Category: Ageing

Number of Steps Matters More for Older Women’s Health than the Frequency

4000 steps once/twice weekly is associated with 26% lower risk of death rising to 40% if done on 3 days of the week – but it’s daily step count rather than number of days that matters, findings suggest 

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Clocking up at least 4000 daily steps on just 1 or 2 days per week is linked to a lower risk of death and cardiovascular disease among older women, according to research published online in the British Journal of Sports Medicine.

This large prospective study examined not only how many steps older women take but how often they reach their step targets across the week, addressing a key gap in current physical activity guidelines.

Researchers found that achieving at least 4000 steps per day on 1-2 days per week was associated with a significantly lower risk of death and lower risk of cardiovascular disease (CVD), compared with not reaching this level on any day.

A large body of evidence shows that lifelong physical activity is important for improving the healthspan, say the researchers. But it’s not entirely clear how much physical activity people should do as they age to reap appreciable health benefits, particularly in respect of step counts which are yet to make it into physical activity guideline recommendations, they add.

To explore this further, they set out to look at the associations between daily step counts of between 4000 and 7000 and death from all causes and from cardiovascular disease in older women.

They also wanted to find out if the total number of daily steps might drive any observed associations, rather than the frequency of achieving step count thresholds, with a view to informing future guidelines–in particular the US Physical Activity Guidelines, the next edition of which is planned for 2028.

The study followed 13547 women (average age 71) from the US Women’s Health Study who wore accelerometers (activity trackers) for seven consecutive days between 2011–2015 and were tracked for nearly 11 years. The women were free of cardiovascular disease or cancer at the start of the study.

During the monitoring period of nearly 11 years up to the end of 2024, 1765 women (13%) died and 781 (5%) developed cardiovascular disease.

Clocking up at least 4000 steps/day on 1–2 days of the week was associated with a 26% lower risk of death from all causes and a 27% lower risk of a cardiovascular disease death compared with not reaching this threshold on any day of the week.

For those achieving this step count on at least 3 days of the week, the lower risk of death from any cause increased to 40%, but remained at 27% for the risk of cardiovascular death.

But while higher daily step counts of 5000 to 7000 on 3 or more days of the week were associated with a further fall in all-cause mortality risk (32%) they were associated with a levelling out in cardiovascular disease mortality risk (16%).

When the findings were adjusted to take account of average daily steps, previously observed associations weakened, suggesting that [average] steps is the key driver of the protective effect, suggest the researchers.

This is an observational study, and as such, no firm conclusions can be drawn about cause and effect. The researchers also acknowledge that physical activity was assessed only for 1 week, and therefore couldn’t account for variations in behaviour over longer periods, nor did they have information on dietary patterns.

Nevertheless, they suggest: “The present study….suggests that frequency of meeting daily step thresholds is not critical (even 1–2 days/week of ≥4000 steps/day was related to lower mortality and CVD), and that step volume is more important than the frequency of meeting daily step thresholds in the older population.”

And they go on to explain: “An important translational implication of these findings is that since step volume is the important driver of the inverse associations, there is no ‘better’ or ‘best’ pattern to take steps; individuals can undertake [physical activity] in any preferred pattern (eg, ‘slow and steady’ vs ‘bunched patterns’) for lower mortality and CVD risk, at least among older women.”

They conclude: “These findings provide additional evidence for considering including step metrics in the next [physical activity] guidelines, and that ‘bunching’ steps is a viable option for health.”

Source: BMJ Group

New Evidence that Stress Alters Metabolic Hormone with Health Consequences

A new biomarker for mental health called FGF21 offers a window into aging and disease risk

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A long-studied metabolic hormone, FGF21, also acts as a stress hormone – a discovery that helps explain how psychological stress causes metabolic dysregulation and drive physical disease, according to a new study published in Nature Metabolism.

FGF21 (fibroblast growth factor 21) has been researched for over two decades for its role in metabolism, glucose regulation, and diabetes. 

The new findings, from researchers at Columbia University Mailman School of Public HealthVagelos College of Physicians and Surgeons, and the Butler Columbia Aging Center, show for the first time that psychological stress acutely alters FGF21 levels in the bloodstream, highlighting the hormone’s potential to link mental states to metabolic responses and ultimately affect overall health and biological aging.

“This is the first human evidence that FGF21 responds to mental stress, acting as a hormonal bridge between body and mind,” said senior author Martin Picard, PhD, associate professor of behavioural medicine at Columbia and co-director of the Columbia Science of Health programme. “It integrates psychosocial experiences with systemic metabolic signalling – expanding the neuroendocrine framework beyond traditional stress hormones.”

The study tracked hormonal changes following acute psychological stress in both healthy individuals and patients with mitochondrial disease, a group of genetic disorders that impair cellular energy transformation. In healthy participants, FGF21 levels on average dropped immediately after exposure to a standardised stressor, returning to baseline within 90 minutes – demonstrating a tightly regulated, dynamic hormonal pattern.

In contrast, participants with mitochondria that cannot transform energy normally showed a different pattern: FGF21 levels rose following stress and peaked at 90 minutes, indicating a fundamentally different stress response, likely regulated by mitochondrial biology.

“These results reveal a new axis of vulnerability,” said Mangesh Kurade, lead author on the study at Columbia. “The way our social environment and psychological experiences interact with mitochondrial health may directly shape metabolic outcomes and long-term disease risk.”

To validate their findings, the team analysed data from more than 20 000 participants in the UK Biobank and also drew on data from their ongoing MiSBIE study (Mitochondrial Stress and Biomarkers in Emotion), which investigates how psychosocial variables map onto biological processes.

The results showed that loneliness, childhood neglect, or recent relationship breakdowns including marital separation was linked to higher FGF21, while individuals with stronger social ties and emotional well-being – including frequent social interactions and high couple satisfaction and social support, were associated with lower levels – providing population-level evidence that FGF21 tracks with psychosocial conditions.

“Our findings suggest that the stress hormone and mitochondrial disease biomarker FGF21 signals not just acute stress, but also reflects a person’s social and emotional life over time,” said co-author Michio Hirano, MD, professor of Neurology at Columbia University Irving Medical Center who led the clinical portion of the study.

This cross-validation strengthens the case for FGF21 as a reliable biomarker of how psychological and social environments shape metabolic biology and perhaps also the clinical trajectory of mitochondrial diseases. By identifying FGF21 as both a biological mediator and potential biomarker of psychological stress, the study opens new avenues for research and clinical monitoring.

“This study bridges traditionally separate fields – metabolism and stress biology – suggesting that future precision mental health strategies may benefit from incorporating FGF21 and other biomarkers to monitor metabolic stress vulnerability and therapeutic responses,” said Kurade.

As a hormone once studied strictly within metabolic disease contexts, FGF21 now appears to straddle the boundary between mind and body, offering biological insight into how we age, adapt, and break down under pressure.

“This is about more than a single hormone,” said Picard, who is also associate professor at the Columbia Butler Aging Center. “It’s about understanding how our lived experience – our relationships, our stress, our resilience – gets translated into biology. A more accurate, holistic picture of human health is emerging. It’s an exciting time for science and medicine.”

Source: Columbia Mailman School of Public Health

Quitting Smoking Late in Life May Still Slow Cognitive Decline

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Quitting smoking in middle age or later is linked to slower age-related cognitive decline over the long term, according to a new study by UCL researchers.

The study, published in The Lancet Healthy Longevity, looked at data from 9436 people aged 40 or over (average age: 58) in 12 countries, comparing cognitive test results among people who quit smoking with those of a matched control group who kept smoking.

The research team found that the cognitive scores of those who had quit smoking declined significantly less than their smoking counterparts in the six years after they quit. For verbal fluency, the rate of decline roughly halved, while for memory it slowed by 20%.

Since slower cognitive decline is related to reduced dementia risk, their findings add to a growing body of evidence suggesting quitting smoking might be a preventative strategy for the disease. Still, more research is needed to confirm this.

Lead author Dr Mikaela Bloomberg (UCL Institute of Epidemiology & Health Care) said: “Our study suggests that quitting smoking may help people to maintain better cognitive health over the long term even when we are in our 50s or older when we quit.

“We already know that quitting smoking, even later in life, is often followed by improvements in physical health and well-being. It seems that, for our cognitive health too, it is never too late to quit.

“This finding is especially important because middle-aged and older smokers are less likely to try to quit than younger groups, yet they disproportionately experience the harms of smoking. Evidence that quitting may support cognitive health could offer new compelling motivation for this group to try and quit smoking.

“Also, as policymakers wrestle with the challenges of an ageing population, these findings provide another reason to invest in tobacco control.”

Smoking is thought to harm brain health in part because it affects cardiovascular health – smoking causes damage to blood vessels that supply oxygen to the brain. Smoking is also thought to affect cognitive health by causing chronic inflammation and directly damaging brain cells through oxidative stress (due to the creation of unstable molecules called free radicals).

Co-author Professor Andrew Steptoe (UCL Institute of Epidemiology & Health Care) said: “Slower cognitive decline is linked to lower dementia risk. These findings add to evidence suggesting that quitting smoking might be a preventative strategy for the disease. However, further research will be needed that specifically examines dementia to confirm this.”

Previous studies, the researchers noted, had found a short-term improvement in cognitive function after people stopped smoking. But whether this improvement was sustained over the longer term – particularly when people quit smoking later in life – was not known.

To answer this question the research team looked at data from three ongoing studies* where a nationally representative group of participants answered survey questions every two years. The studies covered England, the US, and 10 other European countries.

More than 4,700 participants who quit smoking were compared with an equal number of people who carried on smoking. The two groups were matched in terms of their initial cognitive scores and other factors such as age, sex, education level, and country of birth.

The research team found that the two groups’ scores in memory and verbal fluency tests declined at a similar rate in the six years prior to participants of one group quitting smoking. These trajectories then diverged in the six years following smoking cessation.

For the smokers who quit, the rate of decline was about 20% slower for memory and 50% slower for verbal fluency. In practical terms, this meant that with each year of ageing, people who quit experienced three to four months less memory decline and six months less fluency decline than those who continued smoking.

This was an observational analysis, so unmeasured differences between smokers who quit and continuing smokers could remain; while the trends before quitting were similar, the study cannot prove cause and effect.

However, the research team noted their findings were consistent with earlier studies showing that adults aged over 65 who quit smoking during early- or mid-life have comparable cognitive scores to never smokers, and that former and never smokers have a similar risk of dementia a decade or longer after quitting.

*The longitudinal studies were the English Longitudinal Study of Ageing (ELSA), the Survey of Health, Ageing and Retirement in Europe (SHARE), and the Health and Retirement Study (HRS).

Source: University College London

Link Between Calcium Supplements and Dementia Debunked by New Research

New research has found no evidence that calcium monotherapy increases the long-term risk for dementia.

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New research from Edith Cowan University (ECU), Curtin University and the University of Western Australia has found no evidence that calcium monotherapy increases the long-term risk for dementia, helping to dispel previous concerns about its potential negative effects on brain health in older women.

This study, which leveraged outcomes from prior research that provided calcium supplements or a placebo to 1460 older women over a five-year period, found that the supplement did not increase the long-term risk of dementia.

“Calcium supplements are often recommended to prevent or manage osteoporosis,” said ECU PhD student Ms Negar Ghasemifard.

Around 20 per cent of women over the age of 70 are affected by osteoporosis and calcium supplementation is widely recommended as a preventative measure against fracture.

“Previous research has raised concerns around the impacts that calcium supplements could have on cognitive health, particularly dementia. Results from our study provides reassurance to patients and clinicians regarding the safety of calcium supplements in the context of dementia risk for older women,” Ms Ghasemifard said.

ECU Senior Research Fellow Dr Marc Sim noted that when the analysis was adjusted for supplement compliance, a range of lifestyle factors, including dietary calcium intake and genetic risk, the results remained unchanged.

“Previous research suggesting potential links between calcium supplement use and the risk for dementia was purely observational in nature. Our research, in comparison, consisted of a post-hoc analysis from a 5-year double-blind, placebo controlled randomised clinical trial on calcium supplements to prevent fracture. Whilst our study is still epidemiology, its design does reduce the likelihood of unmeasured confounding”

“Some 730 older women were given calcium supplements over five years, and a further 730 were given placebo. This study design offers more accurate data on dosage and duration, and we had a long follow-up period of 14.5 years, which strengthens our results,” Dr Sim said.

While these findings may alleviate concerns regarding calcium supplementation and all-cause dementia risk in older women, particularly after the age of 80 years, Professor Simon Laws, Director of ECU’s Centre for Precision Health, said further research was required.

“Whether this extrapolates to other demographics, such as men or even women commencing supplementation earlier in life, remains unknown. To confirm the current findings, particularly regarding brain health, and to address these population gaps, future clinical trials of calcium supplements, with or without vitamin D, would need to be undertaken. These should include specific and robust assessments of brain health as the primary outcome measures.”

Curtin University’s Professor Blossom Stephan, Director of the Dementia Centre of Excellence and a Dementia Australia Honorary Medical Advisor said the research highlighted a very important finding that provides reassurance to clinicians and patients about the long-term safety of calcium supplementation.

“Given calcium’s critical role in multiple physiological functions, including bone health, these results provide reassurance that long-term calcium supplementation did not increase dementia risk in older women,” she said.

Source: Edith Cowan University

Global Study Challenges Age-Based Treatment Decisions in Leukaemia

Study of 2,800 patients suggests moving beyond chronological cut-offs in cancer care

SAG Leukaemia. Credit: Scientific Animations CC0

An international study conducted by the Alliance for Clinical Trials in Oncology and the Acute Myeloid Leukemia Cooperative Group reveals that age-based classifications in the treatment of acute myeloid leukaemia (AML) may be outdated and overly simplistic.

AML is a fast-growing cancer of the blood and bone marrow that disproportionately affects older adults. Historically, age has been a key factor in determining treatment intensity, eligibility for clinical trials, and access to targeted therapies. However, this new research suggests that age alone is not a reliable indicator of disease biology or prognosis.

“Our findings support a more flexible, biology-driven approach to AML treatment and trial design. Age alone should not be a gatekeeper to potentially life-saving therapies,” said Alliance researcher and lead author Ann-Kathrin Eisfeld, MD, associate professor of Internal Medicine and director of the Clara D. Bloomfield Center for Leukemia Outcomes Research at The Ohio State University. “Our results suggest reconsidering age-based eligibility criteria for treatments. By focusing on molecular and genetic profiles rather than chronological age, clinicians may better tailor treatments to individual patients, improving outcomes and expanding access to novel therapies.”

Published in Leukemiathe study analysed data from 2823 adult AML patients treated in the setting of large cooperative group frontline trials across the United States (CALGB/Alliance) and Germany (AMLCG), uncovering nuanced age-related trends in genetic mutations and survival outcomes that challenge current clinical practices. This research is the first large-scale, cross continental study to analyse the mutational patterns and outcomes among patients of all age groups with AML.

The analysis included patients treated with frontline cytarabine-based chemotherapy between 1986 and 2017. Molecular profiling was conducted using targeted sequencing platforms, and survival outcomes were assessed using the 2022 European LeukemiaNet (ELN) genetic-risk classification.

The study found no clear age threshold that could biologically or prognostically separate patients into distinct groups. Instead, genetic mutations and survival outcomes varied continuously across the age spectrum. This challenges the long-standing practice of using arbitrary age cut-offs, such as 60 or 65 years, to guide treatment decisions.

Survival outcomes also declined steadily with age, even among patients classified as having favourable genetic risk. For example, patients aged 18 to 24 with favourable-risk AML had a five-year overall survival rate of 73%, while those aged 75 and older had a survival rate of just 21%. This trend was consistent across all risk categories, indicating that age negatively impacts prognosis regardless of genetic classification.

“This research arrives at a critical moment in oncology, as precision medicine continues to transform cancer care,” added Dr Eisfeld. “Most targeted treatment options are still only available for patients above a certain age threshold that is dictated by corresponding inclusion criteria of pivotal clinical trials, even though patients outside of that age range might equally benefit from these often less toxic treatments.”

Source: Alliance for Clinical Trials in Oncology

Small Reductions in Cholesterol Could Slash Risk of Dementia for Those with Certain Genetics

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Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomisation – this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimising the influence of confounding factors like weight, diet, and other lifestyle habits.

By comparing these individuals to individuals without these genetic variants, the researchers were able to measure differences in the risk of dementia. They found reducing the amount of cholesterol in the blood by a small amount (one millimole per litre) to be associated with up to 80% reduction in risk of developing dementia for certain drug targets.

“What our study indicates is that if you have these variants that lower your cholesterol, it looks like you have a significantly lower risk of developing dementia,” said Dr Nordestgaard, who now works in the Department of Clinical Biochemistry at Copenhagen University Hospital – Bispebjerg and Frederiksberg hospital.

The results suggest that having low cholesterol, whether due to genes or medical treatment, can help reduce the risk of dementia. However, the study does not say anything definitive about the effect of the medicine itself.  

One of the challenges is that dementia typically does not appear until late in life, and therefore research in the area typically requires a very long period of follow-up. 

It is still not known exactly why high cholesterol can increase the risk of dementia, but one possible explanation proposed by Dr Nordestgaard is that high cholesterol can lead to atherosclerosis. 

“Atherosclerosis is a result of the accumulation of cholesterol in your blood vessels,” Dr Nordestgaard said.  “It can be in both the body and the brain and increases the risk of forming small blood clots – one of the causes of dementia. 

“It would be a really good next step to carry out randomised clinical trials over 10 or 30 years, for example, where you give the participants cholesterol-lowering medication and then look at the risk of developing dementia,” Dr Nordestgaard added. 

The study used data from the UK Biobank, the Copenhagen General Population Study, the Copenhagen City Heart Study, the FinnGen study, and the Global Lipids Genetics Consortium.

Source: University of Bristol

Age-related Macular Degeneration Reversed in Mice with Polyunsaturated Fatty Acid

Retina showing reticular pseudodrusen. Although they can infrequently appear in individuals with no other apparent pathology, their highest rates of occurrence are in association with age-related macular degeneration (AMD), for which they hold clinical significance by being highly correlated with end-stage disease sub-types, choroidal neovascularisation and geographic atrophy. Credit: National Eye Institute

In a new study, UC Irvine researchers explore a possible therapy for addressing “aging” in the eye and for preventing diseases such as age-related macular degeneration (AMD).

“We show the potential for reversing age-related vision loss,” says Dorota Skowronska-Krawczyk, PhD, an associate professor in the Department of Physiology and Biophysics and the Department of Ophthalmology and Visual Sciences. The study was a collaboration between researchers from UC Irvine, the Polish Academy of Sciences, and the Health and Medical University in Potsdam, Germany.

They outline their findings in a paper published in Science Translational Medicine.

Understanding the “Aging” Gene

The work is a follow-up to an earlier study on Elongation of Very Long Chain Fatty Acids Protein 2 (ELOVL2), an established biomarker of age. “We showed that we have lower vision when this ELOVL2 enzyme isn’t active,” says Skowronska-Krawczyk, also a faculty member in the Robert M. Brunson Center for Translational Vision Research at the UC Irvine School of Medicine. In that work, the researchers found that enhancing ELOVL2 gene expression in aging mice boosted levels of the omega−3 fatty acid docosahexaenoic acid (DHA) in the eye and improved vision.

The more recent study sought to identify a way to bypass the need for the ELOVL2 enzyme.

As we age, changes in lipid metabolism lead to a decline in very-long-chain polyunsaturated fatty acids (VLC-PUFAs) in the retina, which in turn affects our vision and can lead to AMD. The ELOVL2 gene is a key enzyme in the production of VLC-PUFAs as well as DHA.

Injecting aged mice with the polyunsaturated fatty acid improved visual function. “It’s a proof-of-concept for turning lipid injection into a possible therapy,” says Skowronska-Krawczyk. “What is important is that we didn’t see the same effect with DHA.” Others have also questioned the ability of DHA to slow AMD progression.

“Our work really confirms the fact that DHA alone cannot do the work, but we have this other fatty acid that is seemingly working and improving vision in aged animals,” says Skowronska-Krawczyk. “We have also shown on a molecular level that it actually reverses the aging features.”

Furthermore, the researchers found genetic variants in the ELOVL2 enzyme that correlate with faster progression of AMD. “Now we actually have a genetic connection to the disease and its aging aspect,” says Skowronska-Krawczyk, “so we could potentially identify people at higher risk for vision loss progression.” This could lead to not only therapeutic treatment options but also targeted interventions for prevention.

These findings have only further solidified Skowronska-Krawczyk’s view of the importance of the ELOVL2 enzyme. “I am pretty convinced it’s one of the top aging genes that we should look at when we think about anti-aging therapies.”

Looking Beyond the Retina

In a collaboration with researchers from UC San Diego, Skowronska-Krawczyk has also started to explore the role of lipid metabolism in immune system aging. That study found that the lack of ELOVL2 enzyme induces accelerated aging of immune cells, suggesting that systemic lipid supplementation could potentially counteract the effects of age on the immune system. It also suggested that lipid metabolism might play a role in blood cancers.

“Our first study explored a potential therapy to address vision loss,” says Skowronska-Krawczyk, “but with the information we’ve since learned about immune aging, we are hopeful the supplementation therapy will boost the immune system as well.”

Source: University of California – Irvine

Does Prior Incarceration Contribute to Poor Health Later in Life?

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A recent analysis reveals that older adults with prior incarceration report worse physical and mental health than their peers, even if they were incarcerated in the distant past. The findings are published in the Journal of the American Geriatrics Society.

Among the 1318 US adults aged 50 years and older who responded to the Family History of Incarceration Survey, 21% had been incarcerated. Formerly incarcerated older adults were more likely to be men, non-Hispanic Black or “other” race/ethnicity, meet criteria for disability, be unmarried, and have lower income and education compared with those never incarcerated.

After adjusting for potentially confounding factors like demographics and socioeconomics, prior incarceration was associated with an approximately 90% higher odds of reporting “fair” or “poor” physical health. Length of time since incarceration did not moderate the association, meaning that even those incarcerated more than 10 years ago had equally poor self-reported health. The association with mental health was explained in part by income and employment.

The findings suggest that clinicians could consider screening for incarceration history and connecting formerly incarcerated patients to services and organisations that serve this community.

“Mass incarceration began in 1973, so older adults have spent most of their adult lives in this era and millions have been incarcerated in the past. It is critical to understand how incarceration – even in the distant past – may affect the health of older adults and what we can do to improve their health,” said corresponding author Louisa W. Holaday, MD, MHS, of the Icahn School of Medicine at Mount Sinai.

Source: Wiley

Poor Sleep May Accelerate Brain Ageing

Poor sleep may accelerate brain ageing, a new study shows. Photo by Andrea Piacquadio

People who sleep poorly are more likely than others to have brains that appear older than they actually are. This is according to a comprehensive brain imaging study from Karolinska Institutet, published in the journal eBioMedicine. Increased inflammation in the body may partly explain the association.

Poor sleep has been linked to dementia, but it is unclear whether unhealthy sleep habits contribute to the development of dementia or whether they are rather early symptoms of the disease. In a new study, researchers at Karolinska Institutet have investigated the link between sleep characteristics and how old the brain appears in relation to its chronological age. 

The study includes 27 500 middle-aged and older people from the UK Biobank who underwent magnetic resonance imaging (MRI) of the brain. Using machine learning, the researchers estimated the biological age of the brain based on over a thousand brain MRI phenotypes. 

Low-grade inflammation 

The participants’ sleep quality was scored based on five self-reported factors: chronotype (being a morning/evening person), sleep duration, insomnia, snoring, and daytime sleepiness. They were then divided into three groups: healthy (≥ 4 points), intermediate (2-3 points), or poor (≤ 1 point) sleep. 

“The gap between brain age and chronological age widened by about six months for every 1-point decrease in healthy sleep score,” explains Abigail Dove, researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, who led the study. “People with poor sleep had brains that appeared on average one year older than their actual age.” 

To understand how poor sleep can affect the brain, the researchers also examined levels of low-grade inflammation in the body. They found that inflammation could explain just over ten per cent of the link between poor sleep and older brain age. 

“Our findings provide evidence that poor sleep may contribute to accelerated brain ageing and point to inflammation as one of the underlying mechanisms,” says Abigail Dove. “Since sleep is modifiable, it may be possible to prevent accelerated brain ageing and perhaps even cognitive decline through healthier sleep.” 

Several possible explanations 

Other possible mechanisms that could explain the association are negative effects on the brain’s waste clearance system, which is active mainly during sleep, or that poor sleep affects cardiovascular health, which in turn can have a negative impact on the brain. 

Participants in the UK Biobank are healthier than the general UK population, which could limit the generalisability of the findings. Another limitation of the study is that the results are based on self-reported sleep. 

The study was conducted in collaboration with researchers from the Swedish School of Sport and Health Sciences, and Tianjin Medical University and Sichuan University in China, among others. It was funded by the Alzheimer’s Foundation, the Dementia Foundation, the Swedish Research Council, the Loo and Hans Osterman Foundation for Medical Research, and the Knowledge Foundation. The researchers report no conflicts of interest. 

Source: Karolinska Institutet

Is Physical Frailty a Cause of Dementia?

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A new study suggests that physical frailty may contribute to the development of dementia. The study was published on September 17, 2025, in Neurology®, the medical journal of the American Academy of Neurology.

Physical frailty is defined as having three or more of these five symptoms: often feeling tired; little or no physical activity; slow walking speed; low grip strength; and unintentional weight loss.

“We’ve known that frailty is associated with a higher risk of dementia, but our study provides evidence that frailty may be an actual cause of dementia,” said study author Yacong Bo, PhD, of Zhengzhou University in China. “On the other hand, despite this new evidence, we can’t rule out the possibility that frailty is instead a marker of the early changes in the disease process.”

The study involved 489 573 people with an average age of 57 who were followed for an average of 14 years. A total of 4.6% of the participants met the definition for frailty, with three or more of the symptoms. Another 43.9% who had one or two symptoms were categorised as pre-frailty and 51.5% had no symptoms and were categorised as not frail.

During the study, 8900 people developed dementia. A total of 4.6% of those with frailty developed dementia, compared to 2.2% of those with pre-frailty and 1.3% of those without frailty. After researchers adjusted for other factors that could affect the risk of dementia, such as age, education level and physical activity, they found that the people who met the definition for frailty were nearly three times more likely to develop dementia than those who had no symptoms of frailty.

Those categorised as pre-frailty were 50% more likely to develop dementia. People with frailty who also had genes linked to dementia were nearly four times more likely to develop dementia than those without frailty or the genetic risk. The researchers also analysed the data and found evidence suggesting that frailty may potentially be a factor in causing dementia.

“These findings reinforce the importance of identifying and managing frailty as a strategy for preventing dementia,” Bo said.

Looking at the data from the other direction, the researchers found that dementia is unlikely to increase the risk of frailty. The researchers also looked at brain imaging and biological biomarkers and found that people with frailty were more likely to have changes in their brain structure related to dementia.

“These biomarkers may be a mechanism underlying the pathway from frailty to dementia,” said Bo. A limitation of the study was that four of the five symptoms of frailty were reported by the participants, so they may not have provided accurate information.

Source: American Academy of Neurology