Ageing
An active midlife halves women’s risk of premature death

Women who stay active through midlife have about half the risk of early death from any cause as women who remain inactive, a study suggests.
Physical activity is known to bring a range of health benefits and lower the risk of chronic disease and premature death.
But most earlier studies measured activity at only one point in time, which does not show how exercise habits change over the years.
Binh Nguyen of the University of Sydney said: “Staying active throughout midlife can make a real difference for women’s long-term health.
“Our study shows that maintaining recommended levels of physical activity over multiple years helps protect against early death.”
The research used data from 11,169 women born between 1946 and 1951 who took part in the Australian Longitudinal Study on Women’s Health.
They were surveyed nine times between 1996 and 2019, about every three years. Researchers looked at how often they met the World Health Organization recommendation of at least 150 minutes of moderate-to-vigorous physical activity a week.
The study found that consistently meeting those recommendations through midlife was linked to a relative risk of death from any cause that was half that of women who consistently did not meet them.
In absolute terms, the death rate was 5.3 per cent among women who consistently met the guidelines, compared with 10.4 per cent among those who consistently did not.
The effect appeared similar, or possibly stronger, for deaths linked to cardiovascular disease and cancer, although those findings were less certain, possibly because fewer deaths from those causes were recorded.
Cardiovascular disease refers to conditions affecting the heart or blood vessels.
The evidence for starting to meet the recommendations later in midlife, at age 55, 60 or 65 rather than across all of midlife, was also uncertain and inconclusive.
The study was limited by the fact that physical activity was self-reported and that the sample may not represent all mid-aged Australian women.
The authors wrote: “This study supports the growing evidence that maintaining an active lifestyle in midlife provides health benefits.
“Women should be encouraged to meet physical activity recommendations throughout mid-age to derive these benefits.”
Diagnosis
Women with osteoporosis face increased Alzheimer’s risk, study suggests

Women with osteoporosis may be more likely to carry a gene linked to Alzheimer’s, according to new research.
Scientists found that APOE4, the most common genetic risk factor for Alzheimer’s, can weaken bone quality in women, even when standard scans appear normal.
The study, carried out by researchers at the Buck Institute for Research on Ageing in California, US, and UC San Francisco, suggests the gene may damage bone at a microscopic level long before any visible signs.
These changes can emerge as early as midlife and remain invisible to routine imaging tests used to assess bone strength.
The findings suggest a link between Alzheimer’s risk and skeletal health and could help pave the way for earlier detection of both conditions.
Professor Birgit Schilling, a senior author of the study, said: “What makes this finding so striking is that bone quality is being compromised at a molecular level that a standard bone scan simply will not catch.
“APOE4 is quietly disrupting the very cells responsible for keeping bone strong – and it is doing this specifically in females, which mirrors what we see with Alzheimer’s disease risk.”
Doctors have long observed that people with Alzheimer’s suffer higher rates of bone fractures, while osteoporosis in women is known to be one of the earliest predictors of the disease.
Now scientists believe they may have uncovered why.
Researchers led by Dr Charles Schurman carried out a detailed analysis of proteins in aged mouse bone and found that tissue was unusually rich in molecules linked to neurological disease, including those associated with Alzheimer’s.
In particular, long-lived bone cells known as osteocytes showed elevated levels of APOE, with levels twice as high in older female mice compared with younger or male animals.
Further experiments using genetically modified mice revealed that APOE4 had a strong and sex-specific impact on both bone and brain tissue.
The disruption at the protein level was even greater in bone than in the brain.
However, the bone structure itself appeared completely normal under scans.
Instead, the gene interfered with a key maintenance process inside bone cells, preventing them from repairing microscopic channels that keep bones strong and resilient.
When this process breaks down, bones become more fragile even if they look healthy on standard imaging.
These results suggest bone cells could potentially act as early biological warning signs of cognitive decline in women carrying APOE4.
Professor Lisa Ellerby, another senior author, said: “We think targeting these cells may open a new front in preserving bone quality in this population.”
Experts say the findings highlight the need to view the body as an interconnected system rather than treating diseases in isolation.
Dementia, of which Alzheimer’s is the most common form, remains one of the UK’s biggest health challenges.
Around 900,000 people are currently living with the condition, a figure expected to rise to 1.6 million by 2040.
It is already the leading cause of death, responsible for more than 74,000 deaths each year.
Menopause
Study links heart health to fracture risk in postmenopausal women

Postmenopausal women with high cardiovascular risk face almost double the hip fracture risk, a new study has found.
Postmenopausal women face a high risk of bone fractures.
Due to declines in oestrogen levels, which can lead to an increased risk of osteoporosis, even a low-impact fall can result in a serious hip, back or wrist injury.
An estimated one in three women over 50 will experience a fracture due to bone loss in their lifetime.
The study found that heart health may affect fracture risk after menopause, with women at a higher risk of cardiovascular disease more likely to experience hip and other major bone fractures.
The association between cardiovascular disease risk and fractures was also stronger in women under 65, compared with women aged 65 and older.
In the study, published in The Lancet Regional Health – Americas, researchers used the American Heart Association’s recently developed PREVENT score to estimate a patient’s 10-year risk of cardiovascular disease. Women in the study were grouped as low, borderline, intermediate or high risk.
The strongest link was seen with hip fractures. Women in the high cardiovascular risk group had a 93 per cent higher risk of hip fracture than women in the low-risk group.
Women in the intermediate-risk group had a 33 per cent higher risk.
Higher cardiovascular risk was also linked to a greater risk of fractures in weakened bones in major areas such as the hip, spine, forearm or shoulder.
The findings could indicate that the PREVENT score, developed by the AHA in 2024, may be a valuable tool in identifying patients who could benefit from a bone density screening or referral to a bone health specialist.
Given the prevalence of both conditions and the economic burden they impose, reducing risk for both could improve the lives of older adults.
“While previous studies have suggested a link between cardiovascular disease and fracture risk, we were surprised by the magnitude associated with hip fracture risk,” said lead author Rafeka Hossain, a researcher with the Tulane University School of Medicine. “
Both of these conditions are prevalent and costly, and reducing risk for both could improve the lives of older adults.”
The study included data from more than 21,000 women in the Women’s Health Initiative, one of the largest national women’s health studies.
The findings add to growing evidence that heart health and bone health are closely connected.
Researchers say several biological processes may help explain the link, including chronic inflammation, oxidative stress, changes in calcium regulation and reduced blood flow to bone caused by atherosclerosis.
Hormonal changes after menopause, especially declining oestrogen levels, may also raise the risk of both heart disease and bone loss at the same time.
“Many of the same factors that protect your heart, regular physical activity, a balanced diet rich in calcium and vitamin D, not smoking and managing conditions like diabetes and high blood pressure, also help protect your bones,” Hossain said.
“If you’ve been told you have intermediate or high cardiovascular risk, particularly if you are a postmenopausal woman, it may be worthwhile to talk to your doctor about bone health screening, given the many effective treatments available that reduce fracture risk.”
The study found that women in the high-risk group tended to experience fractures sooner than women in the low-risk group.
For hip fractures, the median time to fracture was 15 years in the high-risk group versus nearly 20 years in the low-risk group.
The researchers caution that more work is needed before cardiovascular risk scores are added to standard fracture screening tools.
But they say the findings suggest that women with intermediate or high cardiovascular risk may want to talk with their doctors about bone health, especially after menopause.
“Taking care of your heart and bones should go hand in hand,” Hossain said.
Ageing
Blood test may help guide cancer treatment for older women

A blood test could help guide breast cancer treatment for women aged 70 and over, a small study suggests.
Researchers analysed blood samples from women with oestrogen receptor-positive breast cancer, a common type fuelled by the hormone oestrogen, who were considering endocrine therapy as their main treatment while forgoing surgery and radiation.
Endocrine therapy works by blocking hormones, while the test looks for circulating tumour DNA, or ctDNA, which are tiny fragments of genetic material shed by cancer cells into the bloodstream. Researchers wanted to see whether these fragments could help identify patients unlikely to respond to endocrine therapy alone.
The study, carried out by scientists at UPMC Hillman Cancer Center and the University of Pittsburgh School of Medicine, found that patients whose ctDNA test was negative, either at the start of treatment or after beginning endocrine therapy, were more likely to have stable disease or tumour shrinkage.
That suggested surgery and radiation, which can cause side effects including scarring, chronic swelling, infection and nerve damage, would probably not improve outcomes for this group.
By contrast, patients whose ctDNA remained positive after receiving endocrine therapy were more likely to experience tumour growth while on the medication, suggesting surgery or other treatments may still be needed to achieve tumour control.
The study did not assess how well the treatments themselves worked. Instead, it focused on identifying an early decision window to help doctors judge which patients were less likely to respond to hormone therapy alone.
Priscilla F. McAuliffe, a breast surgical oncologist at UPMC Hillman and associate professor of surgery at the University of Pittsburgh’s School of Medicine, said: “We are learning that not every patient needs the same treatment based simply on their diagnosis, and instead, care should be right-sized for each individual.”
Because ctDNA can be measured through blood tests, patients were able to take part without frequent hospital visits.
Blood samples were often collected from patients’ homes, easing the burden of travel and allowing researchers to enrol patients from UPMC Hillman network oncology sites across the region, not just the main UPMC Hillman site in Shadyside.
The study also included feedback from patients and their caregivers.
When surveyed, more than 80 per cent of patients said ctDNA test results could help them feel better informed about treatment decisions, particularly during the first six to 12 months of care.
Caregivers said supporting loved ones often meant putting caregiving responsibilities ahead of work and other activities.
Based on the findings, the researchers said that, particularly for caregivers, having a monitoring option that can be carried out from home may be an important consideration.
For both patients and caregivers, they stressed the importance of careful patient education and shared decision-making throughout treatment.
The researchers cautioned that the study involved fewer than 50 patients and that the findings are not yet ready for standard practice.
Larger studies are needed before the approach could be used routinely.
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