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Women taking HRT may be at greater risk of dementia



Women taking hormone replacement therapy (HRT) to relieve menopausal symptoms may be at greater risk of developing dementia and Alzheimer’s disease, a new study suggests.

The research conducted in Denmark involving more than 60,000 women and published in the latest issue of The British Medical Journal, showed that those using HRT treatments – which include tablets containing oestrogen only, or a combination of oestrogen and progestogen, as well as skin patches, gels and creams – were 24% more likely to develop all-cause dementia and Alzheimer’s in later life.

An increased risk was seen not only in long-term HRT users but also in those taking the treatment short-term around the age of menopause – defined as 55 years or younger, as is currently recommended.

These latest findings appear to contradict other studies – including one conducted by the Mass General Brigham Hospital based in Boston, Massachusetts, published in April this year –  that suggested HRT actually protects against cognitive decline if it’s started near the age of diagnosis.

That study found that women who began HRT treatment five or six years after the start of the menopause had higher levels of two key proteins involved in dementia, tau and beta-amyloid.

The researchers in that study admitted more investigations were needed to determine how the menopause and HRT affect the brain. But their early findings suggested starting HRT as soon as the first menopausal symptoms appear may be better not only for brain health but in helping reduce heart disease and other medical symptoms associated with the change of life. 

A number of experts have adopted a circumspect view on this latest Danish research, especially as the team behind it couldn’t distinguish the reasons HRT was being prescribed in the first place from the early symptoms of dementia.

Many menopausal symptoms, such as brain fog, sleep disturbance, confusion and memory problems, can lead some to fear they are showing the early signs of dementia or Alzheimer’s.

Conversely, for some of the women in the study, the symptoms being treated by HRT may actually have been a sign of early neurological changes that would have developed into dementia.

Dr Sarah-Naomi James, senior research Fellow at the MRC Unit for Lifelong Health and Ageing at University College London, said: “The editorial seems very fair – the study has strengths in utilising nationwide data it has available and their effort to try to differentiate between different types and duration of HRT use is admirable, well-needed and seems fairly robust.

“However, the study has fundamental limitations in its ability to interpret and understand the true underlying causal pathways of the observed association, as both the exposure (why you would be prescribed HRT in the first place, and why you would be prescribed certain types and duration of medication use) and the outcome (dementia diagnosis) have many things in common that influence them, and so this association may be artificial.

“For example, changes in sleep or mood are very common symptoms of menopause and reasons to seek out HRT; meanwhile we are starting to understand that sleep and mood may play an important role in the expression and progression of dementia.

“The best way to understand whether HRT medication itself causes dementia comes from clinical trials, and to date, there is not enough evidence to support a direct link from the medication itself, and this new study alone should not change practice.”

Dr Amanda Heslegrave, senior research fellow at the UK Dementia Research Institute, added: “I don’t believe you can suggest a causal link from this data. It is known that many women who seek HRT at or around menopause do so because of concerns around memory and cognition, potentially confounding data.

“There is research that suggests HRT can be protective with respect to dementia, also other research that the paper cites, that HRT is associated with dementia – this suggests to me that we really don’t know the whole story and targeted research is required.”

One such piece of research showing a link between long-term use of HRT and the development of dementia was the landmark Women’s Health Initiative Memory Study, the largest clinical trial on this topic.

But the effect of short-term use of menopausal hormone therapy around the age of menopause, as is currently recommended, remains to be fully explored. The effect of different treatment regimens on risk of dementia is also uncertain.

To try and fill these knowledge gaps, the researchers in Denmark assessed the association between the use of combined oestrogen and progestin (synthetic progestogen) therapy and the development of dementia according to type of hormone treatment, duration of use, and age at use.

Drawing on national registry data, they identified 5,589 cases of dementia and 55,890 age matched dementia-free controls between 2000 and 2018 from a population of all Danish women aged between 50 and 60 years at the turn of the century with no history of dementia and no underlying reason preventing them from using HRT.

Other relevant factors including education, income, hypertension, diabetes, and thyroid disease were also taken into account.

The average age at diagnosis was 70 years. Before a diagnosis, 1,782 (32%) cases and 16,154 (29%) controls had received oestrogen-progestin therapy from an average age of 53 years. The average duration of use was 3.8 years for cases and 3.6 years for controls.

The results showed that, compared with people who had never used HRT, those who had received oestrogen-progestin therapy had a 24% increased rate of developing all cause dementia and Alzheimer’s disease, even in women who received treatment at the age of 55 years or younger.

The rates were higher with longer use, ranging from 21% for one year or less to 74% for more than 12 years of use.

The increased rate of dementia was similar between continuous (oestrogen and progestin taken daily) and cyclic (daily oestrogen with progestin taken 10-14 days a month) treatment regimens.

Use of progestin and vaginal oestrogen only therapies were not associated with the development of dementia.

The researchers admitted that this is an observational study, so couldn’t establish cause, and that they were not able to isolate vascular dementia from other types of the disease or distinguish between tablets and alternative ways to take hormone therapy, such as patches.

What’s more, they couldn’t rule out the possibility that women using hormone therapy had a predisposition to both menopausal vasomotor symptoms, such as hot flushes and night sweats, and dementia.

However, this was a large study based on high quality treatment data with long follow-up time.

The authors were also able to investigate cyclic and continuous hormone formulations separately, as well as age of starting HRT and the length of treatment, allowing them to analyse an important overlooked aspect of this topic – namely the dementia risk in short-term users of HRT around the age of menopause onset, as recommended in treatment guidelines.

As such, they concluded: “Further studies are warranted to determine whether these findings represent an actual effect of menopausal hormone therapy on dementia risk, or whether they reflect an underlying predisposition in women in need of these treatments.”


Tai chi outperforms conventional exercise for seniors



New findings from 12 studies involving 2,901 participants have demonstrated that tai chi outperforms conventional exercise in improving mobility and balance in seniors.

While tai chi is understood to be beneficial for functional mobility and balance in older adults, such benefits are not well understood due to large variance in research study protocols and observations.

This new review and analysis has now shown that tai chi can induce greater improvement in functional mobility and balance in relatively healthy older adults compared to conventional exercise.

The findings showed the following performance results:

  • The time to complete 50-foot walking was 1.84 seconds faster. 
  • The time to maintain a one-leg stance was 6 seconds longer when eyes were open and 1.65 seconds longer when eyes were closed. 
  • Individuals improved their timed-up-and-go test performance by 0.18 points, indicating quicker standing, walking, and sitting.
  • Individuals taking the functional reach test showed significant improvement with a standardised mean difference of 0.7, suggesting a noteworthy positive impact on the ability to reach and perform daily activities.

Secondary analyses revealed that the use of tai chi with relatively short duration of less than 20 weeks, low total time of less than 24 total hours, and/or focusing on the Yang-style of this ancient form of Chinese martial arts were particularly beneficial for functional mobility and balance as compared to conventional exercise.

“This systematic literature review and meta-analysis are exciting because they provide strong evidence that tai chi is a more efficient strategy to improve functional mobility and balance in relatively healthy older adults, as compared to conventional exercise,” said Brad Manor, Ph.D., director of the Mobility and Falls Program at Hebrew SeniorLife’s Hinda and Arthur Marcus Institute for Aging Research, and associate professor of medicine, Harvard Medical School and Beth Israel Deaconess Medical Center.

“This research suggests that tai chi should be carefully considered in future studies and routines of rehabilitative programs for balance and mobility in older adults,” said Bao Dapeng, professor at Beijing Sport University.

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New standards for biomarkers of ageing



A paper has put forward a new framework for standardising the development and validation of biomarkers of ageing to better predict longevity and quality of life.

Led by Harvard researchers, the team has zeroed in on biomarkers of ageing using omic data from population-based studies. 

The team included ageing and longevity expert Alex Zhavoronkov, PhD, founder and CEO of AI-driven drug discovery company Insilico Medicine, and the findings appeared in Nature Medicine

Ageing is associated with a number of biological changes including increased molecular and cellular damage, however, researchers do not yet have a standardised means to evaluate and validate biomarkers related to ageing. 

In order to create those standards as well as actionable clinical tools, the team analysed population-based cohort studies built on omic data (data related to biological molecules which can include proteomics, transcriptomics, genomics, and epigenomics) of blood-based biomarkers of ageing. The researchers then compared the predictive strength of different biomarkers, including study design and data collection approaches, and looked at how these biomarkers presented in different populations. 

In order to better assess the impact of ageing using biomarkers, the researchers found that clinicians needed to expand their focus to consider not only mortality as an outcome, but also how biomarkers of aging are associated with numerous other health outcomes, including functional decline, frailty, chronic disease, and disability. They also call for the standardisation of omic data to improve reliability. 

“Omics and biomarkers harmonisation efforts, such as the Biolearn project, are instrumental in validation of biomarkers of aging” said co-first author Mahdi Moqri, PhD, of the Division of Genetics. 

Biolearn is an open-source project for biomarkers of aging and is helping to harmonise existing ageing biomarkers, unify public datasets, and provide computational methodologies.

The team also emphasised the importance of continued collaborations among research groups on “large-scale, longitudinal studies that can track long-term physiological changes and responses to therapeutics in diverse populations”, and that further work is required to understand how implementation of biomarker evaluation in clinical trials might improve patient quality of life and survival.

“If we hope to have clinical trials for interventions that extend healthy lifespan in humans, we need reliable, validated biomarkers of ageing,” said co-first author Jesse Poganik, PhD, of the Division of Genetics. 

“We hope that our framework will help prioritise the most promising biomarkers and provide health care providers with clinically valuable and actionable tools.”

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Healthy aging research to receive $115 million



Global non-profit Hevolution Foundation has announced $115 million in funding that makes up 49 new awards under its Geroscience Research Opportunities (HF-GRO) programme.  

As part of Hevolution’s mission to catalyse the healthspan scientific ecosystem and drive transformative breakthroughs in healthy aging, HF-GRO is funding promising pre-clinical research in aging biology and geroscience. 

Through this first wave of HF-GRO awards, Hevolution will invest up to $115 million in this first cohort of 49 selected projects over the next five years. Its second call for proposals under HF-GRO will be announced later this year, offering an additional $115 million to address the significant funding gaps in aging research.  

Dr. Felipe Sierra, Hevolution’s Chief Scientific Officer stated: “These 49 important research projects represent a significant step forward in deepening our understanding of healthy aging. Hevolution’s prime objective is to mobilise greater investment around uncovering the foundational mechanisms behind biological aging. 

“We are steadfast in our belief that by examining the root causes of aging, rather than solely focusing on its associated diseases, we can usher in a brighter future for humanity.” 

HF-GRO awardees include researchers at prestigious institutions across the United States, Canada, and Europe, including the U.S. National Institute on Aging, Brigham and Women’s Hospital, the Buck Institute, the Mayo Clinic, New York University, and the University of California San Francisco, among many others. 

The American Federation for Aging Research is providing programmatic support for the HF-GRO program, with grantees selected through a rigorous two-stage peer-review process involving 100 experts in aging biology and geroscience. 

Dr Berenice Benayoun, an HF-GRO grant recipient at the University of Southern California, stated: “I am extremely honored and excited that Hevolution selected our project for funding. This is a project close to my heart, which aims at understanding why and how the female and male innate immune aging differs. 

“This funding will support us as we start laying the foundation for a lasting improvement of women’s health throughout aging.” 

To date, Hevolution has committed approximately $250 million to transform the healthy aging sector, including the $40 million for specialised research and development in healthspan science recently announced at Hevolution’s Global Healthspan Summit. 

Hevolution is ramping up its investments to enable healthier aging for all and is now the second largest funder of aging biology research worldwide.  

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