ROCHESTER, Minn. — Alzheimer's-related brain changes progressed up to 20 times faster in women who also had abnormal levels of a Parkinson's-related protein, according to a Mayo Clinic study published in JAMA Network Open. The same pattern was not observed in men.

The findings suggest that when alpha-synuclein — a protein linked to Parkinson's disease — accumulates alongside Alzheimer's pathology, it may drive faster disease progression in women. That interaction could help explain a long-standing disparity: women make up nearly two-thirds of people living with Alzheimer's disease in the U.S.

Kejal Kantarci, M.D., a Mayo Clinic neuroradiologist and senior author of the study, uses advanced brain imaging to track Alzheimer's progression.

"Recognizing these sex-specific differences could help us design more targeted clinical trials and ultimately more personalized treatment strategies," Dr. Kantarci says. "When we see disease-related changes unfolding at dramatically different rates, we cannot keep approaching Alzheimer's as though it behaves exactly the same way in everyone. Co-pathologies may impact the disease process."

Alzheimer's disease is marked by the buildup of tau protein in the brain. Many people along the Alzheimer's disease continuum also develop abnormal clumping of α-synuclein, a protein associated with Lewy body diseases such as Parkinson's disease and dementia with Lewy bodies.

Tau and α-synuclein occur naturally in the brain. In neurodegenerative diseases, however, these proteins can misfold and clump together, forming abnormal deposits. This pathological buildup disrupts communication between brain cells and contributes to cognitive decline.

Researchers set out to determine whether having both abnormal protein buildups alters how the disease progresses and whether that effect differs between women and men.

To investigate, the team analyzed data from 415 participants in the Alzheimer's Disease Neuroimaging Initiative, a national research consortium that tracks brain changes over time. Participants underwent cerebrospinal fluid testing to detect abnormal α-synuclein and repeated brain imaging to measure changes in tau accumulation. About 17% of participants showed evidence of abnormal α-synuclein.

Among participants with both Alzheimer's-related pathology and α-synuclein abnormalities, women accumulated tau dramatically faster than men with the same coexisting protein changes.

Elijah Mak, Ph.D., first author of the study and a Mayo Clinic neuroimaging researcher, studies how multiple brain pathologies interact and drive disease progression.

"This opens an entirely new direction for understanding why women bear a disproportionate burden of dementia," Dr. Mak says. "If we can unravel the mechanisms behind this vulnerability, we may uncover targets we haven't considered before."

The researchers are now examining whether these sex-specific effects also appear in patients with dementia with Lewy bodies, where α-synuclein is the primary disease driver rather than a coexisting pathology. The work will help determine whether the observed difference is unique to Alzheimer's disease or reflects a broader sex-specific vulnerability across neurodegenerative conditions.

For a complete list of authors, disclosures and funding, review the study.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

 Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

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JACKSONVILLE, Fla. — In a study published in Nature Communications, Mayo Clinic researchers have identified specific DNA-level changes in the brains of people with Alzheimer's disease (AD). Using advanced biological analysis, the team mapped alterations in the brain’s regulatory landscape that may help explain why Alzheimer's presents and progresses differently from person to person. The findings could also open new avenues for understanding other neurodegenerative diseases.

Alzheimer’s disease is the most common cause of dementia. Biologically, the disease begins with the formation of protein deposits, known as amyloid plaques, and neurofibrillary tangles in the brain. This causes brain cells to die over time and the brain to shrink. About 6.9 million people in the U.S. age 65 and older live with Alzheimer's disease. There is no cure, and in advanced stages, complications can result in a significant decline in quality of life and death.

The Mayo research team studied brain tissue from the Mayo Clinic Department of Neuroscience Brain Bank, examining brain tissue from 472 people with AD, and analyzed patterns of DNA methylation — a type of chemical "tag" on DNA — across the genome. These samples include detailed measurements of Alzheimer's-related changes — both the visible brain changes seen under a microscope and the levels of key AD proteins.

“While our study findings are impactful by themselves, we did not want to stop there and sought to make both our data and results available to the research community in a way that also protects donor identities," says Nilüfer Ertekin-Taner, M.D., Ph.D., chair of Neuroscience at Mayo Clinic, a physician-scientist and senior author of the study. "We wanted to do this because relatively few groups have the expertise to analyze such big data and derive biological insights."

Uncovering a myelin-related pathway in AD 

The findings suggest that in AD, part of what happens in the brain may involve changes in DNA tagging that affect the function of oligodendrocytes, particularly in relation to the buildup of the toxic protein tau.

Oligodendrocytes are the brain cells that make myelin, the insulation that helps nerve cells communicate. Scientists have theorized that disrupting neuron communication contributes to symptoms for people with AD. Researchers in this study found that nearly all significant methylation changes — small chemical tags added to DNA that help control when genes are turned on or off — were linked to the tau protein. This supports the idea that this protein plays a key role in brain cell changes tied to AD.

"Our team has previously shown that oligodendrocytes are affected in Alzheimer's and another tau-related disease, progressive supranuclear palsy (PSP)," says Dr. Ertekin-Taner. "These new results further highlight that problems in oligodendrocytes and myelin are central to AD. They also point to specific molecular pathways, particularly epigenetic changes, that could be targeted in future therapies."

Epigenetic changes are chemical tags on DNA that help control how genes are expressed, or turned on or off, without altering the genetic code itself. Because these changes influence how brain cells function and may be reversible. They offer promising targets for future Alzheimer’s treatments.

Opening the door for future research

The study results identified new genes that may play a role in AD, including one called LDB3, and confirmed many findings across multiple independent datasets, showing its reliability. The identification of specific genes provides potential targets for future research — for example, scientists might investigate whether interventions that reverse methylation or support oligodendrocyte health can slow or modify disease progression for patients with AD.

The Mayo research team also developed an interactive tool to help with digital searching of the dataset. Called the Multiomic Atlas of AD Brain Endophenotypes, this free application is a way to make information accessible and enable further research about AD and neurology. The dataset can be searched by gene name or chromosomal location, and results are presented in both table and interactive plot formats.

While this work will continue to shape research, its impact extends beyond Mayo Clinic and will provide a valuable resource for scientists worldwide. Stephanie Oatman, Ph.D., the study's lead author, conducted this work during her doctoral training in Dr. Ertekin-Taner's laboratory and is now a postdoctoral research fellow at Brigham and Women's Hospital.

"To build on our understanding of Alzheimer's disease and work toward helping people living with the disease, it's crucial that other researchers can easily access the comprehensive analyses we performed in this study," she says. "This shared access can amplify the impact of our research across different scientific fields and ultimately benefit patients."

For a complete list of authors, disclosures and funding, review the study.  

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

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DEAR MAYO CLINIC: My coworker had been telling me they were having pain in their lower back that extended down into their hips. They were diagnosed with a sacroiliac (SI) joint issue. I occasionally experience back pain myself and wonder whether surgical treatments are available for sacroiliac joint problems.

ANSWER: Yes, surgery can help relieve SI joint pain, but it’s usually considered only after the diagnosis has been confirmed and when nonsurgical treatments haven’t worked. Because back pain can come from many sources, finding the true cause is essential before considering surgery. When pain persists or affects daily life, evaluating the sacroiliac joint as a potential cause of the pain can help identify more effective treatment options.

Where is the sacroliac joint?

The sacroiliac joint sits between the base of the spine (the sacrum) and the pelvis. It is one of the body’s largest weight-bearing joints, helping transfer force from the upper body into the legs during activities such as standing, walking and lifting. Arthritis or excessive motion in the joint can lead to significant pain in the lower back, hips or buttocks, sometimes radiating into the legs.

SI joint pain can closely mimic conditions affecting the spine or hips, which makes diagnosis challenging. Research suggests that up to 15% to 30% of people with chronic low back pain may have pain originating from the SI joint. Some individuals live with symptoms for years or even undergo other procedures before the SI joint is correctly identified as the source.

Diagnosis typically begins with imaging to rule out other causes, such as infection or tumors. However, imaging alone is not enough. A physical exam that stresses the joint, followed by a diagnostic injection into the SI joint, helps confirm whether it’s truly responsible for the pain. If an injection significantly reduces your pain, it confirms that the SI joint is the cause.

Surgery isn’t the first step for SI joint pain. Most people begin with conservative treatments, including anti-inflammatory medications, physical therapy or therapeutic injections. These approaches aim to reduce inflammation, improve joint stability and relieve pain without surgery.

Physical therapy may help strengthen supporting muscles, while injections can provide temporary relief, sometimes lasting several weeks or months, although symptoms may return. Surgery is generally considered when pain has lasted longer than six months and hasn’t improved with nonsurgical care.

People with confirmed SI joint pain who don’t find relief through conservative treatments may be candidates for surgery. Certain conditions, such as widespread inflammatory arthritis or serious medical issues that make anesthesia unsafe, may rule out surgery. Smoking can also interfere with bone healing and affect surgical outcomes.

Modern SI joint surgery is typically minimally invasive. Through a small incision near the hip, surgeons place implants across the joint to stabilize it. The implants are relatively small and resemble screws, with specialized surfaces designed to encourage bone growth. Over time, bone grows across the joint, helping create lasting stability and reduce painful movement. The procedure often takes less than an hour, and some patients can return home the same day.

Most people have activity restrictions for about six weeks after surgery. Pain relief may be noticeable early, particularly when excessive joint motion was the cause, while arthritis-related pain may improve more gradually. By six months, about 80% of patients report improved quality of life and pain. Studies show these improvements can last for years.
 
If you’ve been told nothing can be done for chronic low back pain, don’t lose hope. For some people, SI joint pain may be the cause, and effective treatments, including surgery, are available. 

Grant W. Mallory, M.D., Neurosurgery, Mayo Clinic Health System, Eau Claire and La Crosse, Wisconsin

The post Mayo Clinic Q&A: Can surgery alleviate sacroiliac joint pain and issues? appeared first on Mayo Clinic News Network.

ROCHESTER, Minn. — The brain may inadvertently "learn" to have seizures by treating them like important memories to be stored, according to new research from Mayo Clinic.

The study, published in the Journal of Neuroscience, found that after a seizure, the brain enters a deep sleep state that mimics memory storage — and that this effect can persist into the following night's sleep. In effect, this "saves" the seizure's path like a normal memory, strengthening the disease. The findings suggest new opportunities to prevent epilepsy from worsening by targeting brain activity during the hours immediately following a seizure and during the subsequent night of sleep — a critical period when harmful brain changes may occur.

"Sleep is one of the brain's most powerful tools for learning and memory," says Vaclav Kremen, Ph.D., a neuroscientist and engineer at Mayo Clinic and lead author of the study. "What we're seeing is that after a seizure, the brain may be engaging the same biological processes used to consolidate memories, but instead reinforcing the networks that generate seizures."

Epilepsy affects an estimated 50 million people worldwide, and many patients continue to have seizures despite medication. Understanding the relationship between seizures and sleep could help explain why epilepsy can worsen over time and why memory, mood and sleep problems are common in people with the condition.

The study analyzed long-term brain recordings from implanted devices in 11 people with epilepsy. Using these recordings, researchers compared sleep patterns on nights following seizures to nights when no recent seizures occurred.

They found that after a seizure, the brain consistently entered a prolonged and intensified state of deep sleep, known as non-rapid eye movement (NREM) sleep. During this period, slow brain waves became stronger and steeper — key features of memory consolidation — particularly within the specific brain regions where seizures originate.

At the same time, rapid eye movement (REM) sleep, which is important for emotional processing and cognitive health, was reduced. On average, patients slept longer and spent more time in deep sleep after seizures, but they experienced less REM sleep compared with seizure-free nights.

The researchers call this process seizure-related consolidation, a phenomenon in which seizures appear to hijack the brain's normal learning mechanisms. Rather than helping the brain recover, this post-seizure sleep state may strengthen abnormal neural circuits, creating a vicious cycle in which each seizure increases the likelihood of future seizures.

"Instead of treating seizures as isolated events, this research shows they may actively shape the brain in ways that promote disease progression," says Dr. Kremen.

Importantly, the findings point to a potential new window for treatment — the hours and nights after a seizure — when targeted intervention could disrupt this harmful learning process.

"If we can safely intervene during this post-seizure window, we may be able to weaken seizure networks rather than reinforce them,” says Gregory Worrell, M.D., Ph.D., a neurologist at Mayo Clinic and senior author of the study.

These insights support Mayo Clinic's Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative, which aims to devise personalized neuromodulation therapies to prevent, treat, and potentially reverse neurological disease. By combining long-term brain sensing, advanced analytics and an understanding of how the brain adapts after seizures, the study highlights the potential for bioelectronic approaches to promote healthier brain function.

Future research will focus on translating these discoveries into BIONIC-enabled therapies, including adaptive closed-loop brain stimulation systems designed to respond to seizures and sleep states in real time. Mayo Clinic researchers have already begun designing next-generation approaches aimed at breaking this cycle and restoring normal brain activity.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post Brain may reinforce seizures during sleep, Mayo Clinic study suggests appeared first on Mayo Clinic News Network.

Jason Howland has more in this Mayo Clinic Minute.

Watch: The Mayo Clinic Minute

Journalists: Broadcast-quality video pkg (1:00) is in the downloads. Read the script.

Drive for show. Putt for dough. But when lining up that winning shot, it can be a golfer's greatest fear: a sudden case of the yips.

"The yips is a description given by people who golf of a twitch, or a jerk or involuntary movement when usually putting," says Dr. Charles Adler, a Mayo Clinic neurologist.

In many cases, the yips is thought to be psychological. A golfer under pressure experiencing performance anxiety is usually par for the course. But there are others that likely have a neurologic problem.

Yips as a neurologic problem

"We call it 'dystonia' or 'tremor.' It's an involuntary movement disorder," says Dr. Adler. "So only when performing a golf movement, such as moving the putter, does the involuntary movement come out."

Dr. Adler is teeing up the topic as lead author of a Mayo Clinic study on the yips, which could offer athletes improved treatment options.

"It's our belief that treatment is going to be different for people who have a neurologic cause and a nonneurologic cause."

Dr. Adler says more research is needed with the hope of finding specific treatment options to overcome the yips. And that would be a hole in one for every golfer on the green.

Related story: Behind the scenes of fan health: Mayo Clinic marks 25 years as WM Phoenix Open medical sponsor

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Watch: Dr. Worrell discusses advancing epilepsy care

 Journalists: Broadcast-quality sound bites are available in the downloads at the end of the post. Please courtesy: "Mayo Clinic News Network." Name super/CG: Gregory Worrell, M.D., Ph.D./ Neurology /Mayo Clinic.

Why is epilepsy such a challenging condition to treat? 
Epilepsy affects people across the entire lifespan, from infancy through older adulthood. About one-third of patients continue to have seizures despite medication. Many also experience disabling comorbidities such as sleep disturbances, memory problems and mood disorders. Treating epilepsy effectively requires addressing all of these challenges, not just seizures alone. 

How does a team-based approach improve epilepsy care? 
Addressing epilepsy requires collaboration across many specialties, including basic neuroscience, engineering, neurology, neurosurgery, neuroradiology and psychiatry. By combining expertise and leveraging advances in biology, imaging, engineering, computing and artificial intelligence, we can better meet the complex and unmet needs of patients.  

What is the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) Initiative, and why is it important for epilepsy care? 
The BIONIC initiative is focused on changing the course of epilepsy therapy and diagnostics. We're in a period of rapid technological acceleration — advances in artificial intelligence, neurotechnology, computing and connected devices. These tools allow us to deliver and adjust therapies in real time and to receive feedback from people with epilepsy as they go about their daily lives. This creates new opportunities to better understand epilepsy, create new therapies and improve patient care. 

How do these technologies help people living with epilepsy day to day? 
Today, we can track seizures as well as common epilepsy-related comorbidities such as sleep problems, memory issues and mood disorders. Importantly, we can also intervene using neuromodulation using electrical brain stimulation, to help suppress seizures and improve these comorbidities. This technology allows care to extend beyond the clinic and into a patient's home. 

What kinds of devices are being developed through BIONIC? 
We're developing a next-generation neuromodulation platform with devices that are fully implantable and integrated with wearables and computing. These devices include electrodes placed in the brain and have sensing capabilities that allow continuous recording of brain activity. The data can be securely transmitted through a handheld device to the cloud. The system enables analysis that can guide therapy and drive better understanding of seizures and related conditions. 

What can clinicians and researchers learn from this brain data? 
By continuously recording brain activity, we can track seizures, sleep patterns, memory and mood. This data allows us to adjust electrical therapies in a more personalized way. Ultimately, our goal is to forecast seizures before they happen and deliver adaptive therapies that prevent seizures before they occur and address the broader impact of epilepsy on daily life. 

How do these new devices compare to earlier generations? 
Earlier devices were groundbreaking for their time, but they had fewer capabilities. The devices we're preparing for clinical trials are significantly smaller, more powerful, rechargeable and offer expanded stimulation, sensing and streaming capabilities. This represents a major step forward in both technology and patient experience. 

What is the long-term vision of the BIONIC Initiative? 
Our vision is to build more effective therapies, prevent seizures before they occur and directly target comorbidities. With current newly developed technologies, these goals are now achievable, and BIONIC is focused on translating them into real-world patient benefits. 

Why is collaboration beyond Mayo Clinic essential? 
These challenges can't be solved by one person or one institution alone. Collaboration with other academic centers, industry partners and most importantly, patients is essential. A technology that doesn't have a clear path to commercialization, even if it's innovative, will likely only help a relatively small number of people. 

How do patients factor into the development of these therapies? 
Partnering with patients is critical. We need to understand what matters most to them and what they need to improve their quality of life. Their input helps guide technology development so that it truly addresses real-world needs. 

What is the ultimate goal of BIONIC? 
The goal of BIONIC is to bring all of these elements together into a unified effort to create the future of epilepsy therapy — one that is more personalized, proactive and focused on the whole patient. It is important to realize that the neuromodulation technologies developed for epilepsy will have a wide impact on many other diseases of the brain and mind. 
 
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About Mayo Clinic  
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.  

Media contact: 

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu  
   
   

The post Advancing epilepsy care: Mayo Clinic neurologist Dr. Gregory Worrell  appeared first on Mayo Clinic News Network.

These discoveries reflect progress across three major innovation efforts at Mayo Clinic. Mayo Clinic clinicians and scientists are working together to develop tools to predict and intercept biological processes before they evolve into disease or progress into complex, hard-to-treat conditions through the Precure initiative. They are advancing new cures for end-organ failure beyond traditional transplantation as part of the Genesis initiative. They are also uniting clinical insight with cutting-edge engineering to deliver novel neurological diagnostics and therapies through the Bioelectronics Neuromodulation Innovation to Cure (BIONIC) initiative. 
 

1. 'Virtual clinical trials' may predict success of heart failure drugs 

Mayo Clinic researchers have created "virtual clinical trials" that advance the discovery of therapies while reducing time, cost and the risk of failed studies by combining advanced computer modeling with real-world patient data as part of the Precure and Genesis initiatives. Through one virtual clinical trial, they have developed a new way to predict whether existing drugs could be repurposed to treat heart failure, one of the world's most pressing health challenges. 

"Clinical trials will always remain essential," says Cui Tao, Ph.D., the Nancy Peretsman and Robert Scully Chair of Artificial Intelligence and Informatics and vice president of Mayo Clinic Platform Informatics. "But this innovation demonstrates how AI can make research more efficient, affordable and broadly accessible. Integrating trial emulation, simulation, synthetic trials and biomedical knowledge modeling opens the door to a new paradigm in translational science." 

2. New discovery may unlock regenerative therapies for lung disease

Mayo Clinic researchers have uncovered the molecular "switch" that directs a small but powerful set of cells that choose whether to repair tissue or fight infection, a discovery that could inform regenerative therapies for chronic lung diseases, which is part of Mayo Clinic's Genesis initiative.
 
"We were surprised to find that these specialized cells cannot do both jobs at once," says Douglas Brownfield, Ph.D., senior author of the study. "Some commit to rebuilding, while others focus on defense. That division of labor is essential — and by uncovering the switch that controls it, we can start thinking about how to restore balance when it breaks down in disease." 

3. Stem cells may offer new hope for end-stage kidney disease treatment

Mayo Clinic researchers found that injecting patients' own stem cells from fat cells into the vein before hemodialysis, a treatment for end-stage kidney disease, often helped prevent inflammation and vein narrowing. This could help millions of people tolerate dialysis longer, extending the time before they require a kidney transplant as part of the Mayo Clinic Genesis initiative. 

"This approach has the potential to improve outcomes for millions of patients with kidney failure, reduce healthcare costs and inform new clinical guidelines for dialysis access management if validated in larger clinical trials," says Sanjay Misra, M.D., a Mayo Clinic interventional radiologist. 

4. Mayo Clinic physicians map patients' brain waves to personalize epilepsy treatment

Using detailed maps of each patient's unique brain wave patterns, Mayo Clinic physicians can now pinpoint where stimulation is most effective, moving beyond the traditional one-size-fits-all approach to epilepsy treatment. This research is part of the BIONIC initiative.

"The long-term goal is to quiet the seizure network, so it is eventually forgotten. Reorganizing the neuronal network could move us beyond controlling seizures to actually curing epilepsy," says Nick Gregg, M.D., a Mayo Clinic neurologist. 

5. New genetic biomarker flags aggressive brain tumors

Mayo Clinic researchers found when meningiomas — the most common type of brain tumor — show activity in a gene called telomerase reverse transcriptase (TERT), it tends to recur more quickly, even if it looks low grade under the microscope. This is part of the Mayo Clinic Precure initiative. 

"High TERT expression is strongly linked to faster disease progression," says Gelareh Zadeh, M.D., Ph.D., a neurosurgeon at Mayo Clinic and senior author of the study. "This makes it a promising new biomarker for identifying patients who may be at greater risk of developing aggressive disease."

6. Mayo Clinic researchers discover the immune system's 'fountain of youth'

Mayo Clinic researchers have found that some older people maintain "immune youth" – a new term coined by Mayo researchers to explain a young immune system in someone over age 60.  
 
"We observed that these patients have very young immune systems despite being in their 60s and 70s. But the price they pay for that is autoimmunity," says Cornelia Weyand, M.D., Ph.D., a Mayo Clinic rheumatologist and clinician-scientist. This is part of the Mayo Clinic Precure initiative.

7. Mayo Clinic tools predict, identify and diagnose Alzheimer's, dementia quicker

Mayo Clinic researchers have developed new tools to estimate a person's risk of developing Alzheimer's disease years before symptoms appear as part of the Precure initiative and to help clinicians identify brain activity patterns linked to nine types of dementia, including Alzheimer's disease, using one scan. They also confirmed the accuracy of an FDA-approved blood test that can be used at outpatient memory clinics to diagnose the disease in patients with a range of cognitive impairment. 

"Every patient who walks into my clinic carries a unique story shaped by the brain's complexity," says David T. Jones, M.D., a Mayo Clinic neurologist. "That complexity drew me to neurology and continues to drive my commitment to clearer answers."

8. Mayo Clinic research improves dense breast cancer screening and early detection

Nearly half of all women in the U.S. have dense breast tissue, which can make detecting breast cancer difficult with a mammogram. Mayo Clinic researchers found that adding another test, called molecular breast imaging, or MBI, to a 3D mammogram, improved the ability to find cancer in dense tissue by more than double. 
 
"Our research focuses on detecting the most lethal cancers, which can include invasive tumors that grow quickly. If these are detected earlier, we likely can save more lives," says Carrie Hruska, Ph.D., a Mayo Clinic professor of medical physics and lead author of the study. 

9. Mayo Clinic researchers find 'sugar coating' cells can protect those typically destroyed in type 1 diabetes

After identifying a sugar molecule that cancer cells use on their surfaces to hide from the immune system, Mayo Clinic researchers have found the same molecule may eventually help in the treatment of type 1 diabetes, once known as juvenile diabetes. 

"A goal would be to provide transplantable cells without the need for immunosuppression," says Virginia Shapiro, Ph.D., a Mayo Clinic immunology researcher. "Though we're still in the early stages, this study may be one step toward improving care."

10. New study calculates autoimmune disease prevalence

Mayo Clinic researchers and collaborators have described — for the first time — the prevalence of autoimmune diseases in the U.S. Their research reports that about 15 million people are estimated to have one or more of 105 autoimmune diseases. The study also found that autoimmune diseases occur most often in women, and it identified the top autoimmune diseases by prevalence, sex and age. 
 
"Knowing the number of patients with an autoimmune disease in the U.S. is critical to assess whether these diseases are increasing or decreasing over time and with treatment," says DeLisa Fairweather, Ph.D., vice-chair of translational research for the Department of Cardiovascular Medicine at Mayo Clinic in Florida and corresponding author of the study.

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About Mayo Clinic 
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news. 

Media contact: 

• Julie Ferris-Tillman, Ph.D., Mayo Clinic Communications, newsbureau@mayo.edu

The post A Year of Discovery: 10 Mayo Clinic research breakthroughs moving medicine forward  appeared first on Mayo Clinic News Network.

JACKSONVILLE, Fla. — A new multicenter study led by Mayo Clinic researchers has established a practical, evidence-based definition for rapidly progressive dementia (RPD), a rare but devastating form of cognitive decline that develops over months instead of years. The findings, published in Neurology, the medical journal of the American Academy of Neurology, may help clinicians recognize and treat RPD earlier, and enable researchers to work from a shared framework when studying the condition.

While most types of dementia progress gradually, RPD advances with alarming speed, often leading to significant cognitive decline or death within one to two years. Although it accounts for around 4% of dementia cases, RPD is difficult to diagnose. Symptoms can stem from numerous causes, including autoimmune disease, infections, neurodegenerative disorders such as Alzheimer's disease and rare conditions like Creutzfeldt-Jakob disease. This makes it challenging to consistently define the disorder across different settings.

"Clinicians need a clear, standardized way to identify patients whose decline is unusually fast," says Gregg Day, M.D., a behavioral neurologist at Mayo Clinic and senior author of the study. "This helps ensure that those with potentially treatable causes are recognized quickly, wherever they are seen. Furthermore, this is a necessary step before launching multicenter studies aimed at understanding why a small subset of dementia patients progresses rapidly and how to address this through clinical trials and treatments."

The new definition proposed by Dr. Day and his colleagues uses the Clinical Dementia Rating (CDR) scale, a well-established tool for assessing dementia severity. Criteria are based on the level of functional impairment involving memory, orientation, judgment, problem-solving, community affairs, home and hobbies, and personal care. Under the new framework, a person is considered to have rapidly progressive dementia if they develop mild dementia (CDR score of 1 or higher) within one year of symptom onset, or moderate-to-severe dementia (CDR score of 2 or higher) within two years. Researchers refer to this as the "1-in-1 or 2-in-2" rule.

To test this definition, the research team applied it to two large datasets. The first, known as the RaPID cohort, included 248 patients evaluated for suspected RPD at Mayo Clinic in Florida and Washington University in St. Louis. The second used data from the National Alzheimer's Coordinating Center, representing more than 19,000 participants across 46 research centers in the United States.

In the RaPID group, about 75% of patients met the new criteria. Nearly 1 in 3 had autoimmune or inflammatory causes — many of which are potentially reversible. In the broader national dataset, about 4% met the definition for RPD, with Alzheimer's disease being the most common underlying cause. Across both groups, people who met the RPD definition declined 3 to 4 times faster than those with typical dementia, based on changes measured using the CDR scale.

The new definition proved reliable across clinical and research settings, identifying both rare and common causes of RPD. It can be applied using a patient's clinical history instead of specialized testing, making it adaptable in diverse healthcare settings, including those with limited medical resources.

"By uniformly defining rapid progression, we can better identify patients who might benefit from treatment, improve consistency in research, and ultimately enhance care for people facing one of the most challenging forms of dementia," Dr. Day says.

For a complete list of authors, disclosures and funding, see the paper.

Related:

• Mayo Clinic researchers to study causes of rapidly progressive dementia
• Researchers identify new criteria to detect rapidly progressive dementia

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu

The post New Mayo-led study establishes practical definition for rapidly progressive dementia appeared first on Mayo Clinic News Network.

Early in his medical training, Sarosh Irani, B.M., B.Ch., D.Phil., met a patient who would change the course of his career. The woman, in her mid-30s, arrived at the hospital confused, trembling and wracked by seizures. She was losing her memory and her ability to walk. Yet unlike many with such severe neurological decline, she recovered completely.

Her turnaround came after the clinical team discovered a particular antibody in her blood — proof that her immune system had attacked her brain. When they suppressed that immune response, her symptoms disappeared. The discovery not only changed that woman's life but also opened a window into a new, potentially reversible, facet of medicine — one in which the immune system itself could explain devastating brain diseases.

That revelation propelled Dr. Irani into a field that bridges neurology and immunology, one that continues to expand today from his laboratory at Mayo Clinic in Florida.

A burgeoning field

Dr. Irani's first passion was psychiatry. "I wanted to understand disorders of the mind," he recalls. But he found that the field lacked the molecular footholds that could make its mysteries scientifically tractable. “You couldn't put your hands on the biology,” he says. "There were too many inferences and not enough mechanisms."

He turned to neurology just as scientists were discovering that neurological conditions could, in fact, be autoimmune diseases.

Dr. Irani joined, and subsequently led, the University of Oxford's autoimmune neurology lab, where he helped identify several antibodies that define distinct syndromes — including the antibodies LGI1 and CASPR2, now standard diagnostic markers for treatable forms of various autoimmune neurological conditions.

"What was once a medical curiosity has become a thriving field," says Dr. Irani, who came to Mayo Clinic in 2023. "Twenty years ago, there were no known antibodies affecting the brain. Now we know 20 or 30 such antibodies, and each one represents a potential cure."

Toward Precure

For Irani, these discoveries connect directly to Mayo Clinic's Precure initiative, which aims to predict and prevent disease before symptoms appear. "There are very few examples in medicine where we have a tractable handle on what's causing the disease," he explains. "Here we know the antibodies cause the disease. So the question is simple: How and why are they made? If we can work out causation, we can get close to pre-cure."

His lab is tackling that question through two complementary approaches: exploring patients' genetic predispositions and studying their immune cells. One variant, for example — in an HLA gene involved in presenting proteins to the immune system — appears in more than 90 percent of patients with a particular autoimmune neurological condition.

But genes alone do not tell the whole story. Irani suspects that environmental triggers, such as infections or even medications, act as the final push. "It's likely a multi-hit process," he says. "You need the gene, a misbehaving immune cell and an environmental spark."

His lab is studying patients' own immune cells to trace where this autoimmune process begins. Evidence increasingly points to the periphery, not the brain, as the starting point. That idea is supported by emerging research on the brain's lymphatic drainage system, which helps clear waste and immune molecules.

Early clues to autoimmunity

Recently, Dr. Irani and colleagues showed that biomarkers of neurodegeneration can be detected in the lymph nodes of the neck. These lymph nodes drain byproducts and proteins resulting from brain activity via a network of tiny lymphatic vessels.

Using ultrasound-guided fine-needle aspiration — a quick sampling technique similar to drawing blood — the team measured several proteins including amyloid beta and tau, proteins that build up in Alzheimer's disease, as well as other markers of brain cell health. They found that almost all of these proteins were found in much higher quantities in the lymph nodes than in the blood, especially one called phosphorylated tau (pTau181), which was 266 times more concentrated.

Strikingly, pTau181 levels in lymph nodes decreased with age, suggesting that the brain's ability to clear toxic proteins through lymphatic drainage declines over time — potentially contributing to diseases like Alzheimer's. The discovery also challenges one of medicine's oldest assumptions: that the brain is "immune-privileged" and largely sealed off from the body's immune system.

"This is the first direct evidence that brain proteins accumulate in cervical lymph nodes in living people," says Dr. Irani. "It opens up a minimally invasive way to study how the brain clears waste — and how that process falters with age."

Lymph node aspiration is far less invasive than spinal taps, yet it could offer powerful insight into brain health, aging, and disease progression.

Brain on fire

Dr. Irani's research has come full circle with a new study in The Lancet Psychiatry. The research focuses on patients with autoimmune encephalitis — a condition popularized by the book and movie "Brain on Fire"— whose illnesses often first appear to be psychiatric. The work shows that these patients can be distinguished from others by a simple scoring system based on how rapidly symptoms appear and how they evolve.

"It's a mixture of symptoms — depression, anxiety, psychosis, sleep and eating disturbances — all unfolding over days," he says. "If clinicians recognize that pattern early, we can treat it before irreversible brain injury occurs."

Current therapies for autoimmune encephalitis rely on broad immunosuppression — powerful drugs that quiet the entire immune system and leave patients vulnerable to infection. Dr. Irani envisions a more refined approach that involves the selective silencing of only the harmful immune cells while preserving the rest.

"We want to pick off just the bits causing trouble," he says. "If we can identify exactly what the immune system is attacking, we can teach it tolerance only to that target."

That vision, he believes, could extend to other conditions where the immune system plays a role, potentially informing treatments for dementia, cancer and even common psychiatric disorders. "We're trying to translate these observations to more widespread diseases," he says. "There's enormous potential."

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ROCHESTER, Minn. — Mayo Clinic researchers have developed and tested a new 3D surface scanning approach that gives neurosurgeons even greater precision when operating deep inside the brain.  

The system aligns a patient's head, facial features and surgical head frame with brain images, achieving sub-millimeter accuracy — a level of precision that can make a critical difference in delicate procedures. 

In a feasibility study published in the Journal of Neurosurgery, the 3D scanning method proved more accurate than the CT scan typically used during neurosurgery, all while eliminating exposure to radiation.  

Researchers say the approach could make complex procedures, such as deep brain stimulation, drainage and biopsies safer and more efficient, while enhancing patient comfort. Because it integrates with most surgical navigation systems, it may also bring high-precision guidance to operating rooms that don't have a CT scanner. 

How the new 3D approach works 

Using cameras and structured-light scanning, the new system creates high-resolution 3D models of the patient's face and the surgical frame that keeps the head still. It merges these images into a detailed spatial “map” of the patient's position in the operating room. That map is then matched with pre-surgery brain scans, such as MRI or CT images, giving surgeons precise, real-time guidance to reach the exact target in the brain.  

In the study, the system's computer analysis aligned images with an average precision of 0.14 millimeters — compared with about 0.20 millimeters typically achieved with CT scans. The difference is roughly the width of a pencil tip, but in delicate brain surgery, that fraction can be enough to affect accuracy. 

Teamwork behind the breakthrough 

The project combined Mayo Clinic's engineering and surgical expertise. Jaeyun Sung, Ph.D., a Mayo Clinic computational biologist, clinical AI researcher and corresponding author, led the engineering and computational work. Dr. Sung focuses on using engineering and computer science to develop advanced precision medicine tools for patient care.  

"When engineers and neurosurgeons look at the same challenge, we see different details, and that's where breakthroughs can happen," Dr. Sung says. "This is about building the next generation of surgical tools that bring engineering-level, sub-millimeter precision directly into the operating room." 

Kendall Lee, M.D., Ph.D., a Mayo Clinic neurosurgeon, led the surgical integration of the technology and said it could make a real difference for patients and improve his practice.  

"Some of the most important steps in neurosurgery happen before we even begin the operation," Dr. Lee says. "This new 3D scanning method is safe, quick and cost-effective, and it can help us hit the right target more accurately, improving how we care for patients."  

Basel Sharaf, M.D., D.D.S., a Mayo Clinic surgeon and lead author of the study, sees even greater possibilities ahead for the technology.  

"In the future, 3D surface scanning could be as simple as using a smartphone," Dr. Sharaf says. "With advanced AI, the system could adapt in real time, even predicting small shifts in the brain to help surgeons work with greater accuracy and a smoother workflow."  

Next Steps: Advancing automation, AI and clinical validation

The team is now working to add automation and artificial intelligence to help make the process faster and easier to use. They are also testing new hardware and running a larger clinical trial to further evaluate the technique's effectiveness in brain surgery.  

Review the study for a complete list of authors, disclosures and funding.

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About Mayo Clinic
Mayo Clinic is a nonprofit organization committed to innovation in clinical practice, education and research, and providing compassion, expertise and answers to everyone who needs healing. Visit the Mayo Clinic News Network for additional Mayo Clinic news.

Media contact:

• Tia Ford, Mayo Clinic Communications, newsbureau@mayo.edu 

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