The genetic advantage that helps some people stay sharp for life

 Among the known genetic factors tied to late-onset Alzheimer's disease (AD), one gene variant stands out as the strongest risk factor. That variant is APOE-ε4. Another form of the same gene, APOE-ε2, has been associated with a lower likelihood of developing Alzheimer's and is widely believed to offer some level of protection against the disease.

A large study published Jan. 16 in Alzheimer's & Dementia, The Journal of the Alzheimer's Association, set out to examine how often these two gene variants appear in a rare group known as super agers. Super agers are people age 80 or older whose memory and thinking abilities closely resemble those of adults who are 20 or 30 years younger. The research was led by investigators at Vanderbilt University Medical Center.Lower Frequency of Alzheimer's Risk Gene

The results showed a striking difference in genetic risk. Super agers were 68% less likely to carry APOE-ε4 when compared with individuals age 80 and older who had Alzheimer's dementia.

What stood out even more was the comparison with cognitively healthy peers. Super agers were still 19% less likely to carry APOE-ε4 than other adults in the same age group who showed normal cognitive aging.

"This was our most striking finding -- although all adults who reach the age of 80 without receiving a diagnosis of clinical dementia exhibit exceptional aging, our study suggests that the super-ager phenotype can be used to identify a particularly exceptional group of oldest-old adults with a reduced genetic risk for Alzheimer's disease," said Leslie Gaynor, PhD, assistant professor of Medicine in the Division of Geriatric Medicine. She led the study together with Alaina Durant, BS, a statistical genetic analyst in the Vanderbilt Memory and Alzheimer's Center.

Higher Levels of a Protective Gene Variant

Researchers also discovered another important genetic distinction. For the first time, super agers were shown to have a higher frequency of APOE-ε2, the gene variant linked to reduced Alzheimer's risk.

Compared with cognitively normal adults age 80 and older, super agers were 28% more likely to carry APOE-ε2. When compared with participants age 80 or older who had Alzheimer's dementia, super agers were 103% more likely to have this protective variant.

Largest Study of Super Agers to Date

This observational study included the largest number of super agers examined so far. The analysis drew on data from the Alzheimer's Disease Sequencing Project Phenotype Harmonization Consortium (ADSP-PHC), which is led by study co-author Timothy Hohman, PhD, professor of Neurology.

Source: ScienceDaily

This one gene may explain most Alzheimer’s cases

 A new analysis led by researchers at University College London suggests that Alzheimer's disease may depend far more on one gene than previously recognized. The study estimates that more than 90% of Alzheimer's cases might not develop without the influence of a single gene called APOE.

The researchers also found that the gene's impact extends beyond Alzheimer's alone. Their analysis indicates that nearly half of all dementia cases may also rely on APOE's contribution.Published in npj Dementia, the findings point to APOE and the protein it produces as a major yet often overlooked target for drug development. Targeting this gene could open the door to preventing or treating a large share of dementia cases worldwide.

Understanding the APOE Gene and Its Variants

Scientists have known for decades that APOE is linked to Alzheimer's disease. The gene comes in three common forms, or alleles, called ε2, ε3, and ε4. Each person carries two copies of the gene, which results in six possible combinations* of these variants.

Research dating back to the 1990s showed that people who carry one or two copies of the ε4 variant face a much higher risk of developing Alzheimer's compared with those who inherit two ε3 copies. By contrast, people with ε2 generally have a lower risk than ε3 carriers.

Why Scientists Say APOE's Role Has Been Underestimated

Lead author Dr. Dylan Williams (UCL Division of Psychiatry and Unit for Lifelong Health and Ageing at UCL) said: "We have long underestimated how much the APOE gene contributes to the burden of Alzheimer's disease. The ε4 variant of APOE is well recognized as harmful by dementia researchers, but much disease would not occur without the additional impact of the common ε3 allele, which has been typically misperceived as neutral in terms of Alzheimer's risk.

"When we consider the contributions of ε3 and ε4, we can see that APOE potentially has a role in almost all Alzheimer's disease. Consequently, if we knew how to reduce the risk that the ε3 and ε4 variants confer to people, we may be able prevent most disease from occurring."

The Largest Modeling Study of APOE's Population Impact

This research represents the most comprehensive modeling effort so far to estimate how many Alzheimer's and dementia cases across the population are tied to common APOE variants. The team combined evidence linking ε3 and ε4 to Alzheimer's, broader dementia diagnoses, and the brain changes that precede the disease.

Source: ScienceDaily

A natural aging molecule may help restore memory in Alzheimer’s

 Singapore ranks among the countries with the longest life expectancy in the world. Even so, many people spend close to their final ten years coping with poor health. Researchers at the Yong Loo Lin School of Medicine, National University of Singapore (NUS Medicine) are working to change that reality by studying whether the biological process of aging itself can be altered to prevent age-related conditions, including Alzheimer's disease.

In a study published in Aging Cell, scientists led by Professor Brian K Kennedy from the Department of Biochemistry and Chair of the Healthy Longevity Translational Research Programme (TRP), NUS Medicine, identified a promising role for calcium alpha-ketoglutarate (CaAKG). This naturally occurring and widely studied metabolite, known for its links to healthy aging, was found to restore key brain functions tied to memory that are disrupted in Alzheimer's disease.The research set out to determine whether CaAKG could improve synaptic plasticity in the Alzheimer's brain, restore memory-related signaling, protect neurons from early degeneration, and support healthier cognitive aging overall. These findings point toward a shift in medical thinking, opening the door to geroprotective strategies -- treatments that target the biology of aging itself rather than addressing symptoms one disease at a time.

Researchers See New Potential for Alzheimer's Treatment

"Our findings reveal the exciting potential of longevity compounds in addressing Alzheimer's disease," said Prof Kennedy. "The research suggests that safe, natural compounds like CaAKG may one day complement existing approaches to protect the brain and slow memory loss. Because AKG is already present in our bodies, targeting these pathways may offer fewer risks and broader accessibility. Thanks to that, we may have a powerful new strategy to delay cognitive decline and support healthy brain aging."

The study showed that CaAKG improves how brain cells communicate in Alzheimer's disease models. It helped repair weakened signaling between neurons and restored associative memory, one of the earliest cognitive abilities affected by Alzheimer's. Since AKG levels naturally decline with age, restoring this molecule could be a promising way to support brain health over time and reduce the risk of neurodegenerative disease.

How CaAKG Supports Learning and Brain Health

To uncover how CaAKG produces these effects, the research team examined long-term potentiation (LTP), a process that strengthens connections between neurons and is essential for learning and long-term memory. In Alzheimer's disease, LTP is severely disrupted. The researchers found that CaAKG restored this process to normal levels.

CaAKG also increased autophagy, the brain's internal "clean-up" system that removes damaged proteins and helps neurons stay healthy. The molecule acted through a newly identified pathway, improving neuronal flexibility by activating L-type calcium channels and calcium-permeable AMPA receptors, while avoiding NMDA receptors that are often impaired by amyloid buildup.

Importantly, CaAKG restored synaptic tagging and capture, a critical mechanism that allows the brain to link experiences and form associative memories. This suggests the compound may support not only basic memory function but also higher-level learning abilities that tend to decline early in Alzheimer's disease.

Linking Longevity Science to Brain Protection

"Our goal was to determine whether a compound originally explored for extending healthy lifespan could be helpful for Alzheimer's disease," said Dr. Sheeja Navakkode, first author of the study and research scientist at Healthy Longevity TRP, NUS Medicine. "Understanding the cellular mechanisms of how CaAKG improves synaptic plasticity sheds light on new ways to protect memory and slow brain aging."

Source: ScienceDaily

Alzheimer’s may trick the brain into erasing its own memories

 Alzheimer's disease is known for one devastating effect above all others. It steadily destroys brain cells and the connections between them, breaking down the neural networks that allow us to store and recall memories.

What remains far less certain is how this destruction begins. One leading explanation focuses on amyloid beta, a protein fragment that can accumulate in the brain and harm neurons. But scientists have also linked Alzheimer's to many other factors, including tau proteins, lysosomes, chronic inflammation, immune cells called microglia, and additional biological processes.A Possible Link Between Two Major Theories

Researchers now believe they may have found a way to connect two of the most prominent ideas about how Alzheimer's develops. In a study published in Proceedings of the National Academy of Sciences, scientists report new evidence that amyloid beta and inflammation may act through the same molecular pathway. Both appear to converge on a specific receptor that signals neurons when to eliminate synapses, the contact points that allow brain cells to communicate.

The research was led by Wu Tsai Neurosciences Institute affiliate Carla Shatz, the Sapp Family Provostial Professor, along with first author Barbara Brott, a research scientist in Shatz's laboratory. The work received partial support from a Catalyst Award from the Knight Initiative for Brain Resilience, a program focused on reexamining the basic biology behind neurodegenerative diseases such as Alzheimer's.

The Role of a Synapse Pruning Receptor

One major component of the study builds on earlier work involving a receptor known as LilrB2. Shatz has studied this molecule for years. In 2006, she and her colleagues discovered that the mouse version of LilrB2 plays an essential role in synaptic pruning, a normal process during brain development and learning in adulthood.

Later findings connected this same receptor to Alzheimer's. In 2013, Shatz's team showed that amyloid beta can bind to LilrB2. When this happens, neurons are triggered to remove synapses. Importantly, experiments also showed that removing the receptor genetically protected mice from memory loss in an Alzheimer's disease model.

Inflammation and the Complement Cascade

The second major line of research examined an immune process known as the complement cascade. Under healthy conditions, this system releases molecules that help the body eliminate viruses, bacteria, and damaged cells.

Source: ScienceDaily

The simplest way teens can protect their mental health

 Sleeping in on weekends to make up for lost sleep during the week may offer mental health benefits for teenagers and young adults, according to new research from the University of Oregon and the State University of New York Upstate Medical University.

The study found that people ages 16 to 24 who caught up on sleep over the weekend were significantly less likely to report symptoms of depression. Compared with those who did not recover sleep on weekends, this group showed a 41 percent lower risk of depressive symptoms.The findings, published in the Journal of Affective Disorders, add to growing evidence that sleep plays a critical role in adolescent mental health. Teens and young adults face ongoing sleep challenges while also being at higher risk for depression, yet this age group has rarely been examined in studies focused on weekend catch-up sleep.

Why Weekend Sleep May Matter for Teens

This research offers one of the first looks at weekend catch-up sleep among typical adolescents and young adults in the United States. Earlier studies on the topic focused largely on school-age teens in China and Korea.

Many U.S. teens accumulate sleep debt during the school week as they juggle academic demands, social activities, extracurricular commitments, and in many cases part-time jobs.

"Sleep researchers and clinicians have long recommended that adolescents get eight to 10 hours of sleep at a regular time every day of the week, but that's just not practical for a lot of adolescents, or people generally," said Melynda Casement, a licensed psychologist, associate professor in the UO's College of Arts and Sciences and director of the UO's Sleep Lab. She co-authored the paper with Jason Carbone, assistant professor of public health and preventive medicine and of family medicine at the State University of New York Upstate Medical University.

While the researchers stress that consistently getting eight to 10 hours of sleep each night remains the ideal goal, they also recognize that it is often unrealistic. When teens cannot meet that target during the week, sleeping longer on weekends may help reduce the risk of depressive symptoms.

"It's normal for teens to be night owls, so let them catch up on sleep on weekends if they can't get enough sleep during the week because that's likely to be somewhat protective," Casement said.

How the Study Measured Sleep and Mood

The researchers analyzed data from 16- to 24-year-olds who participated in the 2021-23 National Health and Nutrition Examination Survey. Participants reported their typical bedtimes and wake-up times on weekdays and weekends.

Source: ScienceDaily

One protein may decide whether brain chemistry heals or harms

 Tryptophan is widely known for its connection to sleep, but its importance goes much further. The compounds produced from tryptophan help build proteins, generate cellular energy (NAD+), and create essential brain chemicals such as serotonin and melatonin. Together, these processes support mood, learning, and healthy sleep patterns.

As the brain ages or develops neurological disease, this system begins to break down. Scientists have repeatedly observed disruptions in how tryptophan is processed in aging brains, with even stronger effects seen in neurodegenerative and psychiatric disorders. These changes are linked to worsening mood, impaired learning, and disturbed sleep. Until now, however, researchers did not know what caused the brain to shift how it uses tryptophan in the first place.

SIRT6 Identified as a Key Regulator of Brain Chemistry

Prof. Debra Toiber and her research team at Ben-Gurion University of the Negev have now uncovered a clear biological explanation. Their work points to the loss of a longevity-related protein called Sirtuin 6 (SIRT6) as the driving factor behind this metabolic imbalance.

Using experiments in cells, Drosophila (fly), and mouse models, the researchers showed that SIRT6 plays an active role in controlling gene expression (e.g., TDO2, AANAT). When SIRT6 levels drop, this control is lost. As a result, tryptophan is redirected toward the kynurenic pathway, which produces neurotoxic compounds, while the production of protective neurotransmitters such as serotonin and melatonin declines.

Published Evidence and a Reversible Effect

The findings were recently published in Nature Communications.

Importantly, the researchers also found that the damage caused by this shift is not permanent. In a SIRT6 knockout fly model, blocking the enzyme TDO2 led to a significant improvement in movement problems and reduced the formation of vacuoles, which are signs of brain tissue damage. These results suggest that there may be a meaningful window for therapeutic intervention.

"Our research positions SIRT6 as a critical, upstream drug target for combating neurodegenerative pathology," says Prof. Toiber.

Research Team and Funding Support

Additional researchers include: Shai Kaluski-Kopatch, Daniel Stein, Alfredo Garcia Venzor, Ana Margarida Ferreira Campos, Melanie Planque, Bareket Goldstein, Estefanía De Allende-Becerra, Dmitrii Smirnov, Adam Zaretsky, Dr Ekaterina Eremenko -- Sgibnev, Miguel Portillo, Monica Einav, Alena Bruce Krejci, Uri Abdu, Ekaterina Khrameeva, Daniel Gitler, and Sarah-Maria Fendt.

The study was supported by the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (grant agreement No 849029), the David and Inez Myers foundation, the Israeli Ministry of Science and Technology (MOST), the High-tech, Bio-tech and Negev fellowships of Kreitman School of Advanced Research of Ben-Gurion University and The Israel Science Foundation (Grant no. 422/23). The RNA-seq data analysis was supported by the Russian Science Foundation (grant number 25-71-20017).

Source: Science Daily

Massive brain study reveals why memory loss can suddenly speed up with age

 An unprecedented international research effort combining brain imaging and memory testing from thousands of adults is offering a clearer picture of how age-related brain changes affect memory. By bringing together data from multiple long-running studies, scientists were able to examine how memory performance shifts alongside structural changes in the brain over time.

The analysis drew on more than 10,000 MRI scans and over 13,000 memory assessments from 3,700 cognitively healthy adults across 13 separate studies. The results -- which tracked people across a wide age range -- reveal that the link between brain shrinkage and memory decline is not simple or linear. The association grows stronger in later life and cannot be explained only by well-known genetic risk factors for Alzheimer's disease, including APOE ε4. Together, the findings suggest that brain aging involves complex, widespread changes rather than damage driven by a single cause.

Memory Decline Reflects Widespread Brain Changes

Published in Nature Communications, the study titled "Vulnerability to memory decline in aging revealed by a mega-analysis of structural brain change" shows that memory-related brain changes extend far beyond one isolated region. Although the hippocampus showed the strongest connection between volume loss and declining memory, many other areas of the brain were also involved.

Both cortical and subcortical regions demonstrated meaningful relationships between structural decline and memory performance. Rather than pointing to failure in a single brain structure, the findings indicate a distributed vulnerability across the brain. Researchers observed a gradual pattern across regions, with the hippocampus showing the largest effects and smaller but still significant associations appearing across much of the brain.

A Nonlinear Pattern With Accelerating Effects

The researchers also found that the relationship between brain atrophy and memory loss varied widely between individuals and followed a nonlinear pattern. People who experienced faster-than-average structural brain loss showed much steeper declines in memory. This suggests that once brain shrinkage passes a certain level, its impact on memory increases more rapidly instead of progressing at a steady pace.

This accelerating effect appeared across many brain regions, not just the hippocampus. The consistency of this pattern supports the idea that memory decline during healthy aging reflects large-scale and network-level structural changes. While the hippocampus remains especially sensitive, it functions as part of a broader system rather than acting alone.

What the Findings Mean for Understanding Aging

"By integrating data across dozens of research cohorts, we now have the most detailed picture yet of how structural changes in the brain unfold with age and how they relate to memory," said Alvaro Pascual-Leone, MD, PhD, senior scientist at the Hinda and Arthur Marcus Institute for Aging Research and medical director at the Deanna and Sidney Wolk Center for Memory Health.

"Cognitive decline and memory loss are not simply the consequence of aging, but manifestations of individual predispositions and age-related processes enabling neurodegenerative processes and diseases. These results suggest that memory decline in aging is not just about one region or one gene -- it reflects a broad biological vulnerability in brain structure that accumulates over decades. Understanding this can help researchers identify individuals at risk early, and develop more precise and personalized interventions that support cognitive health across the lifespan and prevent cognitive disability."

International Collaboration Behind the Study

In addition to Pascual-Leone, the research team included Didac Vidal-Piñeiro, PhD, professor of psychology, University of Oslo; Øystein Sørensen, PhD, research scientist, University of Oslo; Marie Strømstad, MSc, Researcher, University of Oslo; Inge K. Amlien, PhD, senior researcher, University of Oslo; William F.C. Baaré, PhD, senior researcher, Danish Research Centre for Magnetic Resonance; David Bartrés-Faz, PhD, professor, University of Barcelona; Andreas M. Brandmaier, PhD, senior researcher, Max Planck Institute for Human Development; Gabriele Cattaneo, PhD, researcher, University of Milan; Sandra Düzel, Dr. rer. nat. (PhD), senior research scientist in the Center for Lifespan Psychology at the Max Planck Institute for Human Development; Paolo Ghisletta, PhD, professor, University of Geneva; Richard N. Henson, PhD, professor, University of Cambridge; Simone Kühn, PhD, senior scientist, Max Planck Institute for Human Development; Ulman Lindenberger, PhD, director, Max Planck Institute for Human Development; Athanasia M. Mowinckel, PhD, researcher, University of Oslo; Lars Nyberg, PhD, professor, Umeå University; James M. Roe, PhD, research scientist, University of Oslo; Javier Solana-Sánchez, PhD, postdoctoral fellow, University of Oslo; Cristina Solé-Padullés, PhD, researcher, University of Barcelona; Leiv Otto Watne, MD, PhD, neurologist, Oslo University Hospital; Thomas Wolfers, PhD, senior researcher, University of Oslo; Kristine B. Walhovd, PhD, professor, University of Oslo; and Anders M. Fjell, PhD, professor, University of Oslo.

Source: ScienceDaily

How cancer disrupts the brain and triggers anxiety and insomnia

 "The brain is an exquisite sensor of what's going on in your body," says Cold Spring Harbor Laboratory Assistant Professor Jeremy Borniger. "But it requires balance. Neurons need to be active or inactive at the right times. If that rhythm goes out of sync even a little bit, it can change the function of the entire brain."

That balance relies on carefully timed patterns of activity. When those patterns slip, even slightly, the brain's ability to regulate the body can be disrupted in wide-ranging ways.

Breast Cancer Alters Daily Stress Hormone Cycles

In studies involving mice, Borniger's lab discovered that breast cancer interferes with normal diurnal rhythms, meaning the natural day and night cycle of stress hormone release. In rodents, this hormone is corticosterone. In humans, it is cortisol. Under healthy conditions, these hormone levels rise and fall at predictable times throughout the day.

The researchers found that breast tumors flattened this normal pattern. Instead of fluctuating, corticosterone levels stayed unnaturally even. This loss of rhythm was linked to poorer quality of life and higher mortality in the mice.

Early Disruption of the Brain's Stress System

Disrupted daily rhythms are already known to contribute to stress-related problems such as insomnia and anxiety, which are common among people with cancer. These rhythms are regulated by a feedback network known as the HPA axis. The hypothalamus (H), pituitary gland (P), and adrenal glands (A) work together to keep stress hormones on a healthy schedule.

What surprised Borniger was how early this disruption appeared. In mice, breast cancer altered stress hormone rhythms before tumors could be physically detected. "Even before the tumors were palpable, we see about a 40 or 50% blunting of this corticosterone rhythm," he said. "We could see that happening within three days of inducing the cancer, which was very interesting."

Resetting Brain Rhythms Restores Immune Response

Closer examination of the hypothalamus revealed that certain neurons were stuck in a state of constant activity but produced weak signals. When researchers stimulated these neurons to recreate a normal day and night pattern, stress hormone rhythms returned to normal.

This reset had a striking effect. Anti-cancer immune cells began moving into breast tumors, and the tumors shrank substantially. Borniger explains:

"Enforcing this rhythm at the right time of day increased the immune system's ability to kill the cancer -- which is very strange, and we're still trying to figure out exactly how that works. The interesting thing is if we do the same stimulation at the wrong time of day, it no longer has this effect. So, you really need to have this rhythm at the right time to have this anti-cancer effect."

Improving Physiology to Support Cancer Treatment

The research team is now working to understand how tumors disrupt the body's normal rhythms in the first place. Borniger believes this line of research could eventually strengthen existing cancer treatments.

"What's really cool is that we didn't treat the mice with anti-cancer drugs," he says. "We're focused on making sure the patient is physiologically as healthy as possible. That itself fights the cancer. This might one day help boost the effectiveness of existing treatment strategies and significantly reduce the toxicity of many of these therapies."

Source: ScienceDaily

A brain glitch may explain why some people hear voices

 A new study led by psychologists at UNSW Sydney offers the clearest evidence so far that hearing voices in schizophrenia may arise from a breakdown in how the brain recognizes its own inner voice. The research suggests that the brain may be misidentifying internally generated thoughts as sounds coming from the outside world.

Published in the journal Schizophrenia Bulletin, the study also points toward a possible path for identifying biological markers of schizophrenia. This is important because there are currently no blood tests, brain scans, or lab based biomarkers (signs in the body that can tell us something about our health) that uniquely identify the condition.

Professor Thomas Whitford of the UNSW School of Psychology has spent years studying how inner speech works in both healthy individuals and people living with schizophrenia spectrum disorders.

"Inner speech is the voice in your head that silently narrates your thoughts - what you're doing, planning, or noticing," he says.

"Most people experience inner speech regularly, often without realizing it, though there are some who don't experience it at all.

"Our research shows that when we speak - even just in our heads - the part of the brain that processes sounds from the outside world becomes less active. This is because the brain predicts the sound of our own voice. But in people who hear voices, this prediction seems to go wrong, and the brain reacts as if the voice is coming from someone else."

Brainwaves Reveal a Longstanding Theory

According to Prof. Whitford, these findings strongly support a theory that has existed in mental health research for decades: that auditory hallucinations in schizophrenia may result from a person's own inner speech being mistaken for external speech.

"This idea's been around for 50 years, but it's been very difficult to test because inner speech is inherently private," he says.

"How do you measure it? One way is by using an EEG, which records the brain's electrical activity. Even though we can't hear inner speech, the brain still reacts to it - and in healthy people, using inner speech produces the same kind of reduction in brain activity as when they speak out loud.

"But in people who hear voices, that reduction of activity doesn't happen. In fact, their brains react even more strongly to inner speech, as if it's coming from someone else. That might help explain why the voices feel so real."

Testing How the Brain Predicts Sound

To explore this effect, the researchers divided participants into three groups. The first included 55 people with schizophrenia spectrum disorders who had experienced auditory verbal hallucinations (AVH) within the past week. The second group included 44 people with schizophrenia who either had no history of AVH or had not experienced them recently. The third group consisted of 43 healthy individuals with no history of schizophrenia.

Each participant wore an EEG (electroencephalography) cap while listening to sounds through headphones. At specific moments, they were asked to imagine saying either 'bah' or 'bih' silently in their minds while hearing one of those same sounds played aloud. Participants did not know in advance whether the sound they imagined would match what they heard.

In healthy participants, brain activity dropped when the imagined syllable matched the sound played through the headphones. This reduced response appeared in the auditory cortex, the region responsible for processing sound and speech. The pattern suggests the brain correctly predicted the sound and lowered its response, similar to what happens during normal speech.

The opposite pattern appeared in participants who had recently experienced auditory hallucinations. Instead of showing reduced activity, their brains reacted more strongly when the imagined sound matched what they heard.

"Their brains reacted more strongly to inner speech that matched the external sound, which was the exact opposite of what we found in the healthy participants," Prof. Whitford says.

"This reversal of the normal suppression effect suggests that the brain's prediction mechanism may be disrupted in people currently experiencing auditory hallucinations, which may cause their own inner voice to be misinterpreted as external speech."

Participants in the second schizophrenia group, those without recent hallucinations, showed brain responses that fell between the healthy group and the hallucinating group.

Source: ScienceDaily

Patients tried everything for depression then this implant changed their lives

 About one in five adults in the United States will experience major depression at some point in their lives. Many people improve after trying a few treatments, but for as many as one-third of patients, standard antidepressants or psychotherapy do not provide enough relief. This condition, known as treatment-resistant depression, can persist for years or even decades. New research now suggests that a small implanted device may offer meaningful and long-lasting improvement for people with the most severe forms of the illness.

Scientists at Washington University School of Medicine in St. Louis led a large, multicenter clinical trial to evaluate this approach. The researchers found that a device designed to stimulate the vagus nerve was linked to sustained improvements in depressive symptoms, daily functioning, and overall quality of life. For most patients who showed improvement after one year, those gains continued for at least two years.

The participants in the study had lived with depression for an average of 29 years and had already tried about 13 treatments without success. These included intensive options such as electroconvulsive therapy and transcranial magnetic stimulation, highlighting just how difficult their condition had been to treat.

The latest results come from the ongoing RECOVER trial and were published Jan. 13 in the International Journal of Neuropsychopharmacology.

"We believe the sample in this trial represents the sickest treatment-resistant depressed patient sample ever studied in a clinical trial," said lead author Charles Conway, MD, a professor of psychiatry and director of the WashU Medicine Treatment Resistant Mood Disorders Center. "There is a dire need to find effective treatments for these patients, who often have no other options. With this kind of chronic, disabling illness, even a partial response to treatment is life-altering, and with vagus nerve stimulation we're seeing that benefit is lasting."

How vagus nerve stimulation works

The RECOVER study was designed to test whether adding vagus nerve stimulation (VNS) to ongoing care could improve outcomes for people with treatment-resistant depression. The therapy involves surgically placing a device under the skin in the chest. The device sends carefully controlled electrical signals to the left vagus nerve -- a key communication pathway between the brain and many internal organs.

The VNS Therapy System is made by LivaNova USA, Inc., which sponsored and funded the RECOVER trial. The study is collecting long-term data on mood, daily function, and quality of life in people with severe treatment-resistant depression. One aim of the research is to help the U.S. Centers for Medicare and Medicaid Services (CMS) decide whether to expand coverage for the therapy. Because many private insurers follow CMS decisions, approval could make the treatment accessible to far more patients, as cost has been a major barrier.

Inside the RECOVER trial

Nearly 500 patients were enrolled across 84 locations in the United States. About three-quarters of participants were so severely affected by depression that they were unable to work. All patients received the implanted device, but only half had the device activated during the first year to allow for comparison. Researchers tracked changes in depression severity, quality of life, and everyday functioning.

A response was considered meaningful if symptoms improved by at least 30% compared with the start of the study. A reduction of 50% or more was classified as a "substantial" response.

Conway emphasized that even modest improvements can dramatically change a person's life. Severe depression can leave people feeling "paralyzed by life," unable to manage basic daily activities and at higher risk of hospitalization or early death.

Earlier findings from the blinded first year of the trial showed that patients with activated devices spent more time with improved mood, better functioning, and higher quality of life than those whose devices were not active. However, the primary measurement tool (the Montgomery-Åsberg depression scale, which measures the severity of depressive episodes) did not show a statistically significant difference between the two groups.

Benefits that last over time

In the newest analysis, the researchers focused on patients whose devices were active from the start of the trial. They wanted to see whether improvements seen at 12 months would continue through 24 months. They also examined whether some patients who did not improve in the first year might respond later with continued treatment.

Out of 214 patients who received active treatment from the beginning, about 69%, or 147 people, showed a meaningful response at one year in at least one outcome measure. Among those who benefited at 12 months, more than 80% maintained or improved their results by the two-year mark across measures of depression, quality of life, and daily functioning. For patients with a substantial response at one year -- defined as at least a 50% reduction in symptoms -- 92% were still benefiting at two years.

Source: ScienceDaily

Brain waves could help paralyzed patients move again

 People with spinal cord injuries often lose the ability to move their arms or legs. In many cases, the nerves in the limbs remain healthy, and the brain continues to function normally. The loss of movement happens because damage to the spinal cord blocks signals traveling between the brain and the body.

This disconnect has led researchers to search for ways to restore communication without repairing the spinal cord itself.

Testing EEG as a Noninvasive Solution

In a study published in APL Bioengineering by AIP Publishing, scientists from universities in Italy and Switzerland explored whether electroencephalography (EEG) could help bridge this gap. Their research focused on determining whether EEG could capture brain signals linked to movement and potentially reconnect them with the body.

When a person attempts to move a paralyzed limb, the brain still produces electrical activity associated with that action. If these signals can be detected and interpreted, they could be sent to a spinal cord stimulator that activates the nerves responsible for movement in that limb.

Moving Beyond Brain Implants

Most earlier studies relied on surgically implanted electrodes to record movement signals directly from the brain. Although these systems have shown encouraging results, the research team wanted to investigate whether EEG could offer a safer option.

EEG systems are worn as caps covered with electrodes that record brain activity from the scalp. While the setup may appear complex, the researchers say it avoids the risks involved with placing devices inside the brain or spinal cord.

"It can cause infections; it's another surgical procedure," said author Laura Toni. "We were wondering whether that could be avoided."

Challenges in Reading Movement Signals

Using EEG to decode movement attempts pushes the limits of current technology. Because EEG electrodes sit on the surface of the head, they struggle to capture signals that originate deeper within the brain.

This limitation is less problematic for movements involving the arms and hands. Signals controlling the legs and feet are harder to detect because they come from areas located closer to the center of the brain.

"The brain controls lower limb movements mainly in the central area, while upper limb movements are more on the outside," said Toni. "It's easier to have a spatial mapping of what you're trying to decode compared to the lower limbs."

Machine Learning Helps Interpret Brain Activity

To better analyze the EEG data, the researchers used a machine learning algorithm designed to work with small and complex datasets. During testing, patients wore EEG caps while attempting a series of simple movements. The team recorded the resulting brain activity and trained the algorithm to sort the signals into different categories.

The system successfully distinguished between moments when patients tried to move and when they remained still. However, it had difficulty telling different movement attempts apart.

What Future Research Could Achieve

The researchers believe their method can be improved with further development. They plan to refine the algorithm so it can recognize specific actions such as standing, walking, or climbing. The team also hopes to explore how these decoded signals could be used to activate implanted stimulators in patients recovering from spinal cord injuries.

If successful, this approach could move noninvasive brain scanning closer to helping people regain meaningful movement after paralysis.

Source: ScienceDaily

The hidden brain bias that makes some lies so convincing

 Detecting dishonesty requires people to interpret social cues, judge intent, and decide whether someone's words are trustworthy. Scientists have long wondered how we sort through this kind of social information and how we decide if someone is being honest. A key question is whether people evaluate information in the same way when it comes from a close friend or from someone they barely know.

To explore this, Yingjie Liu from North China University of Science and Technology led a research team investigating how people judge information depending on the relationship they share with the communicator.Studying Deception Through Brain Imaging

According to findings published in JNeurosci, the researchers used a neuroimaging method to observe brain activity in 66 healthy adults. Pairs of participants sat facing each other but interacted through computer screens, allowing the scientists to control the flow of information. Each message the participants exchanged had consequences that were described as either a "gain" or a "loss." A "gain" referred to information that benefited both individuals in the pair, while a "loss" referred to information that produced a negative outcome. Contributing researcher Rui Huang explained, "The key reason we chose 'gain' and 'loss' contexts is that they illustrate how people adjust decision-making in response to potential rewards or punishments."

The team discovered that people were more likely to trust false information during "gain" situations, and this behavior corresponded with activation in regions of the brain that process reward, assess risk, and interpret others' intentions. This suggests that the promise of a positive outcome can strongly influence whether a lie seems believable, even if the information should raise doubts.

Friends Show Unique Brain Patterns During Deception

One of the most striking findings involved the role of friendship. When the person delivering the potentially deceptive information was considered a friend, both individuals showed synchronized brain activity. This synchrony shifted depending on the context. For example, brain regions involved in reward showed greater alignment during "gain" scenarios, while regions tied to risk evaluation became more synchronized during "loss" moments. This shared activity provided enough information for researchers to predict when a participant was likely to be deceived by a friend.

Why People May Trust Rewarding Lies

Taken together, the results indicate that people may be especially vulnerable to believing lies when the information suggests the possibility of a "gain." The study also highlights how the brain processes social information differently between friends, which may make it harder to accurately judge the truthfulness of what is being said. This combination of reward-driven thinking and interpersonal connection appears to influence how people weigh honesty, potentially leading them to accept false information more easily in certain situations.

Source: ScienceDaily

Daily music listening linked to big drop in dementia risk

 Listening to music after the age of 70 appears to be associated with a meaningful reduction in dementia risk. A research team from Monash University analyzed data from more than 10,800 older adults and found that people in this age group who regularly listened to music experienced a 39 percent lower likelihood of developing dementia.

The project, led by Monash honours student Emma Jaffa and Professor Joanne Ryan, examined how both listening to music and playing instruments relate to cognitive health in adults over 70. Their analysis showed that individuals who consistently listened to music, compared with those who never, rarely, or only sometimes did so, had a 39 percent reduced risk of dementia. Playing an instrument was also tied to benefits, with a 35 percent reduction in dementia risk.

Findings Drawn From Large-Scale Aging Studies

Researchers based their work on information from the ASPirin in Reducing Events in the Elderly (ASPREE) study and the ASPREE Longitudinal Study of Older Persons (ALSOP) sub‐study. The results were published in the International Journal of Geriatric Psychiatry.

People who reported always listening to music demonstrated the strongest cognitive advantages. This group showed a 39 percent lower incidence of dementia and a 17 percent lower incidence of cognitive impairment, along with higher overall cognitive scores and better episodic memory (used when recalling everyday events). Those who both listened to and played music on a regular basis had a 33 percent reduced risk of dementia and a 22 percent reduced risk of cognitive impairment.

Music as an Accessible Activity for Brain Health

Ms Jaffa noted that the outcomes of the research "suggests music activities may be an accessible strategy for maintaining cognitive health in older adults, though causation cannot be established," she said.

The findings come at a time when population aging is creating new public health challenges. Longer life expectancy has led to rising rates of age‐related conditions, including cognitive decline and dementia, which places increasing pressure on families and healthcare systems.

Lifestyle Choices May Shape Cognitive Aging

Senior author Professor Ryan emphasized the urgency of exploring options to help delay or prevent dementia. "With no cure currently available for dementia, the importance of identifying strategies to help prevent or delay onset of the disease is critical," she said.

She added that "Evidence suggests that brain aging is not just based on age and genetics but can be influenced by one's own environmental and lifestyle choices. Our study suggests that lifestyle-based interventions, such as listening and/or playing music can promote cognitive health."

Source: ScienceDaily

A tiny ancient virus reveals secrets that could help fight superbugs

 A research effort led by Ōtākou Whakaihu Waka has generated an in-depth structural map of a bacteriophage, offering new insight into how these viruses could be used to counter drug-resistant bacteria.

Lead author Dr. James Hodgkinson-Bean, who completed his PhD in the Department of Microbiology and Immunology, says bacteriophages are "extremely exciting" to scientists searching for alternatives to antibiotics as antimicrobial resistance continues to rise."Bacteriophage viruses are non-harmful to all multi-cellular life and able to very selectively target and kill a target bacterium. Due to this, they are increasingly being researched and applied in 'phage therapy' to treat highly drug-resistant bacteria," he says.

He explains that bacteriophages are "exquisitely intricate viruses" that infect bacteria using large mechanical structures known as 'tails'.

3D Analysis Reveals How a Phage Attacks E. coli

The study, published in Science Advances, involved researchers from Otago and the Okinawa Institute of Science and Technology. They examined the structure of Bas63, a virus that infects E. coli, at a molecular scale to better understand how its tail functions during infection.

"This kind of research is important for understanding how we can select the optimal bacteriophages for therapies, and to understand the differences in infectious behavior we see in the lab," Dr. Hodgkinson-Bean says.

Senior author Associate Professor Mihnea Bostina, also from Otago's Department of Microbiology and Immunology, notes that rising antibiotic resistance and growing threats to global food security from plant pathogens make bacteriophages an increasingly valuable alternative.

"Our detailed blueprint of a bacteriophage advances rational design for medical, agricultural, and industrial applications, from treating infections to combating biofilms in food processing and water systems.

"Beyond science, the 3D data -- which shows the virus' rare whisker-collar connections, hexamer decoration proteins, and diverse tail fibers -- may inspire artists, animators, and educators."

Structural Clues Strengthen Understanding of Viral Evolution

According to Dr. Hodgkinson-Bean, insights into viral structure also help clarify how these viruses have evolved.

"While DNA generally serves as the best evolutionary marker in humans, the 3-dimensional structure of a virus is more informative of its distant evolutionary relationships with other viruses," he says.The team identified features that had previously only been seen in viruses that are very distantly related, revealing evolutionary connections that had not been documented before."We know through structural studies that bacteriophages are related to Herpes viruses -- this relationship is thought to extend back billions of years to before the emergence of multi-cellular life. For this reason, when we look at bacteriophage structure, we are looking at living fossils, primordial ancient beings."There is something truly beautiful about that."Building on Earlier DiscoveriesThis newly described structure is the second of its kind documented by the same research group. It follows an earlier investigation into pathogens responsible for potato diseases, which was recently published in Nature Communications.

Source: ScienceDaily

New DNA test predicts dangerous heart rhythms early

 A new DNA-based method from Northwestern Medicine can pinpoint hidden risks for arrhythmia and sudden cardiac death long before symptoms begin. Credit: Shutterstock

Key Points

• Researchers used whole genome sequencing to bring together monogenic and polygenic testing, two methods that are usually separated in both research and clinical practice.
• Experts say many more physicians should be using genetic testing, although a large portion of the medical workforce is not yet trained to interpret it.
• The results provide an early foundation for creating targeted treatments tailored to each person's unique genetic profile.

New Genetic Approach to Predicting Dangerous Heart Rhythms

In a new study from Northwestern Medicine, researchers have created a more refined genetic risk score that helps determine whether a person is likely to develop arrhythmia, a condition in which the heart beats irregularly. Arrhythmias can lead to serious medical problems, including atrial fibrillation (AFib) and sudden cardiac death.

The team reports that this improved method strengthens the accuracy of heart disease risk prediction while also offering a broad framework for genetic testing. According to the scientists, the same strategy could be adapted to assess other complex, genetically influenced conditions such as cancer, Parkinson's Disease and autism.

Building a More Complete Genetic Picture

"It's a very cool approach in which we are combining rare gene variants with common gene variants and then adding in non-coding genome information. To our knowledge, no one has used this comprehensive approach before, so it's really a roadmap of how to do that," said co-corresponding author Dr. Elizabeth McNally, director of the Center for Genetic Testing and a professor of medicine in the division of cardiology and of biochemistry and molecular genetics at Northwestern University Feinberg School of Medicine.

The researchers say their findings could support the development of targeted treatments shaped around an individual's full genetic profile. They also note that this type of analysis may allow clinicians to identify people at risk long before any symptoms arise.

The study, which analyzed data from 1,119 participants, was published on November 11 in Cell Reports Medicine.

Integrating Three Major Genetic Testing Methods

Current genetic testing typically falls into one of three separate categories:

• Monogenic testing: Identifies rare mutations in a single gene, similar to spotting a typo in a single word.
• Polygenic testing: Looks at many common gene variants to estimate overall risk, similar to examining the tone of a chapter.
• Genome sequencing: Reads the complete genetic code, much like reviewing an entire book.

"Genetic researchers, companies and geneticists often operate in silos," McNally said. "The companies that offer gene panel testing are not the same ones that provide polygenic risk scores."

In this study, the team combined information from all three genetic sources to produce a fuller view of disease risk. This integrated method uncovers rare mutations, evaluates cumulative genetic effects and reveals subtle patterns across the entire genome.

"When you sequence the whole genome, you can say, 'Let me look at this cardiomyopathy gene component, the gene panel and the polygenic component.' By combining the data together, you get a very high odds ratio of identifying who is at highest risk, and that's where we think this approach can really improve upon what is currently used," McNally said.

Why Physicians Need Greater Access to Genetic Testing

Cardiologists usually assess heart risk based on symptoms, family history and diagnostic tools such as EKGs, echocardiograms and MRIs. McNally said she also incorporates genetic testing into her patient evaluations.

"It helps me manage that patient better, know who's at greatest risk, and if we think the risk is really high, we'll recommend defibrillators for patients like that," McNally said. "Knowledge is power."

Despite the benefits, genetic testing remains underused. McNally said that only an estimated 1 to 5% of people who would benefit from genetic testing actually receive it. Even within cancer care, where genetic links are widely recognized, only 10 to 20% of eligible patients undergo testing.

Source: ScienceDaily