study does not establish causation, it reveals a group of biomarkers that closely resemble those found in older adults with cognitive impairment. The results also align with earlier rodent studies showing that inadequate choline intake in mice can lead to obesity, metabolic problems and increased Alzheimer’s disease pathogenesis.
“Our results suggest that, in young adults, good metabolic health and adequate choline contribute to neuronal health, laying the groundwork for healthy aging,” says Jessica Judd, co-author of the study.
Ongoing research will continue exploring how early metabolic stress may shape long-term risk for neurodegenerative disease and could eventually inform new strategies to protect brain health across the lifespan.

New findings indicate that people who do not treat obstructive sleep apnea face a greater likelihood of developing Parkinson’s disease. Using continuous positive airway pressure, or CPAP, can help lower that risk by improving sleep quality and maintaining steady airflow throughout the night.
The study was published on November 24 in JAMA Neurology and analyzed electronic health records from more than 11 million U.S. military veterans who received care through the Department of Veterans Affairs between 1999 and 2022.
Researchers from Oregon Health & Science University and the Portland VA Health Care System led the project.
Parkinson’s Risk Increases With Age
Parkinson’s is a progressive neurological disorder that affects an estimated 1 million people in the United States. The chance of developing the disease grows gradually each year after age 60.
The new research suggests that long-term, untreated sleep apnea may contribute to a higher risk of Parkinson’s.
Strong Association After Adjusting for Key Factors
Even after accounting for important contributors such as obesity, age and high blood pressure, the investigators still found a clear association between untreated sleep apnea and Parkinson’s disease. Among the millions of veterans with sleep apnea, those who did not use CPAP were nearly twice as likely to be diagnosed with Parkinson’s compared with individuals who used the therapy.

“It’s not at all a guarantee that you’re going to get Parkinson’s, but it significantly increases the chances,” said co-author Gregory Scott, M.D., Ph.D., assistant professor of pathology in the OHSU School of Medicine and a pathologist for at the VA Portland.
How Sleep Apnea Affects the Brain
Sleep apnea occurs when a person’s breathing repeatedly stops and restarts during sleep, which can keep the body from getting sufficient oxygen.
“If you stop breathing and oxygen is not at a normal level, your neurons are probably not functioning at a normal level either,” said lead author Lee Neilson, M.D., assistant professor of neurology at OHSU and a staff neurologist at the Portland VA. “Add that up night after night, year after year, and it may explain why fixing the problem by using CPAP may build in some resilience against neurodegenerative conditions, including Parkinson’s.”
Potential to Change Clinical Practice
Neilson said the results reinforce the importance of prioritizing sleep health for his patients, particularly in light of the elevated Parkinson’s risk revealed in the study.

“I think it will change my practice,” he said.
Veterans Report Clear Benefits From CPAP
Scott noted that some people with sleep apnea are hesitant to use CPAP, but he emphasized that many veterans have strongly positive experiences with the device.
“The veterans who use their CPAP love it,” he said. “They’re telling other people about it. They feel better, they’re less tired. Perhaps if others know about this reduction in risk of Parkinson’s disease, it will further convince peopel with sleep apnea to give CPAP a try.”
Study Contributors and Funding Support
In addition to Scott and Neilson, co-authors include Isabella Montano, B.A., Jasmin May, M.D., Ph.D., Jonathan Elliott, Ph.D., and Miranda Lim, M.D., Ph.D., of OHSU and the Portland VA Health Care System; and Yeilim Cho, M.D., and Jeffrey Iliff, Ph.D., of the University of Washington and the VA Puget Sound Health Care System.
The research received support from the VA through grant awards BX005760, CX00253, I01RX004822, I01RX005371, CX002022, BX006155 and Bx006155; the John and Tami Marick Family Foundation; the Collins Medical Trust; the National Institute on Aging of the National Institutes of Health, award P30AG066518; and the U.S. Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick, Maryland 21702-5014, under award numbers HT9425-24-1-0774 and HT9425-24-1-0775. The authors note that the opinions, interpretations, conclusions and recommendations are their own and are not necessarily endorsed by the Department of Defense, the NIH, VA or other funders.

An NHS resident doctor has been suspended by a medical tribunal for 15 months after posting alleged antisemitic comments on social media.Dr Rahmeh Aladwan, a 31-year-old trainee trauma and orthopaedic surgeon, was also alleged to have expressed support for “violent action and terrorist organisations”.The Medical Practitioners Tribunal Service (MPTS) said Dr Aladwan’s posts “may impact on patient confidence” in both her and the profession, while patients could be “discouraged” from seeking treatment from her.Dr Aladwan denies making racist or hate speech.She is currently the subject of a fitness to practise investigation by the General Medical Council (GMC), an independent body that regulates doctors, physician associates and anaesthesia associates to protect patient safety.The GMC began its investigation following complaints that Dr Aladwan had made antisemitic or offensive comments on posts that also appeared to support terrorism.The tribunal heard that Dr Aladwan’s alleged posts on X included antisemitic conspiracy theories as well as posts that “demonise, or express and encourage hatred towards Jews in general, their history and their way of life”.Her lawyer told the tribunal there was “no evidence” that her activities have had “any impact on patient safety or her ability to fulfil her duties as a doctor”.Dr Aladwan’s suspension will take effect from today and will be reviewed within six months.The hearing, which took place in Manchester, was an interim orders tribunal (IOT), deciding whether Dr Aladwan’s practice should be restricted while the GMC’s investigation takes place.It does not rule on the allegations under investigation.In the tribunal’s ruling, it said it “notes that there is no information to suggest that any patient complaints have been raised or that any patients have come to harm”.Dr Aladwan was previously subject to an IOT in September, which determined that no restrictions should be imposed upon her.On 3 October 2025, a decision was made to refer Dr Aladwan’s case to an IOT hearing again after the GMC alleged an “escalation in the tone of Dr Aladwan’s social media posts” following the September ruling and the Manchester synagogue attack in early October.Responding to the tribunal’s ruling on X, Dr Aladwan said: “Let this decision stand as the definitive proof that there is no independent British medical regulation. The ‘Israeli’ and Jewish lobby decide who can and cannot practise medicine in Britain.”She added: “This is not an end. It is the beginning of a far greater battle for the integrity of our institutions.”The GMC’s social media guidance states that medical professionals have the right to “freedom of belief, privacy, and expression” but that using social media as a medical professional “has to be balanced with the possible impact on other people’s rights and interests”.

14 hours agoShareSaveJuliette Parkin

Scientists have found that rheumatoid arthritis (RA) begins long before the first aches or stiffness appear. Instead of starting when joint pain becomes noticeable, the disease quietly builds over many years. RA is a chronic autoimmune disorder that leads to inflammation and damage in the joints.
According to new research, people who are at higher risk for RA undergo major changes in their immune system well before symptoms surface. Their bodies are already engaged in an unseen autoimmune struggle during this early, silent period.
A Multi-Institution Study Maps RA’s Hidden Early Phase
Researchers from the Allen Institute, CU Anschutz, University of California San Diego, and the Benaroya Research Institute worked together to uncover these early immune changes. Their findings, published in Science Translational Medicine, offer the most detailed view to date of how RA takes shape. By charting immune activity in individuals at risk, the team showed that the disease process is already underway long before joint problems are noticeable. These insights may help guide earlier intervention and possibly prevent disease onset.
“Overall, we hope this study raises awareness that rheumatoid arthritis begins much earlier than previously thought and that it enables researchers to make data-driven decisions on strategies to disrupt disease development,” said Mark Gillespie, Ph.D., assistant investigator at the Allen Institute and co-senior author with Kevin Deane (CU Anschutz), M.D./Ph.D.; Adam Savage (Allen Institute), Ph.D.; Troy Torgerson (Allen Institute), M.D./Ph.D.; and Gary S. Firestein (UC San Diego), M.D. The research followed individuals with ACPA antibodies over seven years. These antibodies are well-established biomarkers for those at risk for RA. During the study, the team uncovered previously unrecognized contributors to disease progression, including widespread inflammation, immune system malfunction, and shifts in how certain immune cells function.
“We expect that going forward the findings from this study will support additional studies to identify ways to better predict who will get RA, identify potential biologic targets for preventing RA as well as identify ways to improve treatments for those with existing RA,” said Kevin Deane, M.D./Ph.D.
Key Findings Widespread inflammation: The researchers observed that people at risk for RA already showed signs of systemic inflammation throughout the body. This inflammation was not limited to the joints. Instead, it resembled the body-wide inflammatory pattern commonly seen in individuals with active RA. Immune cell dysfunction: Multiple immune cell types showed unusual behavior. B cells, which normally create protective antibodies, were found in a heightened pro-inflammatory state. T helper cells, especially those similar to Tfh17 cells, had expanded far beyond typical levels. These cells help coordinate immune responses, including the creation of autoantibodies (antibodies that attack the body’s own tissues). Their expansion helps explain why the immune system begins targeting healthy tissue. Cellular reprogramming: One of the most striking discoveries was that even “naive” T cells, which have not yet encountered pathogens, showed epigenetic changes. Although their DNA sequence remained intact, the regulation of their genes had shifted. This altered gene activity suggests these cells were being reprogrammed before encountering any threats. Joint-like inflammation detected in blood: The team also found that monocytes (a type of white blood cell) circulating in the bloodstream were producing high amounts of inflammatory molecules. Remarkably, these cells closely resembled the macrophages typically found in the inflamed joints of RA patients, indicating that the immune system was already setting the stage for joint inflammation.Toward Early Detection and Preventive Treatment
The findings highlight new early-warning indicators (biomarkers and immune signatures) that could help doctors determine which at-risk individuals are most likely to develop RA. Identifying the disease during this hidden phase may make it possible to monitor patients more closely and begin treatment earlier. If this process is caught in time, RA may be prevented before joint damage begins — potentially sparing patients years of pain and disability. The research supports a shift from reacting to joint damage after it appears to preventing RA at its earliest stages.

Stanford Medicine scientists report that giving mice both blood-forming stem cells and pancreatic islet cells from an immunologically mismatched donor either completely prevented or fully reversed Type 1 diabetes. In this disease, the body’s own immune defenses mistakenly attack and destroy the insulin-producing islet cells in the pancreas.
None of the animals developed graft-versus-host disease, a condition in which the immune system arising from the donated blood stem cells attacks healthy tissue in the recipient, and the destruction of islet cells by the animals’ original immune system came to a stop. After receiving the transplants, the mice no longer needed immune suppressive drugs or insulin at any point during the six-month study.
“The possibility of translating these findings into humans is very exciting,” said Seung K. Kim, MD, PhD, the KM Mulberry Professor and a professor of developmental biology, gerontology, endocrinology and metabolism. “The key steps in our study — which result in animals with a hybrid immune system containing cells from both the donor and the recipient — are already being used in the clinic for other conditions. We believe this approach will be transformative for people with Type 1 diabetes or other autoimmune diseases, as well as for those who need solid organ transplants.”
Kim, who directs the Stanford Diabetes Research Center and the Northern California Breakthrough T1D Center of Excellence, is the senior author of the study, which published online Nov. 18 in the Journal of Clinical Investigation. Graduate and medical student Preksha Bhagchandani is the lead author of the research.
Building on earlier stem cell and islet work
The new results extend a 2022 study by Kim and his collaborators. In that earlier work, the researchers first triggered diabetes in mice by using toxins to destroy the insulin-producing cells in the pancreas. They then used a gentle pre-transplant preparation involving immune-targeting antibodies and low-dose radiation, followed by a transplant of blood stem cells and islet cells from an unrelated donor, to restore blood sugar control.
In the latest study, the team set out to solve a more difficult challenge: preventing or curing diabetes driven by autoimmunity, where the immune system spontaneously targets and kills the body’s own islet cells. In people, this form of the disease is known as Type 1 diabetes. Unlike the induced-diabetes model, where the main goal was to stop the recipient’s immune system from rejecting donor islet cells, the new model involved transplanted islets that faced two problems at once. They were recognized as foreign tissue and were also targeted by an immune system already primed to attack islet cells from any source.

“Just like in human Type 1 diabetes, the diabetes that occurs in these mice results from an immune system that spontaneously attacks the insulin-producing beta cells in pancreatic islets,” Kim said. “We need to not only replace the islets that have been lost but also reset the recipient’s immune system to prevent ongoing islet cell destruction. Creating a hybrid immune system accomplishes both goals.”
Unfortunately, the same biological traits that cause autoimmune diabetes in these mice also make them harder to prepare safely for a blood stem cell transplant.
Simple drug tweak enables full diabetes protection
The team found a relatively straightforward way around this problem. Bhagchandani and Stephan Ramos, PhD, a postdoctoral fellow and co-author of the study, added a medication commonly used to treat autoimmune diseases to the pre-transplant regimen that had been identified in 2022. With this adjusted protocol, followed by blood stem cell transplantation, the mice developed a hybrid immune system made up of cells from both donor and recipient and did not go on to develop Type 1 diabetes in 19 out of 19 cases. In a separate group of animals with long-standing Type 1 diabetes, nine out of nine were cured after receiving the combined blood stem cell and islet cell transplant.
Because the antibodies, drugs and low-dose radiation used in the mice are already part of standard clinical practice for blood stem cell transplantation, the researchers see moving this strategy toward trials in people with Type 1 diabetes as a realistic next step.
From kidney tolerance to hybrid immunity for diabetes
This new work builds on research led by the late Samuel Strober, MD, PhD, a professor of immunology and rheumatology, and his colleagues, including study co-author and professor of medicine Judith Shizuru, MD, PhD. Strober, Shizuru and other Stanford investigators had shown that a bone marrow transplant from a partially immunologically matched human donor could create a hybrid immune system in the recipient and allow long-term acceptance of a kidney transplant from the same donor. In some patients, they found that kidney function from the transplanted organ remained stable for decades without the need for ongoing drugs to prevent rejection.

Blood stem cell transplants are already used to treat cancers of the blood and immune system, including leukemia and lymphoma. However, in cancer care these procedures typically require high doses of chemotherapy and radiation to eliminate the original blood and immune system, which often causes serious side effects. Shizuru and colleagues have designed a safer, less intense way to prepare people with non-cancerous conditions such as Type 1 diabetes for donor blood stem cell transplantation, reducing bone marrow activity just enough to let donor blood stem cells settle in and grow.
“Based on many years of basic research by us and others, we know that blood stem cell transplants could also be beneficial for a wide range of autoimmune diseases,” Shizuru said. “The challenge has been to devise a more benign pre-treatment process, diminishing risk to the point that patients suffering from an autoimmune deficiency that may not be immediately life-threatening would feel comfortable undergoing the treatment.”
“Now we know that the donated blood stem cells re-educate the recipient animal’s immune system to not only accept the donated islets, but also not attack its healthy tissues, including islets,” Kim said. “In turn, the donated blood stem cells and the immune system they produce learn to not attack the recipient’s tissues, and graft-versus-host disease can be avoided.”
Future hurdles for Type 1 diabetes treatment
Although the mouse results are encouraging, significant obstacles remain before this strategy could be widely used to treat Type 1 diabetes. Pancreatic islets can currently be obtained only from deceased donors, and the blood stem cells need to come from the same individual as the islets. It is also uncertain whether the number of islet cells typically recovered from a single donor would always be sufficient to reverse established Type 1 diabetes.
The scientists are exploring ways to overcome these limitations. Possible solutions include producing large amounts of islet cells in the laboratory from pluripotent human stem cells or developing methods that help transplanted donor islets survive longer and function more efficiently after transplantation.
Beyond diabetes, Kim, Shizuru and their collaborators believe that the gentle pre-conditioning strategy they have developed could open the door to stem cell transplants for other autoimmune diseases such as rheumatoid arthritis and lupus and for non-cancerous blood disorders like sickle cell anemia (for which current blood stem cell transplant methods remain harsh), as well as for transplants involving mismatched solid organs.
“The ability to reset the immune system safely to permit durable organ replacement could rapidly lead to great medical advances,” Kim said.
The study was funded by the National Institutes of Health (grants T32 GM736543, R01 DK107507, R01 DK108817, U01 DK123743, P30 DK116074 and LAUNCH 1TL1DK139565-0), the Breakthrough T1D Northern California Center of Excellence, Stanford Bio-X, the Reid Family, the H.L. Snyder Foundation and Elser Trust, the VPUE Research Fellowship at Stanford, and the Stanford Diabetes Research Center.