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The study was published in Nature Communications. It revealed a tiny genetic difference in an immune protein called Fas Ligand (FasL) between humans and non-human primates. This genetic mutation makes the FasL protein vulnerable to being disabled by plasmin, a tumor-associated enzyme. This vulnerability seems unique to humans and is not found in non-human primates, such as chimpanzees.

“The evolutionary mutation in FasL may have contributed to the larger brain size in humans,” said Jogender Tushir-Singh, senior author for the study and an associate professor in the Department of Medical Microbiology and Immunology. “But in the context of cancer, it was an unfavorable tradeoff because the mutation gives certain tumors a way to disarm parts of our immune system.”

Tumor environment neutralizes key immune protein

FasL is an immune cell membrane protein that triggers a programmed cell death called apoptosis. Activated immune cells, including CAR-T cells made from a patient’s immune system, use apoptosis to kill cancer cells.

The UC Davis team discovered that in human genes, a single evolutionary amino acid change — serine instead of proline at position 153 — makes FasL more susceptible to being cut and inactivated by plasmin.

Plasmin is a protease enzyme that is often elevated in aggressive solid tumors like triple negative breast cancer, colon cancer and ovarian cancer.

This means that even when human immune cells are activated and ready to attack the tumor cells, one of their key death weapons — FasL — can be neutralized by the tumor environment, reducing the effectiveness of immunotherapies.

The findings may help explain why CAR-T and T-cell-based therapies can be effective in blood cancers but often fall short in solid tumors. Blood cancers often do not rely on plasmin to metastasize, whereas tumors like ovarian cancer rely heavily on plasmin to spread the cancer.

Plasmin inhibitors may enhance immunotherapy

Significantly, the study also showed that blocking plasmin or shielding FasL from cleavage can restore its cancer-killing power. That finding may open new doors for improving cancer immunotherapy.

By combining current treatments with plasmin inhibitors or specially designed antibodies that protect FasL, scientists may be able to boost immune responses in patients with solid tumors.

“Humans have a significantly higher rate of cancer than chimpanzees and other primates. There is a lot that we do not know and can still learn from primates and apply to improve human cancer immunotherapies,” said Tushir-Singh. “Regardless, this is a major step toward personalizing and enhancing immunotherapy for the plasmin-positive cancers that have been difficult to treat.”

A new groundbreaking study by researchers from University of Birmingham, UCL, Great Ormond Street Hospital and Birmingham Children’s Hospital has revealed important clues into what is driving disease in children with arthritis.

Cutting-edge techniques have allowed scientists for the first time to uncover the unique architecture of cells and signals inside the joint as inflammation takes hold.

The new study published in Science Translational Medicine looks at arthritis in children, caused by the immune system mistakenly attacking joints. Juvenile idiopathic arthritis affects more than 10,000 children in the UK. It causes swelling, stiffness and pain in the joints over years or decades, leading to damage of the joints and long-term disability. Whilst treatments are available to manage the condition, and in some cases achieve remission, there is no cure. It can take time to find which treatment works for each person. Treatments don’t work in the same way for every child, suggesting there are hidden differences between individuals that we are only beginning to understand.

Deepening the scientific and clinical community’s understanding of the condition is vital if more effective treatments are to be found, and undertaking biopsies in young children provides a new way forward. Working with families of children with arthritis opened the door to this study, as the families advocated for the potential of the study, agreeing that the procedure would be acceptable to families, especially compared to living with a chronic inflammatory disease.

In a world first, tiny tissue samples were collected from the joint lining when children were having medicine injected into the joint. These samples were then analysed with advanced imaging and gene-profiling technologies. The fine resolution maps of the joints revealed differences between children of different ages and cell changes in those with more severe disease. These unique cellular fingerprints may help researchers understand why some drugs work better for some children, and not others. The joints of children with arthritis looked significantly different to those with adults, demonstrating the need to understand arthritis in children better. 

We know how frustrating it can be for families and young people to find a drug that best works for their arthritis. Finding ways to better predict which medicines will be beneficial for a particular child would mean we were able to treat the disease more rapidly and effectively. To achieve this goal, we first needed to understand what cells make-up the lining of the joint where the inflammation occurs.

Equipped with that knowledge, we can now start to tackle the next challenge, determining how these cellular fingerprints within the joint tissue can help us predict which drug will work best, ensuring we give the right drug, to the right child, at the right stage of their disease.” 

Professor Adam Croft, Versus Arthritis Professor of Rheumatology at the University of Birmingham and chief investigator of the study

One of the children who took part in the study was Aurelia, from London, who was diagnosed with arthritis after injuring her knee while on holiday.

“Aurelia is a sporty child and loves art, drama, music and ballet. We noticed pain and swelling of her knee whilst on holiday. We thought perhaps she had injured it playing, but when this didn’t get better and she was struggling to walk, we realised something else was wrong. She was referred to the Rheumatology team at Great Ormond Street Hospital who diagnosed her with arthritis. This came as a bit of a shock given how active she is!

“They offered her a steroid injection in her knee under general anesthetic to alleviate the symptoms. The team asked if we were happy for her to take part in this research study and collect some tissue samples at the same time.

“We were keen for her to be involved, as there’s still a lot of unknowns with arthritis in children, and not all treatments can work. Given that she was already having an anaesthetic, and it wasn’t an additional operation for her, it was a great opportunity for researchers to take samples and to be better able to study the conditions. We hope the study will help other families with children in similar positions to us,” explained Aurelia’s mum, Emily.

Professor Lucy Wedderburn, University College London Great Ormond Street Institute of Child Health and Consultant of Paediatric Rheumatology at Great Ormond Street Hospital said:

“This study represents a real step change in our work with children and young people who live with arthritis, and has been a huge team effort. Rather than having to rely on blood tests which often do not tell us accurately what is happening in the joint, we can now directly analyse the joint lining, across different types of childhood arthritis and different ages. Our findings show that younger children have different types of immune cells invading their joints compared to older children. Samples from children with arthritis looked different to adult samples, with a different make up of immune cells, blood vessels and distinct connective tissue cells. This suggests that treatments may need to vary depending on age and shows why we can’t just extend studies from adult studies to understand arthritis in children.”

The study was funded by the Medical Research Council, Versus Arthritis, National Institute of Health and Care Research, Great Ormond Street Hospital Charity, amongst others, and delivered through the National Institute for Health and Care Research (NIHR) Birmingham Biomedical Research Centre (BRC).

Lucy Donaldson, Director of Research at Versus Arthritis said:

“People with arthritis should never be reduced to just their condition. Each person deserves to be treated holistically as an individual, including, of course, children and young people with arthritis.

“We are very proud to invest in truly innovative research like the MAPJAG study which is helping us to better understand the individual differences between young people with juvenile arthritis.

“The MAPJAG team’s findings clearly show that children and young people aren’t just small adults, but have a different “cellular fingerprint”. Importantly the team have also shown that this can change with age. The findings can give real hope to all those families that more can be done, sooner, to enable young people with arthritis to live the lives they choose.” 

A wider programme of work, made possible by a Medical Research Council partnership award known as Tissue Research in Childhood Arthritis (TRICIA), supports the infrastructure needed for multi-centre tissue research of the joint. In future, it is hoped that a larger study, involving more centres will allow researchers to dig deeper into the remaining questions about how best to tailor treatments for individual patients.

Instrumental to driving this research forward was Dr Eslam Al-Abadi, a study investigator from the Birmingham Women’s and Children’s Hospital NHS Foundation Trust, who sadly passed away before publication. His incredible efforts in seeking to improve the care of children with this disease are gratefully acknowledged.

Chronic inflammation occurs when the immune system is stuck in attack-mode, sending cell after cell to defend and repair the body for months or even years. Diseases associated with chronic inflammation, like arthritis or cancer or autoimmune disorders, weigh heavily on human health-and experts anticipate their incidence is on the rise. A new study by investigators from Mass General Brigham identified a protein called WSTF that could be targeted to block chronic inflammation. Crucially, this strategy would not interfere with acute inflammation, allowing the immune system to continue responding appropriately to short-term threats, such as viral or bacterial infection. Results are published in Nature.

Chronic inflammatory diseases cause a great deal of suffering and death, but we still have much to learn about what drives chronic inflammation and how to treat it. Our findings help us separate chronic and acute inflammation, as well as identify a new target for stopping chronic inflammation that results from aging and disease.”

Zhixun Dou, PhD, senior author of the Center for Regenerative Medicine and Krantz Family Center for Cancer Research at Massachusetts General Hospital

Using chronically inflamed human cells, the researchers found that WSTF interacts with other proteins inside cell nuclei, which prompts its excretion and degradation. Since WSTF is responsible for concealing pro-inflammatory genes, this nucleus-eviction reveals those genes and, in turn, amplifies inflammation. They confirmed that WSTF loss could promote inflammation in mouse models of aging and cancer. They also found, using human cells, that WSTF loss only occurred in chronic inflammation, not acute. Using these findings, the researchers designed a WSTF-restoring therapeutic to suppress chronic inflammation and observed preliminary success in mouse models of aging, metabolic dysfunction-associated steatohepatitis (MASH), and osteoarthritis.

The researchers went further to examine tissue samples from patients with MASH or osteoarthritis. They found that WSTF is lost in the livers of patients with MASH, but not in the livers of healthy donors. Using cells from the knees of osteoarthritis patients undergoing joint replacement surgery, they showed that WSTF-restoring therapeutic reduces chronic inflammation from the inflamed knee cells. These findings highlight the potential of developing new treatments targeting WSTF to combat chronic inflammatory diseases.

Further research is needed to validate the therapeutic potential of WSTF restoration in broader settings and to develop specific strategies to target WSTF. Additionally, the findings suggest other similar proteins may be involved in chronic inflammation, opening a promising new avenue for studying and treating inflammation in the future.

A study published in Cell Stem Cell reveals that some mutations in blood stem cells might help protect against late-onset Alzheimer’s disease.

A team led by researchers at Baylor College of Medicine discovered that both a mouse model and people carrying blood stem cells with mutations in the gene TET2, but not in the gene DNMT3A, had a lower risk for developing Alzheimer’s disease. Their study proposes a mechanism that can protect against the disease and opens new avenues for potential strategies to control the emergence and progression of this devastating condition.

“Our lab has long been studying blood stem cells, also called hematopoietic stem cells,” said lead author Dr. Katherine King, professor of pediatrics – infectious diseases and a member of the Center for Cell and Gene Therapy and the Dan L Duncan Comprehensive Cancer Center at Baylor. She also is part of Texas Children’s Hospital.

Hematopoietic stem cells live in the bone marrow and generate all the different types of blood cells the body needs to stay alive and healthy – red blood cells, immune cells and platelets. As people get older, blood stem cells can develop mutations, and this occurs in about 20% of 70-year-olds. Most of the time, these mutations don’t cause problems, but sometimes, a mutation drives the cells to divide more than others, forming a clone. This process is called clonal hematopoiesis and it has been linked to a higher risk for conditions such as cardiovascular disease, stroke, blood cancers like leukemia and chronic obstructive pulmonary disease. However, many questions remain regarding the connection between clonal hematopoiesis and Alzheimer’s disease.

“In the current study, we investigated the effect of the two genes most commonly mutated in clonal hematopoiesis, TET2 and DNMT3A, on Alzheimer’s disease,” said first author Dr. Katie A. Matatall, instructor in the King lab. “We also selected these mutations because they are involved in inflammation, which is known to be increased in Alzheimer’s disease.”

The researchers assessed the effect of clonal hematopoiesis on the prevalence of Alzheimer’s disease using human data stored in the UK Biobank. They also evaluated the role of mutations in genes Tet2 and Dnmt3a in a mouse model of Alzheimer’s disease.

The team discovered that the two mutations do not behave the same way. Clonal hematopoiesis with the TET2-mutant was associated with a 47% reduced risk of late-onset Alzheimer’s disease in humans, whereas other mutations of clonal hematopoiesis did not confer protection. In a mouse model, transplantation of Tet2-mutant bone marrow reduced cognitive decline and beta-amyloid plaque formation, effects not observed with Dnmt3a-mutant cells.

“Furthermore, we found that the protective effect seemed to be mediated by TET2-clonal stem cells circulating in the blood,” Matatall said. “Immune cells derived from these clones were able to migrate into the brain where they cleared beta-amyloid deposits, a hallmark of Alzheimer’s disease, more effectively than cells without the TET2 mutation. We think that it’s both the increased migration into the brain and the enhanced ability to clear Alzheimer’s-associated damage that drives the better outcomes.”

Until now clonal hematopoiesis has primarily been associated with promoting the progression of disease. This is the first time that these two mutations in blood stem cells have been shown to influence disease in different ways. The findings show that some clonal hematopoiesis promote disease while others, like TET2, may provide protection. We need to think about clonal hematopoiesis in a mutation-specific way and assess their risks and benefits.”

Dr. Katherine King, professor of pediatrics – infectious diseases, Baylor College of Medicine

The findings establish a novel experimental platform for understanding the role of clonal hematopoiesis in Alzheimer’s disease and may inform future approaches to mitigate the risks of central nervous system degenerative diseases.

Source:

Baylor College of Medicine

Journal reference:

Matatall, K. A., et al. (2025). TET2-mutant myeloid cells mitigate Alzheimer’s disease progression via CNS infiltration and enhanced phagocytosis in mice. Cell Stem Cell. doi.org/10.1016/j.stem.2025.06.006.

Adults with poor Life’s Essential 8 scores faced significantly higher atrial fibrillation risk, suggesting that heart-healthy habits could be key to preventing this common arrhythmia.

Study: Association of life’s essential 8 score with incidence of atrial fibrillation: The Framingham heart study. Image Credit: Magic mine / Shutterstock

In a recent study published in the American Journal of Preventive Cardiology, researchers in Boston, USA, investigated the relationship between the Life’s Essential 8 (LE8) score and the risk of atrial fibrillation (AF).

AF is the most common arrhythmia, whose prevalence and incidence are increasing worldwide. Thirty years ago, the Framingham Heart Study (FHS) established age, type 2 diabetes, hypertension, valvular heart disease, heart failure, and coronary heart disease as risk factors for AF. Since then, obesity, metabolic syndrome, excess alcohol intake, and obstructive sleep apnea have been identified as modifiable risk factors for AF pathogenesis.

LE8 is based on the Life’s Simple 7 (LS7), which was developed to define and measure cardiovascular health and promote positive health outcomes. LE8 is an update to LS7 that additionally includes a sleep health metric. Recent studies indicate an inverse relation between the LE8 score and health outcomes, such as fatty liver disease, cardiovascular disease (CVD), kidney disease, dementia, and CVD mortality.

About the study

The present study evaluated the associations between the LE8 score and AF risk. The study population included subjects from the FHS Omni 1 and Offspring cohorts. Individuals aged 45 years or older attending one or more index exam cycles were included in the current analyses. Participants were assigned a composite cardiovascular health score at their index exams based on their adherence to eight healthy lifestyle components.

These lifestyle components included diet, smoking habits, sleep duration, body mass index (BMI), fasting blood glucose, physical activity, cholesterol levels, and blood pressure. The LE8 score was the mean of the scores assigned to each component. The study’s outcome was incident AF, ascertained from electrocardiograms. Subjects were followed up from the date of the index exam until the next index exam, incident AF, death, or for 10 years.

Fine-Gray hazard models, which account for competing mortality risks, were used to evaluate the associations between LE8 and AF risk, adjusted for sex and age. In secondary analyses, separate models were developed for each LE8 component. In addition, the team investigated whether age modified the association between incident AF and LE8. The association between the LE8 score and the risk of all-cause mortality was also assessed.

Findings

The study included 3,161 participants aged 65 years, on average, who contributed 4,628 index exam cycles. Most participants were female (57%) and from the Offspring cohort (93%). The average LE8 score was 67.6 at the index exams. The LE8 score was ≥80 (ideal), <50 (poor), and 50–79 (intermediate) for 16%, 7%, and 76% of participants, respectively. Overall, 410 individuals had incident AF, and 424 deaths occurred over the follow-up.

The risk of incident AF was higher for individuals with poor LE8 scores compared to those with ideal scores. The incidence rate of AF per 1,000 person-years of follow-up was 17.2 for participants with poor LE8 scores, 7.9 for those with ideal scores, and 10.3 for those with intermediate scores. Notably, intermediate cardiovascular health showed no significant difference in AF risk compared to ideal health (sHR=0.95). Moreover, higher continuous scores were associated with a reduced risk of AF.

Subjects with poor scores on the BMI, blood pressure, and glucose components had a greater risk of AF than those with ideal scores on the respective components. There was no evidence that age modified the association between incident AF and LE8. Furthermore, participants with poor LE8 scores had an elevated risk of all-cause mortality relative to those with ideal scores. A more favorable score for physical activity, glucose, and smoking was associated with lower mortality risk.

Conclusions

In sum, the study assessed the risk of incident AF in two FHS cohorts using LE8 scores. AF incidence was 10.4 cases per 1,000 person-years, comparable to estimates from other studies. A poor LE8 score was associated with an increased risk of AF compared to an ideal score. Moreover, higher continuous scores were associated with lower risk of AF and all-cause mortality. Poor blood pressure, glucose, and BMI scores were also associated with a higher AF risk.

An intermediate LE8 score was not associated with the risk of AF. The analysis accounted for repeated participant contributions across exam cycles using statistical clustering methods. Notably, the sample predominantly comprised middle-aged and older adults of European descent (the Offspring cohort), which limits generalizability to younger individuals and other ethnic or racial groups. Recall or misclassification bias was also likely, as several LE8 components were assessed using self-reported data. Future analyses should focus on whether specific interventions or behaviors would augment CVD outcomes.

In 2015, Andre Hoelz, the Mary and Charles Ferkel Professor of Chemistry and Biochemistry and a Howard Hughes Medical Institute investigator, learned he had a rare brain tumor that was pressing on his acoustic nerve. The chemist, who normally focuses on solving the structure of protein assemblies in the lab, set out to learn everything he could about the workings of the auditory system.

Eventually he teamed up with his surgeon, Rick Friedman , who is also a research scientist and vice chair at UC San Diego specializing in disorders of the ear. The two have taken on the search for methods of protecting the inner ear against hearing loss. Now Hoelz and Friedman have received a grant to extend their experimental agenda.

The inner ear is a remarkable but somewhat fragile vehicle for carrying sound from the outer ear to the brain. It does this by means of tiny bundles of hair-like cells that respond to incoming sound waves by releasing neurotransmitters that send sonic information to the brain along the acoustic nerve. These inner ear hair cells are crucial to our hearing. Sadly, however, they cannot be regenerated. Once lost, they are gone forever, and the hearing they enabled is gone with them.

“There are some cells in our body that are so specialized that they cannot be replaced,” Hoelz explains. “The cells that make us hear, along with other sensory cells, fall into this category. We have 37 trillion cells in our body, and only 16,000 of those are involved in hearing. When these cells die, our hearing is gone. And when it comes to inner ear hair cells, it’s not a question of whether they will die, it’s a question of when.”

Inner ear hair cells (IHCs) perish for a variety of reasons, including viral infections, exposure to excessive noise, and normal aging processes. One cause of particularly devastating hearing loss is associated with cisplatin chemotherapy, a robust and taxing regimen of cancer treatment used to treat adult-onset cancers (testicular, head and neck, ovarian, cervical, endometrial, and lung, for example) and pediatric cancers (such as neuroblastoma, osteosarcoma, medulloblastoma, retinoblastoma, and Wilms tumor).

“Especially for pediatric patients, you want to kill as many cancer cells as possible. Children have another 80 years ahead of them, we hope. So, treatments for childhood cancers are aggressive,” Hoelz explains. “Unfortunately, cisplatin chemotherapy may cause severe damage to the ear hairs we need in order to hear. A full 70% of patients that are treated with cisplatin will end up with some degree of hearing loss.”

“There exist no ideal solutions to this toxicity,” Friedman adds.

Hearing loss is particularly damaging for children who are still in the early phase of developing speech and communication. About 2,000 children are exposed to cisplatin each year in the United States. The only currently available treatment approved by the Food and Drug Administration to avoid hearing loss in patients being treated with cisplatin has a serious drawback: It inactivates cisplatin, thereby weakening the effectiveness of the chemotherapy. “This drug is basically an antidote for cisplatin,” Hoelz says.

Cisplatin therapy saves lives that would otherwise be lost to cancer. If the choice comes down to losing one’s hearing or dying, there is usually little debate.

Hoelz himself confronted a similar dilemma in 2015 when he experienced severe vertigo and temporary hearing loss. Doctors discovered that a very rare brain tumor was exerting pressure on his acoustic nerve, affecting his balance and hearing. Since Hoelz’s symptoms came and went, he and his doctors chose to regularly monitor the tumor via MRI and periodically test his hearing. During this time, Hoelz began to see Dr. Friedman. “I had a very distinct feeling that eventually I would need to have surgery, and that Rick was the person to do it,” Hoelz remembers. “But Rick told me I was not the best candidate for ear preservation, so I hesitated. I thought, ‘I may not be lucky, but if not, at least I can keep my hearing for a while.’”

As Friedman monitored Hoelz’s tumor, the two men began to talk science. “It was strange,” Hoelz says. “I was debating whether or not to have the surgery, but alongside that, I was fascinated by Rick’s data on protein complexes involved in hearing and I began to think about how the work I did in my lab could shed light on these processes.”

When Hoelz’s symptoms became markedly worse, he opted to have the surgery and lost hearing in his left ear. But at the same time, he began a collaboration with Friedman that has already shown promising results.

For his part, Friedman says, “Meeting and collaborating with Andre is the best thing that has happened in my scientific career.”

Over the last five years, Hoelz, Friedman, and other scientists in the field have identified a gene that makes people more susceptible to hearing loss-whether from noise, cisplatin, or age-and started exploring ways to strengthen the inner ear hair cells to protect hearing.

Hoelz and Friedman first identified a gene, Prkag2, that encodes part of the AMPK (5′ adenosine monophosphate-activated protein kinase) complex. AMPK is an enzyme that works throughout the body, from the liver to the brain to skeletal muscle, to regulate metabolism. IHCs are highly metabolically active. The synapses that connect IHCs to the auditory nerve rely on AMPK to deliver neurotransmitters-in this case, glutamate-when they are stimulated by sound. Without these deliveries from the AMPK complex, the IHCs cannot communicate auditory information to the brain.

Hoelz and Friedman have shown that they can in fact protect IHCs, and the hearing that relies on them, if an AMPK-activating drug is properly delivered prior to cisplatin treatment. With a grant from Curebound , a philanthropic organization based in San Diego that funds cancer research, they are now learning the correct dosage and timing required to protect the hearing of cisplatin-treated cancer patients. Efficacy is being assessed in murine models. Once an optimal therapy is designed, it will be tested in guinea pigs, whose auditory system is more similar to our own, and finally in humans.

“The hope is that it will be comparatively easy to recruit people for a study of these treatments,” Hoelz says. “If you are being treated with cisplatin, you may lose your hearing anyway, so any chance to preserve at least some hearing should be attractive.”

The possibilities for this therapy do not end there. “We hope that in the long run this will be a sort of ear vitamin that could work for everyone. The treatment would make IHCs sturdier and less susceptible to all sorts of damage, not only that from cisplatin. Just as you can put a veneer on teeth to protect them from cavities, you could use this therapy to boost the longevity of IHCs, potentially allowing them to survive for people’s entire lifespans,” Hoelz says.

“While mammals cannot regenerate IHCs, some fish and birds can,” Hoelz explains. “Somehow as we evolved we lost this ability. Scientists are studying what developmental program might make it possible for humans to regenerate IHCs,” he adds. “But in the meantime, it would be wonderful if we could develop a therapy to protect them. Working with Rick has been a thrilling dive into the world of hair cell biology, opening new scientific doors and sparking a deeply personal hope that this research might one day help preserve hearing-including my own.”

Adopting a Mediterranean diet helped older adults shed weight and improve metabolic health, but new research shows it may not be enough to enhance cognitive function, highlighting the need for longer or more intensive interventions.

Study: Long-term outcomes of a Mediterranean diet with or without calorie restriction on cognition and cardiometabolic health: The building research in diet and cognition trial. Image Credit: Liubomyr Tryhubyshyn / Shutterstock

In a recent study published in the journal Preventive Medicine Reports, researchers in Chicago, USA, investigated whether adopting a Mediterranean Diet (Med Diet) lifestyle, with or without calorie-restricted weight loss, improves cognition and cardiometabolic health over a 14-month period.

Background

Could a plate of olive oil-dressed vegetables protect the aging brain as effectively as expensive drugs? Alzheimer’s dementia impacts about 6.9 million Americans older than 65 years, and pharmacologic options offer only modest relief.

Observational data link both a Med Diet pattern and intentional weight reduction to sharper cognition, yet rigorous evidence is scarce for African American adults, who shoulder disproportionate dementia and obesity burdens in the United States (US). Existing randomized trials are often short, enroll predominantly White volunteers, or fail to distinguish between dietary and weight-loss effects.

About the study

The Building Research in Diet and Cognition (BRIDGE) Randomized Controlled Trial (RCT) enrolled 185 community-dwelling adults aged 55-85 years with obesity. Eligibility included Body Mass Index (BMI) 30-50 kg/m2, low Med Diet adherence, Montreal Cognitive Assessment scores ≥19, and 91% identified as African American. Participants were randomized 2:2:1 to the Med Diet with Weight Loss (MedWL), the Med Diet alone (MedA), or the control group. Stratified blocks balanced age, cognition, and cohort; outcome assessors were blinded.

Both intervention groups attended twenty-five weekly classes for eight months, received extra-virgin olive oil and almonds, and learned to cook using the Mediterranean diet. MedWL additionally pursued 5-7% weight loss via a 25% calorie deficit and 150 minutes per week of moderate-to-vigorous physical activity coached by certified trainers.

All participants then completed a six-month low-contact maintenance phase. Cognition, attention, and information processing (AIP), executive function, and learning, memory, and recognition (LMR) were assessed with standard neuropsychological tests. Secondary outcomes encompassed diet quality, body weight, body composition assessed by Dual-energy X-ray Absorptiometry (DXA), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), High-Sensitivity C-Reactive Protein (hs-CRP), Hemoglobin A1c (HbA1c), and six-minute walk distance. Investigators analyzed intention-to-treat change from baseline to 14 months with linear mixed-effects models that adjusted for cohort, age, and baseline cognitive performance.

It is important to note that, for the third cohort, several physical activity and functional outcome measures, including the six-minute walk test, were affected by the COVID-19 pandemic, as data collection for these outcomes had to be conducted virtually or was omitted due to restrictions.

Study results

Among 185 randomized participants, 162 (88%) contributed outcome data at 14 months. The baseline mean age was 66 years, and the mean BMI was 37.1 kg/m²; 86% of the participants were female.

During the eight-month active phase, adherence to the Med Diet rose markedly in both intervention arms, and weight loss occurred primarily in the MedWL group; these trends largely persisted through the maintenance phase.

Over the full 14 months, adherence scores increased by 3.2 points for MedWL and 3.4 points for MedA, compared to 0.2 points for controls (P < 0.05), indicating sustained dietary change.

MedWL participants recorded an average weight reduction of 3.8 kg, compared with a non-significant 1.7 kg in MedA and 0.5 kg in controls; the difference between MedWL and both comparators was statistically significant.

Visceral adipose tissue mass declined by 151 g in MedWL, representing a significant reduction compared to the control group, but not in the other groups. Additionally, BMI fell by 1.4 kg/m² in MedWL only.

Despite these favorable metabolic shifts, cognitive composites changed similarly across groups.

AIP, Executive Function, and LMR scores each improved modestly within all arms, likely reflecting practice effects; however, no between-group differences emerged from baseline to 14 months or from 8 to 14 months.

Significant between-group differences were also seen in secondary outcomes, including Med Diet adherence, weight, BMI, and visceral adipose tissue mass.

For hs-CRP, the only statistically significant between-group difference was a larger drop in the MedWL group compared to MedA. Changes in other cardiometabolic outcomes such as HOMA-IR, HbA1c, fasting lipids, blood pressure, and six-minute walk distance were modest and did not differ significantly between groups.

Sensitivity analyses excluding measures collected virtually during the Coronavirus Disease 2019 pandemic or omitting tests unavailable to the third cohort yielded similar findings, supporting the accuracy of null cognitive results.

Notably, adherence to the Med Diet waned slightly during maintenance, dropping 2.9 points in MedWL and 1.4 points in MedA; yet, it remained higher than baseline, and weight regain in MedWL was limited to approximately 0.9 kg.

Physical activity, as measured by the Godin questionnaire, increased during classes but remained essentially unchanged from baseline at the end of maintenance in MedWL (change of +0.2). The six-minute walk distance declined in some groups, although for the third cohort, this outcome was omitted due to pandemic-related restrictions.

Systolic and diastolic blood pressure remained unchanged. Insulin and triglyceride values showed wide confidence intervals and no group differences. The paper does not report on adverse events attributable to diet or exercise. These activity trends did not measurably mediate cognitive change.

Conclusions

To summarize, an eight-month Med Diet lifestyle intervention, delivered with or without calorie-restricted weight loss and followed by six months of low-contact maintenance, did not enhance cognition in older African American adults with obesity compared with a usual diet. Nevertheless, participants safely improved dietary quality, and the weight-loss arm achieved clinically meaningful reductions in body weight and visceral adiposity.

These gains underscore the practicality of culturally sensitive group programs for cardiometabolic risk management but suggest that stronger or longer exposures may be required to translate metabolic benefits into cognitive protection. Replication in larger, multi-ethnic cohorts and extended follow-up is warranted. Further research is needed to clarify long-term cognitive influence in diverse communities.

You may have heard that eating before bed is a no-no if weight loss is a goal. However, that couldn’t be further from the truth. And, there’s science to prove it.

A small snack can benefit cardiovascular and metabolic health, as well as promote muscle protein synthesis. You don’t have to avoid snacking at night. And that advice stands if you’re aiming to lose weight. It’s the quality of your snack that matters.

So when you’re looking for a late-night bite, read on. We talked to registered dietitians about what late night snack they’d choose to support weight loss.

The Best Late-Night Snack for Weight Loss

Dig into this creamy Cottage Cheese Snack Jar with Fruit when hunger strikes at night.

If you haven’t embraced the cottage cheese craze, here’s your opportunity. The best late-night snack for weight loss that dietitians swear by is the trendy staple that has social media buzzing. This recipe for a cottage cheese snack jar adds diced peaches and chopped pecans for a sweet and crunchy snack.

“Cottage cheese and fruit is an amazing and delicious late-night snack,” says Lauren Harris-Pincus, M.S., RDN, founder of Nutrition Starring You and author of The Everything Easy Pre-Diabetes Cookbook. “The slow-digesting protein, fiber from the fruit and unsaturated fats from a sprinkle of nuts is a fabulous combo to help balance blood sugar, feed your muscles while you sleep and provide an antioxidant boost,” she explains.

Here’s more about why this snack staple is such a superhero before bed.  

It Contains Sleep-Promoting Tryptophan

Just like turkey on Thanksgiving, dairy foods are a great way to up your intake of tryptophan, says registered dietitian and certified personal trainer Nicole Rodriguez, RDN. Tryptophan is a naturally occurring amino acid that plays an important role in the production of serotonin and sleep-regulating melatonin for sleep. Thanks to this and other amino acids found in dairy, foods like cottage cheese may help support sleep quality.

It’s High in Protein 

Dairy is a powerhouse when it comes to high-quality protein, meaning it contains a complete package of essential amino acids. A ½-cup serving of 1% fat cottage cheese provides 14 grams of protein for just 80 calories and 1 gram of total fat. In fact, research shows that pre-sleep protein, specifically casein, can help your body build muscle when you are engaged in a strength training program. This supports earlier research that suggested that higher-protein diets may also help with appetite and weight management. Choosing a low-fat dairy food like cottage cheese is a great way to add a solid source of protein into your nighttime routine.

It’s Packed with Vitamins and Minerals

Cottage cheese contains calcium, magnesium, zinc and B vitamins. Magnesium and zinc, in particular, play an important supporting role in helping convert tryptophan in dairy foods into melatonin (that circadian rhythm-regulating good sleep hormone).

One caveat when it comes to cottage cheese is its sodium content. Traditional cottage cheese is rather high in sodium, with a ½-cup serving clocking in at 459 milligrams, 20% of the recommended daily limit. If you are trying to reduce the sodium in your diet, choose a no-salt-added cottage cheese or compare the sodium content between brands and pick a lower-salt product.

It Has Fiber

While cottage cheese on its own lacks fiber, the addition of fruits and nuts gives it a nice fiber boost. This recipe supplies 3 grams of fiber. Plus, when some of that fiber comes from fruit, you’re in luck. “The addition of fruit can satisfy sweet cravings that you may be trying to minimize while pursuing a weight-loss goal,” says Rodriguez.

It Has Fat 

Healthy fat sources contribute to snack satiety and satisfaction, says Rodriguez. The Cottage Cheese Snack Jar with Fruit has 2 tablespoons of chopped pecans, though you can change up the nuts if you’d like. Other ideas include slivered almonds, walnut pieces or chopped pistachios.

What to Consider When Choosing a Late-Night Snack

Late-night snacks do not have to involve heading to the pantry to grab potato chips or cookies. (Classic TV munchies, of course.) Those snacks taste good, but there are better choices that align with weight loss. “While I encourage my patients to embrace an ‘all foods fit’ philosophy, nighttime presents its own challenges,” says Rodriguez. For example, eating spicy, fatty or fried foods can cause indigestion, while foods with a lot of added sugars can cause blood glucose spikes. Both of these can disrupt your sleep, and lack of sleep can affect your appetite and may make weight loss more difficult.

But there are two nutrients you should focus on when it comes to nighttime nibbles: protein and fiber, says Harris-Pincus. These provide staying power, she says. “Sticking with these options will help to keep blood sugar levels more stable and offer an opportunity to maximize your nutrient intake for the day.”

• Here are the nutrition parameters to focus on when finding a late-night snack:
• Calories: Aim for roughly 200 calories per snack, depending on your personal energy needs, to avoid feeling overly full before bed. 
• Protein: Make sure your snack choice has protein. Aiming for 7 or more grams provides a good source of protein. 
• Fiber: Fiber helps keep you fuller for longer, and can also support your weight-loss goals through offering satiety, meaning you’re less likely to mindlessly munch. Aim for a snack that provides some fiber, ideally 3 or more grams. 
• Fat: Fat is your friend; it also helps to satiate you. Choose a snack that packs a little bit of unsaturated fat to help provide that staying power until your morning meal. 

Our Expert Take

You can enjoy a late-night snack, even if weight loss is on your radar. Consider your individual calorie, protein and nutrient needs as you explore what foods will satisfy you as well. Dietitians recommend pairing low-fat cottage cheese with fruit and nuts for a late-night option that provides protein, fat and fiber, all nutrients that support weight-loss goals.