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Women taking HRT may be at greater risk of dementia

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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.”

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On a mission to show that hearing loss is not inevitable

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The world’s largest investigation into the effectiveness of hearing training kicks off this week – as part of a movement to prove that hearing loss is not an inevitable part of ageing.

The research project aims to attract a minimum of 10,000 participants to better understand how hearing training impacts auditory processing skills like speech comprehension and the ability to locate where sounds are coming from.

Researchers are interested in the impact of hearing training on users who start training with different hearing ability levels, as well as training adherence in groups with different attitudes to smartphone technology.

Their aim is to find new ways to deliver and improve auditory training at scale and for a wider range of hearing skills; and to measure factors which influence training engagement.

The research is led by health tech firm Eargym. Co-founder Andy Shanks says:  Contrary to popular belief, hearing loss is not an inevitable consequence of ageing. We can take steps to improve and protect our hearing throughout our lives, yet preventative measures like hearing training have traditionally been under-researched.

“Our data shows the transformative impact hearing training can have on our ability to process sounds. Now, we want to deepen and widen our research and use our platform to make hearing training even more effective and accessible. Imagine improving and maintaining your hearing by up to 20% or more: it could make a big difference to the lives of so many people.”

The games on the Eargym app include a “busy barista” exercise, where users must discern speech over a cafe’s bustling background noise; and a “sound seeking” exercise, where users make their way through forests, jungles and oceans to locate the sources of different sounds. Each game is designed to be immersive and to help users practise specific auditory processing skills regularly.

Eargym was set up by former NHS CEO Amanda Philpott and DJ Andy Shanks in 2020, after they were both diagnosed with hearing loss. Amanda has moderate age related hearing loss, whilst Andy has “notch” or noise-induced hearing loss due to DJ-ing. Both found hearing loss isolating and it impacted their ability to socialise and communicate. They created eargym to empower others to better understand their hearing health and take proactive steps to protect it.

Hearing loss currently affects 18 million adults in the UK, with around one billion young people at risk of developing hearing loss due to increased use of headphones. Hearing loss is closely associated with increased dementia risk. Despite this, people wait an average ten years before seeking help for hearing loss.

Eargym plans to publish the findings of its research in early 2025.

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Interview: Exploring electrical stimulation for Parkinson’s disease

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The STEPS II study is investigating functional electrical stimulation (FES) in people with Parkinson’s disease to help improve their walking. Dr Paul Taylor, co-founder and Clinical Director of Odstock Medical Ltd (OML), spoke to Agetech World to tell us more.

Bradykinesia – slowness of movement which can lead to difficulty walking – affects many people living with Parkinson’s disease. The symptom can cause Parkinson’s patients to walk or move slowly, increasing the risk of falls, leading to a reduced quality of life and an increased dependence on others. 

Funded by the National Institute for Health and Care Research, sponsored by Salisbury NHS Foundation Trust, and managed by the University of Plymouth’s Peninsula Clinical Trials Unit, the STEPS II study is exploring the use of an FES device in Parkinson’s patients to help improve bradykinesia. 

The FES device, which has been pioneered by Salisbury researchers as a drop foot treatment for stroke and MS patients, is attached to the patient’s leg and produces small electrical impulses that improve movement.

“If you have Bradykinesia you’re moving slowly. The predominant treatment for Parkinson’s is medication and these can be very effective, but they have the problem of not working all the time,” explains Taylor, co-founder of Odstock Medical Ltd, a company owned by Salisbury NHS Foundation Trust.

”The effects of the drugs will wear off and after a period of time they become less effective, so, there’s a need for improvement.”

Taylor explains that deep brain stimulators are currently available, however, they are very invasive, expensive and can be risky. 

“We’re trying to do something which is a bit simpler and cheaper, which may possibly be able to help people at an earlier stage of Parkinson’s,” Taylor says.

“We’re stimulating the common peroneal nerve, which is the nerve that goes down the leg to the muscles, using a device called a drop foot stimulator. The device is commonly used for stroke and multiple sclerosis.”

A small feasibility study has already been conducted, which showed that FES can help patients walk faster and reduce some symptoms of Parkinson’s. 

In the STEPS II study, researchers hope to confirm the long-term effects of FES on walking speed and daily life with 234 participants at sites across Salisbury, Birmingham, Prestwick, Leeds, Swansea and Carlisle.

Taylor continues: “Our original idea was that we could use electrical stimulation to overcome freezing – which is the effect where people with Parkinson’s will stop walking, particularly when they come to doorways or very narrow areas. It’s to do with the processing of information from the outside world. 

“We wanted to see if we could use electrical stimulation to overcome that freezing and, to a certain extent, we did find that is the case for some patients, but more commonly and with a greater number of patients FES affected bradykinesia – speeding up their movement and helping with more effective walking.”

For the STEPS II study, participants will be randomised into a care as normal group, or a care as normal plus FES group. They will use the stimulator if they are in the FES group for 18 weeks, then the stimulator is taken away, with patients followed up one month later to see if the effects are continued.

Measurements of walking speed and movement will be analysed, along with sensory perception, balance, coordination, muscle strength, as well as secondary effects such as how the device impacts daily living and quality of life.

OML has established clinics around the country with trained therapists where the device will be used if the study is successful. 

“There’s a network of clinics already experienced in using the treatment so we plan to reach those clinics to include Parkinson’s patients in their cohorts,” says Taylor. “Then we’ll work with our contacts to see if we can get it overseas as well.”

OML is currently recruiting participants for the study, to find out more please visit: https://www.plymouth.ac.uk/research/penctu/steps-2 

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Quit Googling to stave off dementia onset, expert urges

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Resisting the temptation to search the web for information that could otherwise be recalled be exercising your brain could help to reduce the risk of dementia.

That is according to Canadian academic Professor Mohamed I. Elmasry who believes simple daily habits such as afternoon naps, memory ‘workouts’ and not reaching for a smartphone can increase the odds of healthy aging.

His new book, iMind: Artificial and Real Intelligence, says the focus has shifted too far away from RI (natural, or real) intelligence in favour of AI (machine, or artificial) intelligence. Elmasry instead calls us to nurture our human mind which, like smartphones, has ‘hardware’, ‘software’ and ‘apps’ but is many times more powerful – and will last much longer with the right care.

Professor Elmasry, an internationally recognised expert in microchip design and AI, was inspired to write the book after the death of his brother-in-law from Alzheimer’s and others very close to him, including his mother, from other forms of dementia.

Although he says that smart devices are ‘getting smarter all the time’, he argues in iMind that none comes close to ‘duplicating the capacity, storage, longevity, energy efficiency, or self-healing capabilities of the original human brain-mind’.

He writes that: “The useful life expectancy for current smartphones is around 10 years, while a healthy brain-mind inside a healthy human body can live for 100 years or longer.

“Your brain-mind is the highest-value asset you have, or will ever have. Increase its potential and longevity by caring for it early in life, keeping it and your body healthy so it can continue to develop.

“Humans can intentionally develop and test their memories by playing ‘brain games,’ or performing daily brain exercises. You can’t exercise your smartphone’s memory to make it last longer or encourage it to perform at a higher level.”

In iMind: Artificial and Real Intelligence Professor Elmasry shares an anecdote about his grandchildren having to use the search engine on their smartphones to name Cuba’s capital—they had just spent a week in the country with their parents.

The story illustrates how young people have come to rely on AI smartphone apps instead of using their real intelligence (RI), he says, adding: “A healthy memory goes hand-in-hand with real intelligence. Our memory simply can’t reach its full potential without RI.”

Published by Routledge, iMind: Artificial and Real Intelligence includes extensive background on the history of microchip design, machine learning and AI and their role in smartphones and other technology.

The book also explains how both AI and human intelligence really work, and how brain function links the mind and memory. It compares the human mind and brain function with that of smartphones, ChatGPT and other AI-based systems.

Drawing on comprehensive existing research, iMind aims to narrow the knowledge gap between real and artificial intelligence, to address the current controversy around AI, and to inspire researchers to find new treatments for Alzheimer’s, other neurodegenerative conditions and cancer.

It argues that current or even planned AI cannot match the capabilities of the human brain-mind for speed, accuracy, storage capacity and other functions. Healthy aging, Professor Elmasry notes, is as important as climate change but doesn’t attract a fraction of the publicity.

He calls for policymakers to adopt a series of key reforms to promote healthy aging. Among such changes, he suggests that bingo halls could transition from their sedentary entertainment function to become active and stimulating learning centers.

As well as napping to refresh our memories and other brain and body functions, he also outlines a series of practical tips to boost brain power and enhance our RI (Real Intelligence).

These include building up ‘associative’ memory – the brain’s ‘dictionary of meaning’ where it attaches new information to what it already knows. Try reading a book aloud, using all of your senses instead of going on autopilot and turning daily encounters into fully-lived experiences.

Other techniques include integrating a day for true rest into the week, reviewing your lifestyle as early as your 20s or 30s, adopting a healthy diet, and eliminating or radically moderating alcohol consumption to reduce the risk of dementia.

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