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A Key ‘Youth Molecule’ May Hold the Secret to Enhancing Wellbeing in Older Adults – Evidence from Multiple Clinical Studies

Scientists from the University of Oslo (UiO), Akershus University Hospital (Ahus), and a network of international collaborators have published a compelling expert opinion in Nature Aging. This significant contribution unites over twenty-five leading researchers from around the world, encompassing clinicians, metabolic scientists, and renowned authorities in the field of ageing biology. Together, they present a comprehensive perspective on nicotinamide adenine dinucleotide (NAD⁺), a molecule that is emerging as a central player in maintaining cellular health. Their collective insight highlights an expanding international commitment to uncovering how this minute but vital compound could hold the key to promoting healthier ageing and protecting against debilitating neurodegenerative diseases such as Alzheimer’s and Parkinson’s.

Often described as a cell’s “fuel regulator,” NAD⁺ performs a wide array of crucial biological functions. It supports the body’s ability to generate energy, facilitates the repair of damaged DNA, and helps sustain normal cellular operations. However, as humans age, NAD⁺ levels naturally diminish—a decline increasingly associated with impaired memory, muscle weakness, fatigue, and the development of several age-related disorders. As Dr Jianying Zhang, one of the paper’s lead authors, explains, “Fine-tuning NAD⁺ metabolism holds promise for delaying age-related health decline as well as diseases associated with premature ageing. Yet, to truly unlock its therapeutic potential, we must deepen our understanding of appropriate dosing, long-term safety, and individual variability in response to NAD⁺ augmentation strategies.” Zhang’s remarks encapsulate a growing consensus within the scientific community that while NAD⁺ offers extraordinary potential, much remains to be explored before it can be effectively translated into clinical practice.

The expert opinion synthesises years of research, integrating findings from numerous preclinical and clinical studies investigating ways to elevate NAD⁺ levels. Most notably, these efforts have centred on the administration of vitamin B3-related precursors such as nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Early experimental outcomes have been promising, with some human trials suggesting improvements in cognitive performance, motor coordination, and metabolic efficiency. Nonetheless, the researchers emphasise the need for larger-scale and long-term clinical studies to confirm these preliminary observations. Only through such rigorous and sustained investigation, they argue, can the true therapeutic potential of NAD⁺ enhancement be accurately assessed across a spectrum of diseases and physiological conditions.

The publication arrives at an especially opportune moment, as both scientific and public interest in NAD⁺ biology have reached unprecedented levels. Around the world, including in Norway, numerous clinical trials are currently underway to evaluate the safety and efficacy of NAD⁺ precursors, such as NR and NMN. These compounds have simultaneously gained considerable commercial traction, forming part of a rapidly expanding market for so-called “longevity supplements.” Yet this surge in popularity has also given rise to significant debate regarding the relative effectiveness of different NAD⁺ boosters and the reliability of claims made by supplement manufacturers. In this context, the Nature Aging article offers not merely scientific analysis but also much-needed clarity amid the surrounding uncertainty and speculation.

“This is precisely why we believe the timing is right for an expert perspective,” remarks Dr Evandro Fei Fang-Stavem, senior author of the article and head of the Fang Lab at UiO and Ahus. “NAD⁺ is essential for life itself, but there remains a great deal of confusion and misinformation about how best to use NAD⁺-related supplements and therapies. Our work consolidates the available evidence, delineates current gaps in knowledge, and provides a roadmap to guide future research and clinical applications.” Dr Fang-Stavem’s statement reflects the article’s broader ambition: to steer both researchers and clinicians towards a more coordinated and scientifically grounded understanding of NAD⁺ biology, while cautioning against premature assumptions driven by hype rather than evidence.

The sentiment is echoed by Professor Torbjørn Omland, MD, PhD, MPH, Deputy Head of the Institute of Clinical Medicine and co-author of the paper, who notes that the review provides a vital bridge between basic researchers and clinicians. “There is a clear knowledge gap regarding NAD⁺ and its clinical implications,” he observes. “This paper delivers the latest expert guidance for those investigating NAD⁺ biology and will serve as a valuable resource for the numerous NAD⁺-related clinical trials currently underway. These studies span an impressive range of conditions, from neurological and cardiovascular diseases to general age-related decline.” In essence, the review functions as both a scholarly synthesis and a practical reference for a field that is rapidly evolving but still in need of unifying principles and robust data.

Ultimately, the authors call for continued international collaboration, larger and more diverse participant pools, and stringent methodological standards to ensure that the promising science of NAD⁺ can be translated into tangible medical progress. They emphasise that while the enthusiasm surrounding NAD⁺ supplementation is understandable—given its role in cellular energy and repair—the field must proceed with careful scientific scrutiny rather than commercial enthusiasm. The promise of NAD⁺ lies not only in its biochemical properties but also in the research community’s ability to harmonise its understanding of how, when, and for whom NAD⁺ therapies can be most beneficial. With this Nature Aging publication, the University of Oslo, Ahus, and their global partners have made a crucial contribution to that collective effort—laying the foundation for a future in which the biology of ageing can be harnessed to improve both lifespan and healthspan for generations to come.

More information: Jianying Zhang et al, Emerging strategies, applications and challenges of targeting NAD+ in the clinic, Nature Aging. DOI: 10.1038/s43587-025-00947-6

Journal information: Nature Aging Provided by University of Oslo, Ullevaal University Hospital

Alarming rise in memory and thinking difficulties found in American population

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A recent study, published on September 24, 2025, in Neurology®, the medical journal of the American Academy of Neurology, has revealed a troubling rise in self-reported cognitive problems among adults in the United States. The findings indicate that an increasing number of people—particularly those under the age of forty—are experiencing severe difficulties with memory, concentration, and decision-making. This large-scale study, which analysed over 4.5 million survey responses collected annually between 2013 and 2023, suggests that cognitive challenges are not confined to older populations, as is often assumed, but are spreading more rapidly among younger generations. The data point to a concerning public health trend that may reflect not only biological or lifestyle changes but also deep social and economic inequalities influencing brain health in modern America.

Dr Adam de Havenon, MD, MS, of Yale School of Medicine and a Fellow of the American Academy of Neurology, led the research and described the findings as an emerging national health issue. “Challenges with memory and thinking have emerged as a leading health issue reported by U.S. adults,” he stated. “Our study shows that these difficulties may be becoming more widespread, especially among younger adults, and that social and structural factors likely play a key role.” His remarks highlight the dual dimensions of this problem: while some of the increase may stem from genuine shifts in neurological health, much of it appears to be intertwined with the pressures and inequities of modern living. Stress, economic hardship, inadequate health care, and educational disparities all seem to converge in ways that affect mental and cognitive functioning across the population.

The research drew on data from the Behavioural Risk Factor Surveillance System, a long-running annual survey conducted across the United States. Respondents were asked whether, because of a physical, mental, or emotional condition, they had serious difficulty concentrating, remembering, or making decisions. Those who answered “yes” were classified as having a cognitive disability. The researchers deliberately excluded data from 2020, when the COVID-19 pandemic profoundly altered patterns of mental and physical health, as well as responses from individuals reporting depression, to avoid overlapping psychological factors. Even with these exclusions, the results demonstrated a striking rise in reported difficulties. From 2013 to 2023, the national rate of cognitive disability increased from 5.3% to 7.4%, with the first noticeable uptick occurring in 2016.

Younger adults were the group most affected by this change. For people under forty, the rate of reported cognitive disability nearly doubled, climbing from 5.1% in 2013 to 9.7% in 2023. In contrast, rates among adults aged seventy and older declined slightly, from 7.3% to 6.6%. This generational divide is particularly noteworthy, as it suggests that factors unique to younger adults—such as increased stress from financial instability, digital overstimulation, long working hours, and sleep deprivation—could be influencing cognitive function. Dr de Havenon cautioned that while the survey does not directly measure clinical impairment, the rising prevalence of self-reported memory and concentration problems among younger adults signals an urgent need to investigate environmental, behavioural, and societal contributors to cognitive decline.

The study also exposed deep socioeconomic and educational disparities in cognitive health. Adults with household incomes below $35,000 consistently reported the highest rates of difficulty, increasing from 8.8% to 12.6% over the ten years. By contrast, those with incomes exceeding $75,000 had significantly lower rates, although these rates still increased modestly, from 1.8% to 3.9%. Similarly, people without a high school diploma reported a significant rise—from 11.1% to 14.3%—compared with college graduates, whose rates climbed from 2.1% to 3.6%. These findings highlight how economic and educational disadvantage can exacerbate cognitive challenges, possibly through mechanisms such as chronic stress, limited access to health care, poor nutrition, and restricted opportunities for cognitive engagement. The consistent pattern across income and education levels implies that cognitive difficulties are as much a social issue as a medical one.

Racial and ethnic disparities further complicate the picture. Although the majority of survey respondents were white, increases in cognitive disability were observed across nearly every demographic group. American Indian and Alaska Native adults exhibited the highest prevalence, rising from 7.5% to 11.2%, while Hispanic adults saw an increase from 6.8% to 9.9%. Black adults experienced a smaller increase, from 7.3% to 8.2%, whereas white adults rose from 4.5% to 6.3%. Asian adults, though reporting the lowest overall rates, still showed an increase from 3.9% to 4.8%. Dr de Havenon pointed to these disparities as further evidence that structural inequities—such as access to education, health care, and employment—shape not only physical but also cognitive well-being. “We’re seeing the steepest increases in memory and thinking problems among people who already face structural disadvantages,” he said. “We need to understand better and address the underlying social and economic factors that may be driving this trend.”

Despite the scale and robustness of the dataset, the study has limitations. The researchers acknowledged that data were gathered through telephone surveys, meaning responses depended on individuals’ recollections and subjective perceptions of their difficulties. This method introduces potential inaccuracies, as participants might misinterpret the question, overstate their symptoms, or underreport due to stigma. Moreover, the definition of “cognitive disability” was broad, encompassing a wide range of difficulties that might not equate to measurable cognitive impairment. Nevertheless, the consistent upward trend across demographics and income levels gives the findings significant credibility. Dr de Havenon called for more research into the causes of this shift, particularly among younger adults, given its long-term implications for health, productivity, and the health care system. Whether the rise reflects genuine neurological changes, increased awareness, or a greater willingness to report symptoms, the results indicate a real and troubling phenomenon that warrants urgent public health attention.

In conclusion, the study paints a sobering portrait of cognitive health in contemporary America. The data suggest that memory and thinking problems are no longer confined to the elderly but are increasingly affecting younger and economically disadvantaged populations. If these patterns persist, the long-term consequences could be profound, affecting not only the individual’s quality of life but also national productivity and social stability. As the researchers note, urgent interdisciplinary action is required—combining medical, social, and policy-based approaches—to identify the causes of these trends and mitigate their impact. In the meantime, the growing prevalence of self-reported cognitive difficulties among Americans under forty stands as a warning sign: one that demands attention not only from neurologists and psychologists but from society as a whole.

More information: Adam de Havenon et al, Rising Cognitive Disability as a Public Health Concern Among US Adults Trends From the Behavioral Risk Factor Surveillance System, 2013–2023, Neurology. DOI: 10.1212/WNL.0000000000214226

Journal information: Neurology Provided by American Academy of Neurology

Could a daily mango help keep diabetes at bay?

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If you were presented with two snacks—one containing a modest seven grams of sugar and another boasting over thirty—it would seem instinctive to choose the former. Most people have been conditioned to believe that less sugar automatically equates to better health. Yet, nutrition is far more complex than such straightforward arithmetic. Foods do not exist in isolation, and the impact they have on the body depends not only on their sugar content but on the matrix of nutrients, fibres, and bioactive compounds that accompany that sugar. Thus, the assumption that the lower-sugar snack is automatically healthier deserves a more nuanced examination.

For nearly one hundred million adults in the United States living with prediabetes, the idea that a sweet tropical fruit could help reduce the risk of diabetes may sound implausible. Tropical fruits, after all, are known for their naturally high sugar content—often ranging from ten to fifty grams per serving. Mangoes, one of the sweetest of these fruits, frequently find themselves on the “to avoid” list for those watching their blood sugar levels. At first glance, this reasoning seems sensible. However, recent research led by clinical nutrition scientist Raedeh Basiri offers a fascinating counterpoint. Her work suggests that mangoes, despite their natural sweetness, may actually confer metabolic benefits that could help prevent diabetes, particularly in individuals at risk of developing it.

Dr Raedeh Basiri, an assistant professor in George Mason University’s Department of Nutrition and Food Studies, has emphasised the importance of considering foods in their total nutritional context. “It is not just the sugar content that matters, but the overall food context that matters,” she explains. Her team’s study marks a milestone as the first long-term clinical trial to show both metabolic and body composition benefits associated with regular mango consumption in prediabetic adults. These findings challenge the prevailing narrative that foods high in natural sugars are inherently detrimental, and instead highlight the importance of how nutrients interact within whole foods to influence health outcomes.

In essence, it is not merely the amount of sugar that dictates a food’s healthfulness, but the form and context in which that sugar is delivered. Mangoes contain natural sugars that are bound within a fibrous structure and accompanied by beneficial compounds such as vitamins A and C, antioxidants, and phytonutrients. This combination slows sugar absorption, supports gut health, and provides anti-inflammatory effects. In contrast, many processed snacks—particularly those marketed as “low-sugar” or “diabetic-friendly”—lack these natural co-factors. They may contain refined carbohydrates, artificial sweeteners, or additives that disrupt metabolic balance and may even increase the long-term risk of insulin resistance.

Basiri’s objective, as she articulates it, is to encourage a shift in focus towards whole fruits as part of balanced, evidence-based dietary strategies for diabetes prevention. “The goal is to encourage people to include whole fruits, like mango, as part of healthy eating behaviours and practical dietary strategies for diabetes prevention,” she says. “Individuals at high risk of diabetes should not only focus on the sugar content of foods, but on how sugars are delivered.” This distinction between naturally occurring and added sugars is crucial. The sugars in fruits come packaged with nutrients that enhance their digestibility and lessen their metabolic strain. In contrast, added sugars in refined foods are stripped of their nutritional balance and often lead to unhealthy spikes in blood glucose levels.

To investigate these effects in real-world conditions, Basiri and her research team conducted a six-month randomised clinical trial. Participants were divided into two groups: one group consumed a fresh mango daily, while the other received a commercially produced low-sugar granola bar. The researchers closely monitored participants’ blood glucose levels, insulin responses, and changes in body fat composition throughout the study. The comparison between a high-sugar fruit and a low-sugar snack bar offered a clear test of whether natural sugars, in their whole-food context, behave differently in the body from those found in processed foods.

The results were both surprising and illuminating. Despite containing nearly three times as much sugar—approximately 32 grams compared with 11 grams in the granola bar—the mango group exhibited superior health outcomes. Participants who consumed mangoes daily demonstrated improved blood glucose control, enhanced insulin sensitivity, and measurable reductions in body fat. These findings reinforce the idea that whole fruits should not be unfairly demonised for their natural sweetness. Instead, they illustrate that the body responds differently to sugars consumed in their natural form, where fibre and phytonutrients work in harmony to support metabolic health. Basiri’s research thus offers a powerful reminder that nutrition is about balance and biological context rather than mere numbers on a nutritional label. When it comes to managing or preventing diabetes, the key may not lie in shunning sweetness altogether, but in embracing it from the right sources—those that nature has already balanced for us.

More information: Raedeh Basiri et al, Daily Mango Intake Improves Glycemic and Body Composition Outcomes in Adults with Prediabetes: A Randomized Controlled Study, Foods. DOI: 10.3390/foods14172971

Journal information: Foods Provided by George Mason University

Close Ties: Nearly 50% of American Grandchildren Live Near a Grandparent

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New, exact estimates indicate that most American grandchildren reside close to at least one grandparent, a finding that carries important implications for family well-being as well as for how time and resources are shared across generations. Cornell researchers report that nearly half of U.S. grandchildren—about 47 per cent—live within ten miles of a grandparent. Many live even closer: 21 per cent within one to five miles, and 13 per cent within a walkable mile, strikingly, as many grandchildren live within one mile of their grandparents as those who are separated by a distance of 500 miles or more.

The analysis also revealed significant socioeconomic differences between families living near their grandparents and those living farther away from them. Families in closer proximity tend to have parents with lower levels of education and income, and they are less likely to be married. In these households, grandparents and parents exchange greater amounts of help in the form of time and support, though not in financial transfers. Proximity fosters interdependence in care and everyday assistance, but the circulation of money is unaffected by distance.

Rachel Dunifon, the Rebecca Q. and James C. Morgan Dean of the College of Human Ecology at Cornell, emphasised the importance of these findings, noting: “Substantial numbers of grandchildren live very close to a grandparent. Additionally, our results reveal that the characteristics of families living very close to grandparents differ from the characteristics of those living just a little farther away.” Dunifon co-authored the study Grandchildren’s Spatial Proximity to Grandparents and Intergenerational Support in the United States, published in Demographic Research on 3 June, with Olivia Healy, now an assistant professor of economics at Elon University.

Earlier research had typically relied on broader measures, treating “close” proximity as within 25 to 30 miles. This approach, however, overlooked essential distinctions among the many families clustered within much smaller distances. The Cornell study, drawing on nearly 2,000 households from the nationally representative Panel Study of Income Dynamics, used detailed census block-level location data to calculate the precise distances between grandparents and grandchildren. This methodological advance provided a clearer view of the diversity of relationships at the closest range, where slight differences in distance can translate into very different family dynamics.

The researchers found that, as might be expected, families living near one another spend more time together. Yet the intensity of contact was especially pronounced among those within a one-mile radius, far surpassing families only slightly farther apart. These patterns suggest that families who share such proximity are deeply integrated into each other’s lives, and that this embeddedness shapes everyday routines, caregiving practices, and social support. Understanding how and why families arrange themselves in such close quarters, and the consequences for family functioning, represents an important area for future study.

Although some might assume that grandparents who live at greater distances compensate through financial contributions, the evidence showed otherwise. Families living farther away, who also tended to have higher incomes and education, were more self-sufficient and did not receive greater monetary support. Instead, the overall flow of resources still favoured grandchildren’s households, with nearby grandparents providing substantial childcare hours and financial assistance. These findings underscore the impact of proximity on intergenerational exchange and, by extension, the well-being of children, parents, and grandparents alike.

More information: Rachel Dunifon et al, Grandchildren’s spatial proximity to grandparents and intergenerational support in the United States, Demographic Research. DOI: 10.4054/DemRes.2025.52.34

Journal information: Demographic Research Provided by Cornell University

Research links physical activity to lower rates of depression and insomnia in ageing smokers

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Regular weekly exercise may help smokers over the age of 40 lower their risks of depression and sleep disturbances, bringing them closer to the levels seen in non-smokers. This conclusion is based on a study by the Texas A&M University School of Public Health, which investigated the relationship between smoking, physical activity, and mental and sleep health.

The researchers found that smokers generally had higher rates of moderate to severe depressive symptoms and sleep disorders compared with non-smokers. The problem was most evident among adults aged 40 to 59 who did not meet recommended physical activity levels, as they were especially likely to experience poor mental health and disrupted sleep. Among smokers aged 60 and older, sleep disorders were pervasive, though regular physical activity appeared to reduce these risks to levels comparable with those of non-smokers.

Current American guidelines recommend adults engage in about 300 minutes of moderate physical activity or 150 minutes of vigorous activity each week, or an equivalent combination. The study, published in Health Education & Behavior, suggested that adhering to these guidelines can make a measurable difference for smokers in mid and later life, protecting against the adverse effects of both depression and poor sleep.

Lead author Taehyun Roh, an assistant professor in the Department of Epidemiology and Biostatistics, explained the interplay between these conditions: “Each of these has interconnected physiological and psychological pathways that potentially could affect the others. The neurochemical changes triggered by smoking can make depressive symptoms worse, which in turn can harm sleep quality, while physical activity can improve both conditions.”

The analysis drew on data from 3,008 adults in the United States, taken from the 2017–2020 National Health and Nutrition Examination Survey (NHANES), a nationwide study conducted annually by the Centres for Disease Control and Prevention. While the benefits of exercise were evident for older smokers, the results were more complex among younger adults. Smokers aged 20 to 39 who exercised regularly continued to report higher rates of sleep disorders compared with non-smokers, a finding the researchers believe may be linked to the severity of smoking habits or the timing and type of exercise.

Smoking remains the leading preventable cause of death worldwide, strongly associated with diseases such as lung cancer and chronic obstructive pulmonary disease. In the United States, nearly one in five adults smokes, while one in three experiences sleep disorders and one in twelve reports depressive symptoms. The findings of this study underline the importance of both regular physical activity and smoking cessation, highlighting that while exercise can mitigate some of the health risks faced by smokers, quitting remains the most effective step towards long-term well-being.

More information: Jeong-Hui Park et al, Impact of Physical Activity on Smoking, Sleep Disorders, and Depression Among U.S. Adults, Health Education & Behavior. DOI: 10.1177/10901981251362818

Journal information: Health Education & Behavior Provided by Texas A&M University

Parkinson’s disease in older adults is linked to increased brain amyloid without dementia

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A research article published on 6 August 2025 in Aging-US (Volume 17, Issue 8) is entitled “Age-related trends in amyloid positivity in Parkinson’s disease without dementia.” The study, led by first author Keiko Hatano and corresponding author Masashi Kameyama of the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan, examined how age influences the prevalence of amyloid accumulation in individuals with Parkinson’s disease (PD) who do not present with dementia.

The researchers reported that patients diagnosed with PD in their eighties exhibited a markedly higher rate of amyloid positivity—an indicator commonly associated with Alzheimer’s disease—compared with those diagnosed at a younger age. Crucially, none of the participants had developed dementia at the time of assessment. This finding suggests that older individuals with PD may be at increased risk of subsequent cognitive decline and may benefit from early screening for Alzheimer ‘s-related pathological changes.

Amyloid-beta is widely recognised as a key biomarker of cognitive impairment. Although its role in the development of PD with dementia is well established, its contribution in patients who remain cognitively intact has been less clear. The aim of this investigation was therefore to clarify the impact of age on amyloid accumulation in PD patients without dementia.

The study included 89 participants diagnosed with PD but free of dementia, who were stratified into two age groups: those diagnosed before the age of 73 (LOW group) and those diagnosed at 73 years or older (HIGH group). Cerebrospinal fluid samples were analysed to measure amyloid-beta concentrations, a standard approach for detecting early Alzheimer ‘s-related changes. Results showed that 30.6% of the older cohort tested positive for amyloid, in contrast to only 10.0% of the younger group. As the authors summarised: “[…] we elucidated the prevalence of amyloid positivity in patients with PD without dementia, whose mean age at diagnosis was 80.2 years, using CSF Aβ42 levels.”

One unexpected observation was that amyloid positivity was less frequent among PD patients of both age groups compared with cognitively normal older adults in the general population. This counterintuitive result suggests that Parkinson’s disease may alter the trajectory of amyloid accumulation, potentially shortening the preclinical phase during which amyloid silently builds up in the brain before symptoms emerge. The authors propose that this dynamic may hasten the progression from preserved cognition to dementia in PD. The study further identified age-related associations with other Alzheimer ’s-related biomarkers, including elevated tau protein levels.

Against the backdrop of global population ageing and the increasing prevalence of PD among older adults, these findings carry important implications. They highlight the value of biomarker screening to identify individuals at risk of accelerated cognitive decline and emphasise the need for therapeutic strategies aimed at delaying or preventing the onset of dementia in Parkinson’s disease.

More information: Keiko Hatano et al, Age-related trends in amyloid positivity in Parkinson’s disease without dementia, Aging-US. DOI: 10.18632/aging.206297

Journal information: Aging-US Provided by Impact Journals LLC

Cooling forearms in water may safeguard older adults during dangerous heatwaves

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When air conditioning is unavailable during extreme heat, millions of older adults and other vulnerable groups face a significantly heightened risk of cardiac complications and heat-related illnesses. Researchers from the Department of Kinesiology at Penn State have explored a straightforward and low-cost intervention to address this challenge. Their new study, published in Experimental Physiology, shows that immersing the hands and forearms in room-temperature tap water, at around 68 degrees Fahrenheit, can effectively cool older adults and ease strain on the heart during dangerously hot conditions.

Older adults are especially susceptible to the health consequences of heat because the body’s natural cooling mechanisms decline with age. Rachel Cottle, lead author of the study and now a postdoctoral fellow at the University of Texas Southwestern Medical Center, explained that older individuals sweat less efficiently and circulate blood to their skin less effectively compared to younger people. This makes them more vulnerable to overheating, which in turn contributes to the strikingly high mortality rates observed among older populations during heat waves. Even modest reductions in body temperature, she stressed, can be critical in protecting against heat-related harm.

To test their hypothesis, the researchers recruited twelve healthy participants over the age of sixty-five. Each volunteer was exposed to two hours in a hot and humid chamber set at 93 degrees Fahrenheit with 77% humidity—conditions designed to mimic the environmental stress of a severe heat wave. In some trials, participants submerged their hands and forearms up to the elbow in tap water for ten minutes, and then repeated the process once more after twenty minutes. In other trials, they sat in the chamber with no cooling intervention. Every participant completed the protocol four times, twice with water immersion and twice without. This design mirrored a realistic scenario in which an individual might fill a sink with water and reuse it during a power outage.

The results were telling. Water immersion reduced participants’ core body temperature by roughly half a degree Fahrenheit and, importantly, lowered heart rate. While the numerical drop in temperature may appear modest, it represented a meaningful reduction in thermal strain. More significant still was the decline in heart rate, which directly reduces cardiovascular stress. Because most heat-related deaths in older adults are tied to cardiac events, easing the workload on the heart through such a simple measure could make a tangible difference in survival outcomes during heat emergencies.

Despite the promise of this method, the researchers cautioned against seeing hand and forearm immersion as a first-line strategy. Larry Kenney, senior author of the study and professor of physiology and kinesiology at Penn State, emphasised that the priority during heat waves should always be to reduce overall heat exposure. Moving to an air-conditioned environment—whether a friend’s house, a shopping centre, a library, or a designated cooling centre—remains the most effective approach. Staying hydrated is essential, and while fans can provide relief in certain conditions, they are useless during power outages and can worsen thermal stress when outdoor temperatures are extremely high.

The study highlights the increasing urgency of preparing for heatwaves, which are becoming more frequent and severe due to climate change. Power outages, driven by high demand for air conditioning, exacerbate the problem by removing the most reliable cooling tool. In such scenarios, simple strategies such as hand and forearm immersion could buy valuable time and reduce health risks. As Cottle noted, “If everyone takes precautions and looks out for older friends, family members, and neighbours, we can protect many of the most vulnerable people among us.”

More information: Rachel Cottle et al, Intermittent hand and forearm immersion in 20°C water attenuates thermal, cardiovascular, and perceptual strain in older adults during heat stress, Experimental Physiology. DOI: 10.1113/EP092789

Journal information: Experimental Physiology Provided by Penn State

Adaptive immunity in Alzheimer’s disease spotlighted by Chinese Medical Journal Review

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Alzheimer’s disease (AD) remains one of the most pressing health challenges of our time, affecting more than 55 million people worldwide and accounting for the vast majority of dementia cases. As populations age, the impact of AD grows steadily, placing enormous strain not only on individuals and their families but also on health systems and societies at large. Despite decades of intensive research, there is still no cure, and the treatments currently available provide only modest relief. Unravelling the root causes of the disease is therefore one of the great frontiers in modern medicine, and recent work has begun to cast new light on the role of the immune system in its development.

Traditionally, AD has been understood as a disorder driven by the accumulation of two key proteins in the brain: amyloid and tau. Amyloid forms sticky plaques that build up between nerve cells, while tau becomes twisted into tangles inside them. Together, these pathological changes disrupt communication between neurons and progressively erode memory and cognition. In addition, researchers have increasingly recognised that chronic brain inflammation contributes significantly to the disease process. This inflammation was long believed to arise primarily from the brain’s innate immune defences. Still, new findings suggest that the adaptive immune system—the body’s more specialised and long-term defence mechanism—also plays a critical part. This perspective broadens our understanding of AD and opens up new directions for treatment.

To advance this understanding, a team from the Department of Neurology at Fujian Medical University Union Hospital and the Fujian Key Laboratory of Molecular Neurology in China reviewed decades of scientific work examining the involvement of adaptive immunity in AD. Led by Dr Xiaochun Chen, their findings were published in the Chinese Medical Journal on 5 August 2025. Dr Chen emphasised that while the focus of AD research has historically been on amyloid, tau, and innate immunity, their review demonstrates that T cells and B cells—key players in adaptive immunity—are also deeply implicated. This recognition has profound implications, suggesting that Alzheimer’s should be understood as not only a disease of protein misfolding but also one of immune imbalance.

The adaptive immune system is designed to provide targeted, long-lasting defence, mainly through the activity of T and B cells. In AD, evidence suggests that these cells may cross into the brain through a weakened blood–brain barrier, and once inside, they engage in a range of interactions with neural tissue. Specific T cells release inflammatory signals that appear to accelerate damage, while others may counteract harm and offer protection. Similarly, B cells have a dual role: in some instances, they fuel harmful immune responses, but they can also aid in clearing toxic proteins. Dr Chen described this as a “double-edged sword,” where immune cells may simultaneously exacerbate degeneration and provide opportunities for resilience. Understanding how to shift this balance in favour of protective effects is a key challenge for future research.

This shift in perspective has significant therapeutic implications. Recent years have seen considerable debate surrounding immunotherapies targeting amyloid, such as aducanumab and lecanemab, which have yielded mixed outcomes and sparked controversy over their safety and efficacy. The review suggests that broadening the focus to include adaptive immunity could lead to more effective interventions. Potential strategies involve rebalancing the activity of T and B cells, designing vaccines, or tailoring immune-based treatments to individuals with specific genetic risk factors. Such approaches move the field closer to precision medicine, offering the hope of more durable and personalised benefits for patients.

Despite these promising insights, many questions remain. Researchers are still working to clarify how immune cells breach the brain’s protective barriers, why their behaviour varies so markedly among patients, and how age-related changes in the immune system intersect with the biology of AD. These unanswered questions underscore the complexity of the disease but also point to new opportunities for innovation. As Dr Chen observed, adaptive immunity has moved from the margins of Alzheimer’s research to the centre stage. By embracing this broader understanding, scientists may one day harness the immune system not only to slow but perhaps even to prevent AD, providing much-needed hope to patients, families, and the healthcare systems struggling with its growing burden.

More information: Xiaochun Chen et al, Adaptive immunity in the neuroinflammation of Alzheimer’s disease, Chinese Medical Journal. DOI: 10.1097/cm9.0000000000003695

Journal information: Chinese Medical Journal Provided by Chinese Medical Journals Publishing House Co., Ltd.

Exploring the Role of Physical Frailty in Dementia Onset

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A major new study has provided fresh insight into the connection between physical frailty and dementia, suggesting that frailty may not only be associated with, but could also contribute directly to, the development of the disease. The findings were published on September 17, 2025, in Neurology®, the medical journal of the American Academy of Neurology. This large-scale investigation strengthens the case for understanding frailty as more than a sign of general health decline and positions it as a possible risk factor for dementia itself.

Frailty, in medical terms, was defined in the study as the presence of at least three out of five key symptoms: persistent tiredness, low physical activity, slower walking speed, reduced grip strength, and unintended weight loss. These indicators have long been recognised as markers of physical decline, but the research team sought to explore whether they might also be linked to long-term cognitive changes. “We have known that frailty is tied to a higher risk of dementia,” explained lead author Yacong Bo, PhD, of Zhengzhou University in China. “Our study provides evidence that frailty may actually be a cause, though it is still possible that frailty represents early changes in the disease process.”

The research drew on health data from an impressive cohort of 489,573 participants, with an average age of 57, who were followed for approximately 14 years. Among these individuals, 4.6% were classified as frail, 43.9% fell into the “pre-frailty” category with one or two symptoms, and just over half—51.5%—showed no symptoms and were deemed not frail. Over the course of the study, 8,900 people went on to develop dementia. The rates varied noticeably by frailty status: 4.6% among the frail group, 2.2% among the pre-frail, and 1.3% among those with no frailty symptoms.

When the researchers accounted for other factors that influence dementia risk, such as age, education level, and physical activity, they found striking differences. Those classified as frail were nearly three times more likely to develop dementia than those without any symptoms. Pre-frailty also carried a significant risk, with affected individuals showing a 50% higher likelihood of developing dementia compared to their non-frail peers. Genetic factors added further weight: people who were frail and also carried dementia-related genes faced nearly four times the risk of dementia compared with those who had neither frailty nor genetic predisposition.

Notably, the data suggested that frailty may play a causal role rather than being a by-product of dementia. The researchers examined brain imaging and biological markers, discovering that frail participants were more likely to show structural brain changes linked to dementia. “These biomarkers may be the mechanism that connects frailty to dementia,” noted Bo. At the same time, the reverse relationship appeared weak, with evidence showing dementia did not significantly increase the likelihood of becoming frail.

The study highlights the importance of recognising and addressing frailty as a potential avenue for dementia prevention. Early identification of frailty, along with interventions that promote physical activity, adequate nutrition, and muscle strength, serves a dual purpose: protecting physical function and safeguarding brain health. The authors acknowledge some limitations, particularly that four of the five frailty symptoms were self-reported and could be subject to inaccuracies. Nevertheless, the findings lend significant weight to the growing body of evidence that maintaining physical resilience is essential for cognitive well-being in later life.

More information: Yacong Bo et al, Association of Frailty With Dementia and the Mediating Role of Brain Structure and Immunometabolic Signatures, Neurology. DOI: 10.1212/WNL.0000000000214199

Journal information: Neurology Provided by American Academy of Neurology

Loneliness remains disproportionately high for working-age adults with disabilities, new study finds

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Working-age adults with disabilities experience far greater levels of loneliness than their peers without disabilities, according to a new study from researchers at Brown University’s School of Public Health and the Warren Alpert Medical School. The findings reveal that nearly one in three adults with disabilities between the ages of 18 and 64 reported persistent feelings of loneliness in a national survey, where participants were asked how often they felt a lack of companionship, left out, or isolated. Alarmingly, around two-thirds of respondents indicated that they frequently experienced severe loneliness, a burden that cut across all types of disability.

The study highlights an often-overlooked public health challenge. While loneliness is widely recognised as a risk factor for illness and premature mortality, there has been limited research examining how it affects people with disabilities, particularly those under the age of 65. The authors suggest that structural and social barriers, which restrict disabled people’s full participation in employment, community life and daily activities, likely intensify their susceptibility to loneliness. These constraints, they argue, may create conditions where isolation becomes not just a personal struggle but a systemic issue with profound health implications.

“Loneliness is known to be a risk factor for morbidity and mortality, but there is sparse research about loneliness among people with disabilities, especially in the age group of adults younger than 65,” said Melissa A. Clark, professor of health services, policy and practice, and director of the Survey, Qualitative and Applied Data (SQuAD) Research Core. “Our study calls attention to the need for further research focused on working-age adults with disabilities, both to characterise the factors driving their exceptionally high loneliness burden and to mitigate downstream health consequences.”

The study, published in Annals of Internal Medicine, analysed survey data from more than 3,800 working-age adults with disabilities who took part in the National Survey on Health and Disability. In one survey wave conducted between October 2019 and January 2020, 65% of respondents reported severe loneliness; in a second wave between October 2023 and February 2024, that number rose to 68%. The specific measures also revealed stark patterns: in the first and second waves, respectively, 30% and 33% reported often lacking companionship, 29% and 37% frequently felt left out, and 34% and 40% felt isolated.

These rates are dramatically higher than those observed in the broader population. Data from a nationally representative survey of more than 20,000 U.S. adults without disabilities found that only 8% reported frequently feeling left out or isolated, and just 10% said they often felt alone. Maggie Salinger, co-author of the study and assistant professor of medicine, explained: “We think people with disabilities may be predisposed to loneliness, since disability is a byproduct of social and structural barriers that restrict people’s access to full societal participation. We are worried that a disproportionately high degree of loneliness could compound the array of health disparities already known to affect people with disabilities.”

The authors conclude that addressing loneliness must be a priority within wider efforts to improve health equity for people with disabilities. Their findings suggest that public health strategies to tackle loneliness need to be not only broad in scope but also carefully adapted to reflect the diverse needs of people with different disability types. As Clark noted, “The loneliness crisis is already on public health officials’ radars. This study shows them how important it is to design loneliness interventions that are both accessible and tailored to people with varied disability types.”

More information: Maggie Salinger et al, Disproportionate Loneliness Burden Demonstrated in Two National Samples of Working-Age Adults With Varied Disability Types, Annals of Internal Medicine. DOI: 10.7326/ANNALS-25-00928

Journal information: Annals of Internal Medicine Provided by Brown University

Study finds retirement’s mental health boost not equally experienced

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Retirement has long been imagined as a time of freedom and rest, but new research suggests the psychological benefits of leaving work are far from universal. A study led by the University of Edinburgh has found that the impact of retirement on mental wellbeing is shaped by factors such as income, job type, marital status, and the age at which people retire. While most individuals do experience a lift in mental health after stepping away from work, some groups face a far more uneven journey.

The analysis, which drew on surveys from 1,583 Dutch participants collected between 2007 and 2023, tracked people’s mental health across three phases: the years leading up to retirement, the transition itself, and the years afterwards. Using the Mental Health Inventory, which measures psychological wellbeing alongside symptoms of anxiety and depression, the researchers assessed changes across an average retirement age of 66 to 67. The findings reveal that not only does retirement affect individuals differently, but its benefits may also fade with time.

Low-income retirees reported the poorest outcomes overall. Although their mental health improved when they first left work, these gains were short-lived, with many experiencing a decline around two and a half years into retirement. People on average incomes saw more substantial improvements in wellbeing before retirement and modest gains afterwards, though those in physically demanding jobs consistently fared worse than their peers. High-income earners showed little change in their mental health before leaving work but experienced a sharp boost once they retired; however, those who prolonged their careers experienced slower improvements, suggesting that delayed retirement may blunt its mental health benefits.

Beyond income and occupation, social and demographic factors played a significant role. Women, unmarried individuals, and those on low incomes at the point of retirement all reported substantially lower mental health scores compared with other groups. These disparities highlight how retirement is intertwined with broader social inequalities, influencing the extent to which people can enjoy later life.

The study is among the first to evaluate retirement as a process rather than a single moment, offering insights into how wellbeing evolves. Following people across a span of more than a decade highlights the complex interplay between financial security, job conditions, personal circumstances, and the timing of retirement. Importantly, it shows that mental health trajectories can diverge sharply depending on the resources and resilience individuals bring with them into this new stage of life.

Researchers argue that these findings carry important implications for policymakers. Targeted interventions help address the risks faced by vulnerable groups, particularly those with low incomes or high job demands, who are less likely to experience lasting benefits from retirement. As populations continue to age and debates over raising retirement ages intensify, understanding these differences will be crucial in ensuring that the rewards of retirement are more evenly shared.

More information: Xuefei Li et al, Mental health trajectories surrounding retirement: A longitudinal perspective, SSM – Mental Health. DOI: 10.1016/j.ssmmh.2025.100470

Journal information: SSM – Mental Health Provided by University of Edinburgh

FAU study finds lifestyle changes can slow cognitive decline

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An estimated 7.2 million Americans over the age of 65 are currently living with Alzheimer’s disease (AD). By 2060, that figure is projected to rise to nearly 13.8 million. These stark numbers reflect more than just demographic ageing; they signal a public health emergency that calls for urgent, proactive responses. While advancing age is the strongest predictor of cognitive decline, research has shown that losing cognitive function is not an unavoidable part of the ageing process.

As the prevalence of Alzheimer’s and related dementias grows at an alarming pace, researchers from Florida Atlantic University’s Charles E. Schmidt College of Medicine argue that prevention strategies must move beyond reliance on pharmacological treatments. In a recent commentary published in The American Journal of Medicine, authors call on clinicians, policymakers, and public health leaders to embrace lifestyle-based interventions as an underutilised yet powerful means of reducing the burden of cognitive decline, both in the United States and globally.

Charles H. Hennekens, M.D., co-author of the commentary and the First Sir Richard Doll Professor of Medicine and Preventive Medicine, highlighted the urgency of this approach: “While deaths from cardiovascular disease have declined since 2000, deaths from Alzheimer’s disease have surged by more than 140%. At the same time, it is estimated that as much as 45% of dementia risk may be linked to modifiable lifestyle and environmental factors.” His point underscores how small but widespread behavioural changes could have profound effects on population health.

The commentary stresses that lifestyle factors—such as physical inactivity, poor diet, obesity, alcohol use, hypertension, diabetes, depression, and social or intellectual isolation—play a pivotal role in determining dementia risk. The authors note that the very same therapeutic lifestyle changes already proven to reduce cardiovascular disease, cancer and other chronic illnesses may also improve brain health, and that when multiple risks are targeted simultaneously, their combined impact can be substantial.

Robust scientific evidence supports this view. The researchers highlight the POINTER trial, the first large-scale U.S.-based randomised study to evaluate lifestyle changes in older adults at elevated risk of cognitive decline. Participants who engaged in a structured programme—incorporating regular exercise, a hybrid Mediterranean–DASH diet, cognitive training, and social engagement—showed clinically meaningful improvements in global cognition over two years. Gains were particularly evident in executive functions, including memory, attention, and decision-making.

These findings closely align with the results from the Finnish FINGER trial, which also demonstrated that multidomain lifestyle interventions can improve cognitive outcomes in at-risk populations. Together, the two studies provide compelling evidence that the same strategies known to protect the heart and reduce cancer risk may also preserve brain function. According to Hennekens, these results suggest that lifestyle changes can be a “transformative” tool for brain health.

The biological mechanisms underpinning these benefits are increasingly well understood. Exercise stimulates the release of brain-derived neurotrophic factor, which promotes hippocampal growth, while also enhancing blood flow and reducing inflammation. Healthy dietary patterns lower oxidative stress and improve insulin sensitivity, while quitting smoking helps preserve the structural integrity of the brain. Regular social interaction and cognitive activity enhance neuroplasticity, thereby building resilience against cognitive decline. These mechanisms provide a clear scientific rationale for why lifestyle interventions can be so effective.

Finally, the implications for policy, health systems and society are profound. Pharmacological treatments for dementia are costly, often offer modest benefits, and may cause side effects ranging from headaches to serious complications. In contrast, lifestyle interventions are low-risk, cost-effective and broadly beneficial. Modelling studies suggest that reducing key risk factors by even 10% to 20% each decade could cut the burden of cognitive decline by up to 15%. With the societal cost of dementia care already exceeding $400 billion annually in the United States alone, the researchers argue that investing in preventive, lifestyle-focused strategies represents one of the most powerful tools available to mitigate the personal and economic toll of cognitive decline.

More information: John Dunn et al, Prospects for Clinicians to Reduce Cognitive Decline in Elderly Patients, The American Journal of Medicine. DOI: 10.1016/j.amjmed.2025.08.042

Journal information: The American Journal of Medicine Provided by Florida Atlantic University