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Deep brain stimulation eases cognitive decline in Alzheimer’s mice

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Alzheimer’s experts have given a cautious welcome to an innovative study that showed an easing of cognitive impairment in rodents through the use of deep brain stimulation.

An estimated 32 million people globally suffer from Alzheimer’s disease, for which there is currently no cure.

The most common form of dementia, it is a progressive, life-limiting illness caused by a build-up of proteins in the brain that slowly destroys the memory, thinking, behaviour, and social skills, eventually leaving the sufferer unable to carry out even the simplest of tasks.

But researchers from the University of North Carolina at Chapel Hill have demonstrated that deep brain stimulation of new neurons can help to restore both cognitive and noncognitive functions in mouse models of Alzheimer’s disease.

However, leading Alzheimer’s specialists, whilst welcoming any new study that helps to “unravel the complexities” of such a devastating disease, have pointed to the results being in mice rather than humans.

Dr Sara Imarisio, Head of Strategic Initiatives at Alzheimer’s Research UK, said: “It’s important to note that these results are in mice, and there are differences between mouse and human brains. And while these findings provide a promising lead for investigating potential new approaches for treating Alzheimer’s in humans, it’s a very long way from practical application.

“Nevertheless, studies like these are essential to unravel the complexities of Alzheimer’s, and bring us closer to ways to effectively treat, and even cure, the disease,” she added.

Prof Malcolm Macleod, Professor of Neurology and Translational Neuroscience at the University of Edinburgh, said the study was potentially of interest, but pointed to some problems with the methods used.

“Specifically, on the presentation, the title says that the intervention ‘restores cognitive and affective function in Alzheimer’s disease’, but this is to overstate things.

“Mice do not get Alzheimer’s, although scientists can model some of the features in certain animal models, as presented here. But these do not capture the whole story of what Alzheimer’s does to humans, and we know of many interventions which appear to improve outcome in these (imperfect) animal models, but which have no effect in humans.”

Reporting in the journal Cell Stem Cell, the team detailed how they utilised the mice to demonstrate a process called adult hippocampus neurogenesis (AHN), through which neurons are made in adulthood.

The neurons were modified by deep brain stimulation of the supramammillary nucleus (SuM), which is located in the hypothalamus, a gland which controls many bodily functions such as heart rate, hunger, body temperature, sleep and emotions.

A neurological process, deep brain stimulation involves planting electrodes into certain parts of the brain and connecting them by wires to a pacemaker-like device placed under the skin in the chest area.

The electrodes create electrical impulses that override abnormal signals that could cause neurological problems. It is a type of surgery that is already used to treat Parkinson’s disease to help improve tremors, stiffness, and movement issues, as well as epilepsy, dystonia and obsessive compulsive disorder.

Senior report author, Juan Yong, as associate professor at the University of North Carolina at Chapel Hill, said: “We were surprised to find that activating only a small population of adult-born new neurons was enough to make a significant contribution to these brain functions.

“We are eager to find out the mechanisms that underlie these beneficial effects.”

The study used two distinct mouse models of Alzheimer’s disease. The investigators used optogenetics to stimulate the SuM and enhance AHN in Alzheimer’s mice.

Earlier research conducted by the team had shown that stimulation of the SuM could increase the production of new neurons and improve their qualities in normal adult mice.

In the new study, the investigators showed that this strategy was also effective in the Alzheimer’s mice, leading to the generation of new neurons that made better connections with other areas of the brain.

However, having more improved new neurons is not enough to enhance memory and mood. Behavioural improvement in Alzheimer’s mice was seen only when these improved new neurons were activated by chemogenetics, a method of using synthetic designer drugs to control and investigate intracellular signalling pathways.

The researchers used memory tests as well as established assessments to look for anxiety and depression-like behaviour to verify these improvements. The findings suggested that multi-level enhancement of new neurons – including increased numbers, properties, and activity – is needed for behavioural restoration in Alzheimer’s brains.

Juan Yong said: “It was striking that multilevel enhancement of such a small number of adult-born new neurons made such a profound functional contribution to the animals’ diseased brains.”

But Prof Macleod pointed out the number of animals used was “fairly low, which again brings the conclusions into question. They say they based the numbers of animals used on previous experiments, but we know that experiments in the neurosciences are substantially under-powered (ie too small reliably to detect the effects they report), and so doing it this way because that’s how we have always done it is problematic.”

 

 

 

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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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