Tag: 2/6/25

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Brain Stimulation and Mindfulness Exercises Could Reduce ‘Latchkey Incontinence’

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Urinary incontinence. Credit: Scientific Animations CC4.0

Arriving home after a long day may be a relief, but for some people, seeing their front door or inserting a key into the lock triggers a powerful urge to pee. Known as “latchkey incontinence,” this phenomenon is the subject of a new study by researchers at the University of Pittsburgh who found that mindfulness training and/or non-invasive brain stimulation could reduce bladder leaks and feelings of urgency evoked by these cues. 

The findings of the pilot study, the first evaluation of brain-based therapies for urinary incontinence, are published in the latest issue of the journal Continence. 

“Incontinence is a massive deal,” said senior author Dr. Becky Clarkson, research assistant professor in the Pitt School of Medicine Division of Geriatrics and co-director of the Continence Research Center. “Bladder leaks can be really traumatizing. People often feel like they can’t go out and socialise or exercise because they’re worried about having an accident. Especially for older adults, this feeds into social isolation, depression and functional decline. Our research aims to empower people with tools to get back their quality of life.” 

Latchkey incontinence, or situational urgency urinary incontinence, is bladder leakage triggered by specific environments or scenarios. Common cues include one’s front or garage door, running water, getting into a car or walking past public restrooms. 

According to lead author Dr. Cynthia Conklin, associate professor in the Pitt Department of Psychiatry, latchkey incontinence is a type of Pavlovian conditioning. Like Pavlov’s dogs, which salivated upon hearing a bell that they associated with food, years of going to the bathroom immediately upon entering the house can condition one to feel strong bladder urgency when seeing the front door.

In a previous study, Clarkson and Conklin showed participants pictures of their own front doors or other triggers versus “safe” images of things that did not evoke urgency while they had an MRI of their brain. A part of the brain called the dorsolateral prefrontal cortex was more active when participants viewed urgency-related images.  

“The prefrontal cortex is the seat of cognitive control,” said Clarkson. “It’s the executive function center of the bladder, the bit that is telling you, ‘Okay, it’s time to go. You should find somewhere to go.’” 

The researchers hypothesised that activating this part of the brain during exposure to urgency cues, through mindfulness and/or with transcranial direct current stimulation (tDCS) of the brain, could improve participants’ ability to regulate responses to these cues and control urgency and leakage.  

They recruited 61 women aged over 40 who reported regular situationally triggered bladder leaks and randomly assigned them to one of three groups: Participants either listened to a 20-minute mindfulness exercise, received tDCS or both while viewing personal trigger photos.  

The mindfulness exercise, developed by coauthor Dr Carol Greco, associate professor of psychiatry and physical therapy at Pitt, was like a typical body scan practice that instructs participants to move through their body, bringing attention to each part in turn. But unlike most body scans, it included specific acknowledgment of bladder sensation.  

After completing four in-office sessions over five to six days, participants in all three groups experienced reduced urgency when they viewed trigger cues. Women in all three groups also reported an improvement in the number of urgency episodes and leaks after completing the sessions. 

Although this pilot study did not have a control group, for comparison, the researchers say that the magnitude of improvement from tDCS and mindfulness was similar to what other research has reported for interventions such as medications and pelvic floor therapy.  

“Although we need to do more research, these results are really encouraging because they suggest that a behavioral tool like mindfulness can be an alternative or additional way to improve symptoms,” said Conklin. “Balancing multiple prescriptions is a big issue among older adults, and a lot of people are reluctant to take another medication, so I think that’s one of the reasons that we saw such high acceptability of non-pharmacologic interventions in this study.” 

More than 90% of recruited participants completed the study.  

“Participants loved it,” said Clarkson. “Almost everyone who started the study finished it, even though coming into the office four days within one week was quite a big commitment. We got really great feedback, and a lot of women told us that they continue to use the mindfulness exercise in their daily lives.” 

“For the first time in 20 years of doing research, we got thank you cards!” added Conklin. “I think that incontinence is such a taboo subject, and a lot of people find it difficult to talk about, so they often don’t even realize that there are treatments out there. But you don’t have to suffer in silence.” 

Now, the researchers are planning to explore whether the mindfulness component of the study could be helpful in independent living facilities to reach a wide range of older adults. They also hope to eventually develop an app-based tool for smartphones. 

Source: University of Pittsburgh

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Common Gene Variant Doubles Dementia Risk for Men

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New research has found that men who carry a common genetic variant are twice as likely to develop dementia in their lifetime compared to women. The research, published in Neurology, used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether people who had variants in the haemochromatosis (HFE) gene, which is critical for regulating iron levels in the body, might be at increased risk of dementia.

Co-author Professor John Olynyk, from the Curtin Medical School, said one in three people carry one copy of the variant, known as H63D, while one in 36 carry two copies.

“Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women,” Professor Olynyk said.

“While the genetic variant itself cannot be changed, the brain pathways which it affects – leading to the damage that causes dementia – could potentially be treated if we understood more about it.”

Professor Olynyk said further research was needed to investigate why this genetic variant increased the risk of dementia for males but not females.

“The HFE gene is routinely tested for in most Western countries including Australia when assessing people for haemochromatosis – a disorder that causes the body to absorb too much iron. Our findings suggest that perhaps this testing could be offered to men more broadly,” Professor Olynyk said.

“While the HFE gene is critical for controlling iron levels in the body, we found no direct link between iron levels in the blood and increased dementia risk in affected men.

“This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body.”

The ASPREE trial was a double-blind, randomised, placebo-controlled trial of daily low-aspirin in 19 114 healthy older people in Australia and the USA. Primarily undertaken to evaluate the risks versus benefits of daily low-dose aspirin in this cohort, it created a treasure trove of healthy ageing data that has underpinned a wealth of research studies.

Source: Curtin University

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Could ‘Pausing’ Necrosis be the Final Frontier in Ageing and Medicine?

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Necrosis, unprogrammed cell death, spews a host of toxic molecules into the cellular environment. Credit: University College London

In a new study, published in Oncogene, a world-leading international team of scientists and clinicians explore the potential of necrosis to reshape our understanding and treatment of age-related conditions and even protect astronauts on longer journeys into space.

Challenging prevailing views, the paper brings together evidence from cancer biology, regenerative medicine, kidney disease, and space health to argue that necrosis is not merely an endpoint, but a key driver of aging that presents an opportunity for intervention.

Dr Keith Siew, an author of the study from UCL Centre for Kidney & Bladder Health, said: “Nobody really likes talking about death, even cell death, which is perhaps why the physiology of death is so poorly understood. And in a way necrosis is death. If enough cells die, then tissues die, then we die. The question is what would happen if we could pause or stop necrosis.”

Dr Carina Kern, lead author of the study and CEO of LinkGevity, a biotech company based at Cambridge’s Babraham Research Campus and part of the NASA Space-Health program, said: “Necrosis remains one of the last frontiers in medicine – a common thread across aging, disease, space biology, and scientific progress itself.”

Cells are the fundamental building blocks of life and can die in various ways. ‘Programmed’ forms of cell death are beneficial, carefully orchestrated processes that allow our tissues to replenish themselves and function well throughout life.

But ‘unprogrammed’ cell death, or necrosis, is an uncontrolled and catastrophic process that leads to tissue degeneration and biological decline.

At the centre of the necrotic process is calcium, a vital resource that effectively controls the cell by determining which functions are switched on or off. Calcium ions are normally maintained at a level that is 10 000 to 100 000 times higher outside the cell than inside.

When this finely tuned balance fails, calcium floods the cell like an electrical short circuit, pushing the cell into chaos. Unlike programmed death, where cells dismantle in an orderly manner, necrosis causes cells to rupture, spilling toxic molecules into surrounding tissues.

This sparks a chain reaction that causes widespread inflammation and affects tissue repair, creating a snowball effect that ultimately leads to frailty and the onset of chronic age-related conditions such as kidney disease, heart disease and Alzheimer’s.

Dr Siew added: “When cells die, it’s not always a peaceful process for the neighbours.”

Dr Kern explains: “Necrosis has been hiding in plain sight. As a final stage of cell death, it’s been largely overlooked. But mounting evidence shows it’s far more than an endpoint. It’s a central mechanism through which systemic degeneration not only arises but also spreads. That makes it a critical point of convergence across many diseases. If we can target necrosis, we could unlock entirely new ways to treat conditions ranging from kidney failure to cardiac disease, neurodegeneration, and even aging itself.”

Notably, it is in the kidneys that necrosis may have its most devastating and underappreciated impact. Necrosis induces kidney disease, which can lead to kidney failure requiring a transplant or dialysis. By age 75 nearly half of all individuals develop some degree of kidney disease as part of the natural aging process.

Dr Siew added: “With kidney disease, there’s no one underlying reason that the kidneys fail. It could be a lack of oxygen, inflammation, oxidative stress, a build-up of toxins, and so on. All of these stressors eventually lead to necrosis, which initiates a positive feedback loop that spirals out of control, leading to kidney failure. We can’t stop all of these stressors, but if you could intervene at the point of necrosis, you’d effectively achieve the same result.”

Another area where interrupting necrosis could have a big impact is spaceflight, where astronauts often experience accelerated ageing and kidney-related decline due to the effects of low gravity and exposure to cosmic radiation. A 2024 study involving Dr Siew demonstrated that the human kidney may be the ultimate bottleneck for long-duration space missions.

The authors say finding solutions to this accelerated aging and kidney disease may be the final frontier for human deep space exploration.

Dr Kern said: “In many age-related diseases – affecting diverse organs such as the lungs, kidneys, liver, brain, and cardiovascular system – relentless cascades of necrosis fuel the progression of disease. This is often alongside impaired healing that leads to fibrosis, inflammation and damaged cells. Each cascade triggers and amplifies the next.

“If we could prevent necrosis, even temporarily, we would be shutting down these destructive cycles at their source, enabling normal physiological processes and cell division to resume – and potentially even allowing for regeneration.”

Source: University College London

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What Does Caffeine Do to the Sleeping Brain?

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Photo by Mike Kenneally on Unsplash

Caffeine is one of the most widely consumed psychoactive substances in the world, present in tea, coffee, chocolate and energy drinks. In a study published in Nature Communications Biology, a team of researchers from Université de Montréal shed new light on how caffeine can modify sleep and influence the brain’s recovery, both physical and cognitive, overnight.

The research was led by Philipp Thölke, a research trainee at UdeM’s Cognitive and Computational Neuroscience Laboratory (CoCo Lab), and co-led by the lab’s director Karim Jerbi, a psychology professor and researcher at Mila – Quebec AI Institute.

Working with sleep-and-aging psychology professor Julie Carrier and her team at UdeM’s Centre for Advanced Research in Sleep Medicine, the scientists used AI and electroencephalography (EEG) to study caffeine’s effect on sleep.

They showed for the first time that caffeine increases the complexity of brain signals and enhances brain “criticality” during sleep.  Interestingly, this was more pronounced in younger adults.

“Criticality describes a state of the brain that is balanced between order and chaos,” said Jerbi.

“It’s like an orchestra: too quiet and nothing happens, too chaotic and there’s cacophony. Criticality is the happy medium where brain activity is both organised and flexible. In this state, the brain functions optimally: it can process information efficiently, adapt quickly, learn and make decisions with agility.”

Added Carrier: “Caffeine stimulates the brain and pushes it into a state of criticality, where it is more awake, alert and reactive. While this is useful during the day for concentration, this state could interfere with rest at night: the brain would neither relax nor recover properly.”

Nocturnal brain activity

To study how caffeine affects the sleeping brain, Carrier’s team recorded the nocturnal brain activity of 40 healthy adults using an electroencephalogram.  They compared each participant’s brain activity on two separate nights, one when they consumed caffeine capsules three hours and then one hour before bedtime, and another when they took a placebo at the same times.

“We used advanced statistical analysis and artificial intelligence to identify subtle changes in neuronal activity,” said Thölke, the study’s first author. “The results showed that caffeine increased the complexity of brain signals, reflecting more dynamic and less predictable neuronal activity, especially during the non-rapid eye movement (NREM) phase of sleep that’s crucial for memory consolidation and cognitive recovery.”

The researchers also discovered striking changes in the brain’s electrical rhythms during sleep: caffeine attenuated slower oscillations such as theta and alpha waves (generally associated with deep, restorative sleep) and stimulated beta wave activity, which is more common during wakefulness and mental engagement.

“These changes suggest that even during sleep, the brain remains in a more activated, less restorative state under the influence of caffeine,” says Jerbi, who also holds the Canada Research Chair in Computational Neuroscience and Cognitive Neuroimaging. “This change in the brain’s rhythmic activity may help explain why caffeine affects the efficiency with which the brain recovers during the night, with potential consequences for memory processing.”

People in their 20s more affected

The study also showed that the effects of caffeine on brain dynamics were significantly more pronounced in young adults between ages 20 and 27 compared to middle-aged participants aged 41 to 58, especially during REM sleep, the phase associated with dreaming.

Young adults showed a greater response to caffeine, likely due to a higher density of adenosine receptors in their brains. Adenosine is a molecule that gradually accumulates in the brain throughout the day, causing a feeling of fatigue.

“Adenosine receptors naturally decrease with age, reducing caffeine’s ability to block them and improve brain complexity, which may partly explain the reduced effect of caffeine observed in middle-aged participants,” Carrier said.

And these age-related differences suggest that younger brains may be more susceptible to the stimulant effects of caffeine. Given caffeine’s widespread use, the researchers stress the importance of understanding its complex effects on brain activity across different age groups and health conditions.

They add that further research is needed to clarify how these neural changes affect cognitive health and daily functioning, and to potentially guide personalised recommendations for caffeine intake.

Source: University of Montreal

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Pilot IBS Study Suggests Mediterranean Diet May be an Alternative to Low FODMAP

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A pilot study from Michigan Medicine researchers found that the Mediterranean diet may provide symptom relief for people with irritable bowel syndrome. For the study, which was published in Neurogastroenterology & Motility, participants were randomised into two groups, one following the Mediterranean diet and the other following the low FODMAP diet, a common restrictive diet for IBS.

In the Mediterranean diet group, 73% of the patients met the primary endpoint for symptom improvement, versus 81.8% in the low FODMAP group.

Irritable bowel syndrome affects an estimated 4-11% of all people, and a majority of patients prefer dietary interventions to medication. The low FODMAP diet leads to symptom improvement in more than half of patients, but is restrictive and hard to follow.

Previous investigations from Michigan Medicine researchers into more accessible alternative diets led to a proposed “FODMAP simple,” which attempted to only restrict the food groups in the FODMAP acronym that are most likely to cause symptoms.

“Restrictive diets, such as low FODMAP, can be difficult for patients to adopt,” said Prashant Singh, MBBS, Michigan Medicine gastroenterologist and lead author on the paper.

“In addition to the issue of being costly and time-consuming, there are concerns about nutrient deficiencies and disordered eating when trying a low FODMAP diet. The Mediterranean diet interested us as an alternative that is not an elimination diet and overcomes several of these limitations related to a low FODMAP diet.”

The Mediterranean diet is already popular among physicians for its benefits to cardiovascular, cognitive, and general health. Previous research on the effect of the Mediterranean diet on IBS, however, had yielded conflicting results.

In this pilot study, two groups of patients, diagnosed with either IBS-D (diarrhoea) or IBS-M (mixed symptoms of constipation or diarrhoea), were provided with either a Mediterranean diet or the restriction phase of a low FODMAP diet for four weeks.

The primary endpoint was an FDA-standard 30% reduction in abdominal pain intensity after four weeks.

This study was the first randomised controlled trial to compare the Mediterranean diet to another potential diet. While the Mediterranean diet did provide symptom relief, the low FODMAP group experienced a greater improvement measured by both abdominal pain intensity and IBS symptom severity score.

Researchers found the results of this pilot study, which 20 patients completed, sufficiently encouraging to warrant future, larger controlled trials to investigate the potential of the Mediterranean diet as an effective intervention for patients with IBS.

“This study adds to a growing body of evidence which suggests that a Mediterranean diet might be a useful addition to the menu of evidence-based dietary interventions for patients with IBS,” said William Chey, MD, chief of Gastroenterology at the University of Michigan, president-elect of the American College of Gastroenterology, and senior author on the paper.

The researchers believe studies comparing long-term efficacy of the Mediterranean diet with long-term outcomes following the reintroduction and personalisation phases of low FODMAP are needed.

Source: Michigan Medicine – University of Michigan