As space travel becomes more frequent, a new biomarker tool was developed by an international team of researchers to help improve the growing field of aerospace medicine and the health of astronauts.
Dr. Guy Trudel (Professor in the Faculty of Medicine), Odette Laneuville (Associate Professor, Faculty of Science, and Director of the Biomedical Sciences) and Dr. Martin Pelchat (Associate Professor in the Department of Biochemistry, Microbiology and Immunology) are among the contributors to an international study led by Eliah Overbey of Weill Cornell Medicine and the University of Austin. Published today in Nature it introduces the Space Omics and Medical Atlas (SOMA), a database of integrated data and sample repository from a diverse range of space missions, including from SpaceX and NASA.
Space travel creates cellular, molecular, and physiological shifts in astronauts. SOMA is expected to provide a much necessary biomedical profiling that can help tease out the short and long-term health impacts of spaceflight. This will bring needed health monitoring, risk mitigation, and countermeasures baseline data for upcoming lunar, Mars, and exploration-class missions. It is meant to help keep astronauts and space travelers alive and healthy.
It may also have some intended use here on Earth.
“This represents a breakthrough in the study of human adaptation and life in space. Since many of the changes in astronaut in space resemble those of people who are immobile in bed, these studies can be clinically relevant. The data are therefore important for future space exploration while also providing a correlation to people on Earth with limited mobility or who are bedridden before their rehabilitation,” says Dr. Trudel, a rehabilitation physician and researcher at The Ottawa Hospital who has focused on space travel and its effects on the human immune system.
Highlights of the study, include: The Atlas includes extensive molecular and physiological profiles encompassing genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiome data sets, which reveal some consistent features across missions. Samples were taken pre-flight, during, post-flight and throughout the recovery period. Comprehensive profile of the physiological changes of the I4 crew (ages 29, 38, 42, 51) and 13 unique biospecimen sample types were collected and processed. 2,911 samples were banked with over 1,000 samples processed for sequencing, imaging, and biochemical analysis creating the first-ever aerospace medicine biobank. The SOMA resource represents an over 10-fold increase in total publicly available human space omics data.”The University of Ottawa’s Faculty of Medicine, its Faculty of Science, and The Ottawa Hospital’s Bone and Joint Research laboratory have a long history of contributions and successes in studying human adaptation to space. They also involve students from different programs, providing a unique learning experience in both bone and joint health, and in the rapidly developing field of aerospace medicine,” adds Dr. Trudel.

Sepsis — the leading cause of mortality in children around the world — can present with a wide range of signs and symptoms, making a one-size-fits-all treatment strategy ineffective. Pursuing a precision medicine approach for pediatric sepsis, researchers used artificial intelligence to analyze a large set of clinical data and find a distinct group of patients who might respond better to targeted treatments.
These children share clinical characteristics described as PHES, or persistent hypoxemia (abnormally low oxygen levels in the blood), encephalopathy (brain function disturbance) and shock, which is a highly lethal pattern within sepsis presentations. A recent study validated this pattern and discovered that PHES overlaps with biomarkers that indicate excessive levels of inflammation and endothelial activity (which works in tandem with an overactive immune response). Findings were published in the journal Pediatric Critical Care Medicine.
“The association we found between PHES and a set of biomarkers suggests that this group of children with sepsis could benefit from targeted treatment, such as corticosteroids, for example,” said senior author L. Nelson Sanchez-Pinto, MD, critical care physician as well as Warren and Eloise Batts Research Scholar at Ann & Robert H. Lurie Children’s Hospital of Chicago, and Associate Professor of Pediatrics and Preventive Medicine at Northwestern University Feinberg School of Medicine. “In sepsis care, physicians need to make quick treatment decisions and our study shows that they can base these decisions on a specific pattern within routinely collected clinical data. We are much closer now to precision medicine for sepsis.”
Dr. Sanchez-Pinto explains that clinical trials are still needed to test various targeted treatments for children with PHES. He expects that within the next five years there will be enough research data to change clinical practice and make it more consistent.
“Our findings also allow more targeted research into treatments for sepsis,” he said. “Studies might show that a treatment is ineffective for children with sepsis overall, but that same treatment could be studied in children with PHES and prove to be life-saving for this distinct group of patients.”
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute, which is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is a nonprofit organization committed to providing access to exceptional care for every child. It is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. Lurie Children’s is the pediatric training ground for Northwestern University Feinberg School of Medicine.

A rare supercentenarian, he remained remarkably lucid after 11 decades, even maintaining a blog. His brain has been donated for research on what’s known as super-aging.Morrie Markoff, a supercentenarian blogger and scrap-metal sculptor who was believed to be the oldest man in the United States and whose brain has been donated for research on what is known as super-aging, died on June 3 at his home in downtown Los Angeles. He was 110.He had two strokes in recent weeks, his daughter, Judith Markoff Hansen, said in confirming his death.People who live to be 110 or older are considered supercentenarians, and the Gerontology Research Group, in Los Angeles, lists more than 150 of them around the world.Mr. Markoff, who was born in New York City on Jan. 11, 1914, six months before World War I began, joined the club this year and was regarded as the oldest living man in the United States after the death in January of Francis Zouein, at 113, in California.As of April, the oldest living man in the world is believed to be John Alfred Tinniswood, of England, at 111, according to Guinness World Records. (Guinness lists María Branyas Morera, a California native who lives in Spain, as the oldest woman in the world, at 117.)When Mr. Markoff heard the news of his rise to the top of the list, “He just smiled and said, ‘Well, someone’s got to be there,’” his daughter said in an interview.We are having trouble retrieving the article content.Please enable JavaScript in your browser settings.Thank you for your patience while we verify access. If you are in Reader mode please exit and log into your Times account, or subscribe for all of The Times.Thank you for your patience while we verify access.Already a subscriber? Log in.Want all of The Times? Subscribe.

Investigators from UCLA Health found using artificial intelligence to help map out the boundaries of cancerous prostate tissue can significantly reduce the risk of underestimating the extent of prostate cancer — an advancement that can help ensure an accurate diagnosis, precise treatment planning and effective surgical procedures.
By using AI to assist with cancer contouring, the researchers found predicting the cancer size was 45 times more accurate and consistent than when physicians used only conventional clinical imaging and blood tests to predict the cancer extent.
The findings were published in the Journal of Urology.
“Accurately determining the extent of prostate cancer is crucial for treatment planning, as different stages may require different approaches such as active surveillance, surgery, focal therapy, radiation therapy, hormone therapy, chemotherapy, or a combination of these treatments,” said study author Dr. Wayne Brisbane, assistant professor of urology at the David Geffen School of Medicine at UCLA and member of the UCLA Health Jonsson Comprehensive Cancer Center.
Assessing the extent of prostate cancer is a complex task and typically requires a surgeon to consider various diagnostic tests such as a prostate-specific antigen (PSA) blood test, imaging tests like MRI, CT scans, and other clinical features simultaneously to determine the aggressiveness of the cancer cells.
Physicians tend to rely on a tumor’s MRI appearance, but the true extent of the prostate cancer can be “MRI-invisible” causing physicians to underestimate the tumor size, noted Brisbane. AI could help resolve this challenging problem.
The new AI system, developed by researchers at UCLA and Avenda Health, has already shown to better define the margins of prostate cancer than MRI, demonstrating the potential of AI to help improve minimally invasive treatment approaches like focal therapy, which is a relatively new approach for treating prostate cancer that aims to eliminate the cancer cells while minimizing damage to surrounding healthy tissue. However, prior to this study, characterizing the performance of the AI system in the hands of physicians was previously not tested.

In order to evaluate the cancer contouring and clinical decision-making of physicians with and without AI software, the researchers conducted a multi-reader-multi-case study that compared cognitive and hemi-gland contouring methodologies to AI-assisted contours.
Seven urologists and three radiologists from different hospitals with varying levels of experience ranging from two to 23 years reviewed cases of 50 patients who had undergone a prostatectomy but who might have been eligible for focal therapy.
Each case included images from a specific type of MRI scan called T2-weighted MRI, along with outlines of the prostate gland and areas where cancer was suspected, as well as a report from a biopsy.
First, the physicians looked at the images and manually drew outlines around the suspected cancerous areas, aiming to encapsulate all significant disease. Then, after waiting for at least four weeks, they reexamined the same cases, this time using AI software to assist them in identifying the cancerous areas.
An analysis was then completed to evaluate the accuracy and negative margin rate — which indicates whether all cancerous tissue was identified — of the cancer outlines drawn by each method.
The researchers found when using conventional means, doctors only achieved a negative margin 1.6% of the time. When assisted by AI the number increased to 72.8%.

“We saw the use of AI assistance made doctors both more accurate and more consistent, meaning doctors tended to agree more when using AI assistance,” said Shyam Natarajan, assistant adjunct professor of urology, surgery, and bioengineering and senior author of the study.
The team also found that the use of AI increased clinician recommendations for focal therapy among patients with unilateral cancer and reduced variation in accurate tumor encapsulation, which could help reduce the risk of side effects commonly associated with more aggressive treatments like surgery or radiation therapy.
“Overall, the use of AI in cancer treatment could lead to more effective and personalized care for patients, with treatments that are better tailored to their individual needs and more successful in fighting the disease,” said Brisbane.
The study was funded in part by the National Cancer Institute at the National Institutes of Health.
The study’s co-first authors are Sakina Mohammed Mota and Alan Priester, from Avenda Health. Other authors include James Sayre from UCLA and Joshua Shubert, Jeremey Bong and Brittany Berry-Pusey from Avenda Health.
Conflicts of Interest: Mota, Priester, Shubert, and Bong are employees of Avenda Health. Berry-Pusey and Natarajan are cofounders of Avenda Health. Sayre consults for Avenda Health.

We all know exercise is good.
It helps improve overall health and prevent disease. But the reasons why exercise does that haven’t been fully understood.
Enter Zhen Yan, professor with the Fralin Biomedical Research Institute at VTC and the College of Agriculture and Life Sciences at Virginia Tech, who helped discover thousands of alterations in bodies after various durations of endurance exercise training.
The Molecular Transducers of Physical Activity Consortium, of which Yan is a founding member, studied both male and female rats over eight weeks of endurance exercise and found thousands of molecular alterations. These findings, which published in May in Nature, have implications for human health, such as in liver disease, bowel disease, cardiovascular health, and tissue recovery.
“For most people in most situations, exercise is better than medicine,” said Yan, who is also director of the Fralin Biomedical Research Institute’s Center for Exercise Medicine Research and vice chairman of the International Research Group on Biochemistry of Exercise. “This data suggests that exercise can be a very potent and profound protection against diseases, such as nonalcoholic fatty liver disease, inflammatory bowel disease, and many others. This study unveiled things that we did not know, and I think it’s the beginning of revealing significant impacts of exercise in how it promotes health and prevents diseases.”
The National Institutes of Health funded the research. In addition to Yan, the study’s authors include Sarah Lessard, who in July will join the Fralin Biomedical Research Institute and the Department of Human Nutrition, Foods, and Exercise in the College of Agriculture and Life Sciences.
Is exercise better than medicine?
The Molecular Transducers of Physical Activity Consortium studied male and female rats over eight weeks of endurance exercise, examining changes in blood, plasma, and 18 solid tissues. Researchers analyzed nearly 10,000 samples using 25 molecular platforms at four training stages.

They found thousands of molecular changes, with differences between sexes in multiple tissues. These changes included regulation of immune, metabolic, stress responses, and mitochondrial pathways relevant to human health issues like nonalcoholic fatty liver disease, inflammatory bowel disease, cardiovascular health, and tissue recovery. Mitochondria are often referred to as the powerhouse of a cell as they aid in chemical energy as well as the regulation of a cell cycle, cell growth, and cellular health.
No single medicine could have such positive system-wide impacts and is as long-lasting, Yan said.
“Impact of exercise is far better than any single medicine,” he said. “There are studies showing that pregnancy exercise can even positively affect the grandchildren, and no single drug can do that.”
The path ahead
For Yan and the Molecular Transducers of Physical Activity Consortium, this research opened new doors. First is the need to expand the research to resistance-based exercise training — which could be weightlifting, resistance bands, or other methods of building muscle mass.
But it’s also important to truly understand the factors that mediate the molecular alterations.

“We need to dissect the health benefits that we’ve found so far,” Yan said. “I proposed a study that will analyze protein factors in the blood that are released by organs and tissues, such as the adrenal gland, muscles, and the heart, in response to a single bout of exercise and exercise training.”
Are these protein factors, or humoral factors, the true player in mediating the health benefit of exercise? How do they orchestrate coordinated cellular, biochemical and molecular responses in their target tissues and organs in achieving the superb health benefits of regular exercise?
Those are the burning questions, Yan said.
And those that he intends to answer.

When college athletes are evaluated for a possible concussion, the diagnosis is based on an athletic trainer or team physician’s assessment of three things: the player’s symptoms, physical balance and cognitive skills.
Research published today suggests that almost half of athletes who are ultimately diagnosed with a concussion will test normally on the recommended cognitive-skills test.
“If you don’t do well on the cognitive exam, it suggests you have a concussion. But many people who are concussed do fine on the exam,” said Dr. Kimberly Harmon, the study’s lead author. She is a professor of family medicine and section head of sports medicine at the University of Washington School of Medicine.
The study findings appear in JAMA Network Open.
Harmon said her sideline experiences as a team physician for the UW Huskies caused her to wonder how to accurately interpret the cognitive-screening portion of the Sport Concussion Assessment Tool (SCAT). Introduced in 2004 by the Concussion in Sport Group, the SCAT (now in its fifth iteration, SCAT5) was intended to standardize the gathering of information from athletes with a potential head injury.
The SCAT first prompts an athlete about whether they are experiencing any of 22 symptoms such as headache, nausea or blurred vision, and symptom severity. Then the tool tests the athlete’s cognition in several ways.
First come questions of orientation. (What day is it? What month is it?) Then a test of immediate memory, in which a list of 10 words is read aloud to the athlete, who is asked to restate the list. This sequence is repeated three times. Then the athlete’s concentration is tested by having to repeat short sequences of numbers in reverse order. Then comes a prescribed evaluation of the athlete’s balance, after which the athlete is again asked to recall the 10 words from the first list.

In Harmon’s experience as a team physician, she saw that “some people were concussed and they did well on the recall tests. Some people weren’t concussed and they didn’t do well. So I thought we should study it,” she said.
The study involved 92 NCAA Division I athletes who sustained a concussion between July 13, 2020, and Dec. 31, 2022, and who had a concussion evaluation within 48 hours. The investigators also recruited 92 of the concussed players’ teammates as matched control subjects, each of whom was given the SCAT5 screening within two weeks of the incident concussion.
All athletes in the study had previously completed NCAA-required baseline concussion screenings. The investigators found no significant differences in baseline scores between the athletes with and without concussion.
Harmon and colleagues analyzed the study participants’ SCAT5 responses and found that the word-recall tests had little predictive value for concussion. In fact, almost half (45%) of the concussed athletes performed at or above their baseline cognitive-test results, the researchers reported.
Instead, the study showed that the most accurate predictor of concussion were the athletes’ responses to questions about their symptoms.
“If you get hit in the head and go to the sideline and say, ‘I have a headache. I’m dizzy. I don’t feel right,’ I can say with pretty good assurance that you have a concussion,” Harmon said. “I don’t need to do any testing. The problem is that some athletes don’t want to come out. They don’t report their symptoms or may not recognize their symptoms. So then you need an objective, accurate test to tell you whether you can safely put the athlete back on the field. We don’t have that right now.”
During in-game evaluations for a concussion, team trainers and physicians must quickly synthesize the available evidence and make their best clinical judgment about a player’s health. The responsibility for a safety-first decision, though, also lies in part with the athletes, the study’s authors wrote:

“Although an increase in symptoms is highly suggestive of concussion, this relies on accurate reporting by the athlete who may not report symptoms because of a desire to return to play, a fear of letting teammates down, minimizing the seriousness of concussion, difficulty discerning symptoms, a delay in symptom development, or other reasons.”
“We are still short of the holy grail, which is an objective test for concussion,” Harmon said. “For now, this study shows how important it is for athletes to disclose their symptoms.”
The study was funded in part by the Jack and Luellen Cherneski and the Chisholm Foundation.

As long as humans have been traveling into space, astronauts have experienced significant health effects from the extreme conditions of space flight, notably the reduction of gravity.
Two Buck scientists led a team that has revealed for the first time how the lack of gravity affects the cells of the immune system at single cell resolution. As co-senior authors, along with Christopher E. Mason, PhD of Weill Cornell Medical College, Associate Professor David Furman, PhD and Associate Professor Daniel Winer, MD, published in the June 11, 2020 issue of Nature Communications an extensive survey of how gravity affects immune cells, and the identification of “space nutraceuticals” to counter aberrant effects of microgravity on these cells.
“We show how simulated microgravity shapes immune cells and how the changes in force alter the cells’ function at the single cell level,” said Winer. “This level of resolution is new and exciting in understanding the effects of microgravity on cells.”
Using cells in simulated microgravity, combined with data from space flight from astronauts and mice on the International Space Station, the researchers created a complete picture of how the different cells of the immune system in the peripheral blood are shaped by reduced gravity. These cells include lymphocytes and monocytes, which are the main players in immunity.
The study has potential implications for immune aging on Earth since the changes observed during aging resemble those captured during space travel.
The team additionally outlines a pathway for identifying compounds that can reverse the effects of near zero gravity, and demonstrates that one of the compounds, quercetin, shows promise for mitigating the damage caused by spaceflight and during normal aging on the ground.
“Our work provides a resource to better understand how and why the immune system changes in simulated microgravity and spaceflight,” said Furman. “We also provide a way to develop countermeasures to maintain normal immunity under these harsh conditions.”
Astronauts in low earth orbit, such as on the International Space Station, suffer from immune system problems, especially infections, latent viruses reactivating, and skin sensitivity. These reactions occur even on short-term spaceflights.

Previous studies using actual or simulated microgravity conditions have found impaired function of various immune cells. However, the fundamental mechanisms, genes, and pathways that explain immune dysfunction in microgravity were mostly unclear, the researchers said. They wanted to understand what was happening on a cellular level to explain the changes.
The team, led by the study’s co-first authors Buck postdoctoral researcher Fei Wu, PhD and graduate student Huixun Du, examined in depth how 25 hours of simulated microgravity affects the human peripheral blood mononuclear immune system, using samples from 27 healthy human donors between the ages of 20 and 46. To simulate an environment with almost no gravity, the team grew the cells inside of a Rotating Wall Vessel, a device developed by NASA to simulate microgravity conditions.
To explore the changes caused by reduced gravity, the team used a number of techniques, including sequencing and super-resolution microscopy. They then validated their findings by comparing their data with other space studies done in humans and mice, including the JAXA (Cell-Free Epigenome study) mission, SpaceX’s Inspiration 4 mission, NASA’s Twins Study, and spleens from mice housed on the International Space Station.
“Interestingly, changes in mechanical forces appear to orchestrate immune cell function,” said Winer, whose interest in studying space medicine grew from him delving into the emerging field of mechanoimmunology, or how environmental forces affect immune cell function. Parts of astroimmunology are related to mechanoimmunolgy, but it is proving its own as a new field, he said, paving the way to better understand how to help the immune system survive in space.
After unearthing several genes and biochemical pathways that are affected by microgravity, the team wanted to see if they could find any specific drugs or supplements that could protect the immune cells. To help them search, they used machine learning technology developed by Furman at the Buck, which can detect more than 2 million interactions between genes and different drugs and foods.
They identified dozens of potential compounds and chose one, the plant pigment quercetin (often found in red onions, grapes, berries, apples and citrus fruits among others) to explore further since it is widely available as an antioxidant and anti-aging supplement. Quercetin turned out to reverse approximately 70 percent of the changes caused by lack of gravity and protected the cells from reactive oxygen species excess.

“These findings define hallmarks of immune cell alteration in simulated microgravity, with correlation to spaceflight exposures in mice and humans,” said Winer. “This work helps define avenues for future research in mechanoimmunology and astroimmunology and provides opportunities to develop countermeasures to maintain normal cellular function in space.”
Furman adds that this publication sets the standard for how to analyze the physiological changes that accompany space travel. “This is the first comprehensive study that provides the scientific community worldwide with an atlas to understand human biology in this extreme condition,” he says.
“The implications are huge, beyond humans in space,” he adds. The researchers are excited to explore the parallel changes they are finding that occur in aging humans on the ground, and to use the knowledge to design interventions that can potentially reverse the immune dysfunction that accompanies aging.

The structure and function of the kidneys is altered by space flight, with galactic radiation causing permanent damage that would jeopardise any mission to Mars, according to a new study led by researchers from UCL.
The study, published in Nature Communications, is the largest analysis of kidney health in space flight to date and includes the first health dataset for commercial astronauts. It is published as part of a Nature special collection of papers on space and health.
Researchers have known that space flight causes certain health issues since the 1970s, in the years after humans first travelled beyond Earth’s magnetic field, most famously during the first moon landing in 1969. These issues include loss of bone mass, weakening of the heart and eyesight, and development of kidney stones.
It is thought that many of these issues stem from exposure to space radiation, such as solar winds from the Sun and Galactic Cosmic Radiation (GCR) from deep space, that the Earth’s magnetic field protects us from on Earth1. As most manned space flights take place in Low Earth orbit (LEO) and receive partial protection from Earth’s magnetic field, only the 24 people who have travelled to the moon have been exposed to unmitigated GCR and only for a short time (6-12 days).
Nobody has studied what changes might be happening in the kidneys and other organs as a result of conditions that would be experienced during space travel beyond Earth’s magnetic field over longer periods.
In this Wellcome, St Peters Trust and Kidney Research UK (KRUK) funded study, a UCL-led team of researchers from over 40 institutions across five continents conducted a range of experiments and analyses to investigate how the kidneys respond to space flight.
This included biomolecular, physiological and anatomical assessments using data and samples from 20 study cohorts. This included samples from over 40 Low Earth orbit space missions involving humans and mice, most of which were to the International Space Station, as well as 11 space simulations involving mice and rats.

Seven of these simulations involved mice exposed to simulated GCR doses equivalent to 1.5-year and 2.5-year Mars Missions, mimicking space flight beyond Earth’s magnetic field.
The results indicated that both human and animal kidneys are ‘remodelled’ by the conditions in space, with specific kidney tubules responsible for fine tuning calcium and salt balance showing signs of shrinkage after less than a month in space. Researchers say the likely cause of this is microgravity rather than GCR, though further research is required to determine if the interaction of microgravity and GCR can accelerate or worsen these structural changes.
The primary reason that kidney stones develop during space missions had previously been assumed to be solely due to microgravity-induced bone loss that leads to a build-up of calcium in the urine. Rather, the UCL team’s findings indicated that the way the kidneys process salts is fundamentally altered by space flight and likely a primary contributor to kidney stone formation.
Perhaps the most alarming finding, at least for any astronaut considering a three-year round trip to Mars, is that the kidneys of mice exposed to radiation simulating GCR for 2.5 years experienced permanent damage and loss of function.
Dr Keith Siew, first author of the study from the London Tubular Centre, based at the UCL Department of Renal Medicine, said: “We know what has happened to astronauts on the relatively short space missions conducted so far, in terms of an increase in health issues such as kidney stones. What we don’t know is why these issues occur, nor what is going to happen to astronauts on longer flights such as the proposed mission to Mars.
“If we don’t develop new ways to protect the kidneys, I’d say that while an astronaut could make it to Mars they might need dialysis on the way back. We know that the kidneys are late to show signs of radiation damage; by the time this becomes apparent it’s probably too late to prevent failure, which would be catastrophic for the mission’s chances of success.”
The authors say that though the results identify serious obstacles to a Mars mission, it is necessary to identify problems before solutions can be developed.

Professor Stephen B. Walsh, senior author of the study from the London Tubular Centre, UCL Department of Renal Medicine, said: “Our study highlights the fact that if you’re planning a space mission, kidneys really matter. You can’t protect them from galactic radiation using shielding, but as we learn more about renal biology it may be possible to develop technological or pharmaceutical measures to facilitate extended space travel.
“Any drugs developed for astronauts may also be beneficial here on Earth, for example by enabling cancer patients’ kidneys to tolerate higher doses of radiotherapy, the kidneys being one of the limiting factors in this regard.”
Though the study only describes what happens to the kidneys up to two and a half years, it is the most comprehensive data available for the time being.

Depressive symptoms are linked to subsequent memory decline in older people, while poorer memory is also linked to an increase in depressive symptoms later on, according to a new study led by researchers at UCL and Brighton and Sussex Medical School.
The study, published in JAMA Network Open, looked at 16 years of longitudinal data from 8,268 adults in England with an average age of 64.
The researchers concluded that depression and memory were closely interrelated, with both seeming to affect each other.
Senior author Dr Dorina Cadar, of the UCL Department of Behavioural Science & Health and Brighton and Sussex Medical School, said: “It is known that depression and poor memory often occur together in older people, but what comes first has been unclear.
“Our study shows that the relationship between depression and poor memory cuts both ways, with depressive symptoms preceding memory decline and memory decline linked to subsequent depressive symptoms.
“It also suggests that interventions to reduce depressive symptoms may help to slow down memory decline.”
Lead author Jiamin Yin, who graduated from UCL and is now a doctoral student at the University of Rochester, New York, said: “These findings underscore the importance of monitoring memory changes in older adults with increasing depressive symptoms to identify memory loss early and prevent further worsening of depressive function.

“Conversely, it is also critical to address depressive symptoms among those with memory decline to protect them from developing depression and memory dysfunction.”
The research team suggested that depression might affect memory due to depression-related changes in the brain. These include neurochemical imbalances (e.g. lower levels of serotonin and dopamine), structural changes in regions involved in memory processing, and disruptions to the brain’s ability to re-organise and form new connections.
The team said that memory impairments also might arise from psychological factors such as rumination — that is, repetitive thinking or dwelling on negative feelings.
On the other hand, people experiencing memory lapses or difficulties in retaining new information can lead to frustration, loss of confidence, and feelings of incompetence, which are common triggers for depressive episodes. Memory impairment may also disrupt daily functioning and social interactions, leading to social isolation potentially triggering depressive symptoms.
Dr Cadar added: “Depression can cause changes in brain structures, such as the hippocampus, which is critical for memory formation and retrieval. Chronic stress and high levels of cortisol associated with depression can damage neurons in these areas. However, a further understanding of mechanisms linking memory decline and depression is crucial for developing targeted interventions aimed at improving mood and slowing cognitive decline in individuals with depression and memory impairment.”
For this study, the researchers looked at data from the English Longitudinal Study of Ageing (ELSA), in which a nationally representative population sample in England answers a wide range of questions every two years.

People who started with higher depressive symptoms were more likely to experience faster memory decline later, while those who started with poorer memory were more likely to experience a later increase in depressive symptoms.
In addition, participants who experienced more of an increase in depressive symptoms during the study were more likely to have a steeper memory decline at the same time, and vice versa — those who had a steeper memory decline were more likely to have a sharper increase in depressive symptoms.
The same pattern was not found for verbal fluency. While less verbal fluency was linked to more depressive symptoms at the start of the study, changes in one did not predict later changes in the other.
The researchers accounted for a range of factors that might have affected the results, such as physical activity and life-limiting illness. As an observational study, the researchers noted, it could not establish causality.
The study and its authors received support from the National Institute on Aging, the Economic and Social Research Council (ESRC), the National Institute for Health and Research (NIHR), Alzheimer’s Society UK, and Alzheimer’s Research UK.

Fungal infections pose life-threatening risks, especially when vital organs or the central nervous system are affected. Individuals harboring variants in the CARD9 gene are particularly susceptible to invasive fungal infections, given that the protein coded by this gene serves as a critical regulator of the immune system. A recent discovery by Tokyo Medical and Dental University (TMDU) researchers suggests that a specific variant of CARD9 prevalent across northern China, Korea, and Japan may have originated from a common ancestor.
In their study published on 17 May 2024 in the Journal of Clinical Immunology, the researchers from TMDU conducted genetic analyses on Japanese and Korean patients who suffered from severe or recurring fungal infections. Their goal was to shed light on the genetic and clinical traits of individuals affected by CARD9 deficiency in East Asia.
The study included a total of five patients who were deficient for CARD9. Among them, two Japanese patients were newly identified as carriers of biallelic variants of CARD9 via DNA sequencing conducted by the research team, prompted by their medical history of fungal infections. Notably, both of these patients, along with three other patients who had previously been investigated, two Korean and one Japanese, were identified as carriers of a CARD9 variant called c.820dup.
“The global distribution of CARD9 deficiency is biased, with high incidence in North Africa, the Middle East, and China. Notably, the distribution of CARD9 variants is also biased, with the c.820dup variant being relatively common in China,” explains Prof. Hirokazu Kanegane, the lead researcher of the study.
The fact that all five patients shared the same variant caught the researchers’ attention. They hypothesized that this scenario could be explained by the “founder effect,” where a variant becomes common in a population that originated from a small group of ancestors. To verify their hypothesis, the researchers performed haplotype analyses. Put simply, they examined groups of genes that are inherited together from a parent (haplotypes) to determine whether these genes were identical among the five patients and matched previously sequenced haplotypes from Chinese CARD9-deficient patients.
Interestingly, they found strong evidence suggesting that all haplotypes containing the c.820dup variant were exactly the same. With further statistical genetic analyses, the researchers estimated the age of the c.820dup variant itself, which turned out to be between 2,000 and 4,000 years. Remarkably, the estimated variant’s age and its distribution in Japan, Korea, and China are perfectly in line with the history of the East Asia region. “Modern Japanese and Koreans are believed to have a genetic background originating from northern China. During the late Neolithic to the Bronze Age, the migration of people from northern China to Korea and Japan spread rice and language. The origins of the variant identified in this study are consistent with this historical period,” remarks Prof. Kanegane. “We thus conclude that this variant originates from a common ancestor, estimated to have lived less than 4,000 years ago.”
Additionally, although the variant observed was the same, the clinical presentation of patients from Japan and Korea differed from that of Chinese patients according to medical records. More specifically, Chinese patients often suffered from black mold infections caused by the genus Phialophora, whereas none of the five patients from Japan and Korea exhibited such infections. The researchers ascribed this discrepancy to environmental factors, possibly related to the more rural lifestyle in northern China.
Together, the findings of this interdisciplinary study make important contributions to our knowledge of anthropology, genetics, and medicine, and shed light on how genetic variants can propagate across different regions and through generations.