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Dementia research: What’s exciting the experts?

According to the World Health Organization (WHO), around 50 million people have dementia worldwide. There are about 10 million new cases each year.

By 2030, the WHO estimates that there will be 82 million people with dementia, globally, and by 2050, that figure may reach 152 million. Currently, no treatment can cure dementia.

Dementia research focuses on understanding how the condition works, why it develops, and how it might be treated. Importantly, there is also a focus on how we can improve the lives of people with dementia.

Approaching protein misfolding

“At the center of many types of dementia is protein misfolding, and it is clear that this plays a key role in disease progression,” explained Prof. Louise Serpell, director of Sussex Neuroscience, a community of more than 50 neuroscience research groups at the University of Sussex, in the United Kingdom. 

“Protein misfolding occurs when a normally functional protein, such as tau, changes its shape and aggregates to form long filaments that are deposited in brain tissues. Several types of dementia, including Alzheimer’s disease and Pick’s disease, involve the misfolding of a protein called tau. In Alzheimer’s, these structures are known as neurofibrillary tangles.”

Serpell, a professor of biochemistry, noted that “The misfolding of this protein is an important therapeutic target because of the wide range of diseases that involve tau.”

The key to understanding and combatting protein misfolding and aggregation is identifying a suitable model system that mimics misfolding. Scientists can then use this model to test hypotheses and pharmaceutical approaches. 

Work in Prof. Serpell’s laboratory, in collaboration with the pharmaceutical company TauRx, has identified a protein fragment that forms paired helical filaments that are similar to those formed in the brains of people with Alzheimer’s disease. Using this model, scientists can more easily investigate ways of reversing the misfolding.

Prof. Serpell continued: “Small molecules and antibodies are being developed that can prevent tau aggregation. One of these is known as a ‘tau aggregation inhibitor,’ which was designed by TauRx and has reached phase 3 clinical trials as a monotherapy, offering hope for a disease-modifying treatment.”

Material Citizenship

Dr. Kellyn Lee is a chartered psychologist and research fellow in aging and dementia at the University of Southampton, in the U.K. She uses everyday household items as the focal point of new, innovative training focused on “risk enablement” in care homes.

The aim of this training, called the Material Citizenship Framework Project, is to “educate staff on the importance of objects in everyday life and how to include objects in care assessments and care planning.”

The program grew from Dr. Lee’s Ph.D. research, which found that residents with dementia often move directly from hospitals into care homes, providing little or no opportunity to return home and choose which possessions to bring with them.

Once in care homes, people with dementia are rarely involved in decisions about their possessions; they lack control over what they have and are often discouraged from interacting with things that are important in maintaining their identity.

Dr. Lee explained to Medical News Today, “Material Citizenship goes beyond just looking at the person’s medical needs, but revisits how that person lived their everyday life before they went into a care home, [including] the objects they used in order to carry out certain tasks, and what kind of routines and rituals they do every day that we can help them maintain.”

Losing access to frequently used possessions can cause disempowerment and confusion. To observers, this confusion can sometimes seem like dementia progression.

The following example underlines the importance of objects:

“Judy would say she didn’t recognize herself when looking in the mirror. Care staff believed this was a symptom of dementia; however, it was because her hair was gray, and before she moved to the care home, she dyed it blonde. She also had straight, flat hair, but before moving into the care home, she would use her curling tongs to curl her hair.”

Dr. Lee told MNT that care home staff training sessions have been amazing. “Staff feel valued, and they say that Material Citizenship gives them a safety net — to the point where they say, ‘One of our residents really wanted to polish her own room with a particular polish. Initially, this was seen as unnecessary, the cleaning staff were there to clean. But now we’ve got her the polish she wanted. She polishes her room, and it makes it smell like home.’”

As this work highlights: Understanding the biology behind dementia is urgent, but understanding how to enhance the lives of those currently living with dementia is equally pressing.

Finding ways to enrich the lives of people with dementia is a crucial element of ongoing research. Wavebreak Media/Offset

Sports and dementia

“There has been a lot in the media around sport and dementia risk, but we don’t have enough clear answers, so research is vital for current and former players and their families, [who need] to be provided with the most up-to-date information,” explained Dr. Richard Oakley, head of research at Alzheimer’s Society, in the U.K.

In an ongoing study, Dr. Oakley and colleagues are focusing on rugby players.

“We have provided funding for 50 former elite rugby players to join the PREVENT: RFC study. Run by Prof. Craig Ritchie, at the University of Edinburgh, and Prof. Willie Stewart, at the University of Glasgow, this new study forms part of the large-scale, world-class PREVENT program looking at the early warning signs of dementia.”

“The rugby players are joining 700 participants already enrolled and will undergo brain scans, comprehensive physical health checks, lifestyle questionnaires, and blood tests, among other assessments.”

“By recruiting former elite rugby players, the researchers hope to see whether they show more early warning signs of dementia than the general population and, if so, whether these are associated with greater exposure to injury during the players’ careers.”

– Dr. Richard Oakley

Because the scientists are still exploring how and why dementia develops, studies such as this may provide vital insight into the early stages of the condition.

The value of a HUG

A “HUG is a soft comforter designed to be cuddled by people living with advanced dementia — it has weighted limbs and a simulated heartbeat, as well as the ability to play the person’s favorite music,” Simon Lord, the innovation program manager at Alzheimer’s Society, explained.

A HUG is much more than a cuddly toy, Lord continued, noting that “Research led by Prof. Cathy Treadaway, at Cardiff Metropolitan University, has shown that HUG[s] can improve quality of life and reduce anxiety and agitation for people in the later stages of dementia, providing the comforting sensation of giving and receiving a hug.”

This type of empathic innovation can make a real difference for people with dementia.  

“There is little available to reduce anxiety in people with advanced dementia. Such a simple product can make a huge difference to someone’s well-being, especially after the extremely damaging side effects of lockdown — long periods of isolation and a loss of social interaction and the comfort of human touch.”

– Simon Lord

Diabetes drug for Alzheimer’s?

Dr. Oakley, of Alzheimer’s Society, is also excited about another ongoing study funded by the organization. This involves the diabetes drug metformin (Glucophage). He told MNT:

Dr. Teresa Niccoli, at University College London, in the U.K., […] is looking into metformin, a drug for type 2 diabetes, which has shown promise in some studies for improving symptoms of Alzheimer’s disease.”

“The improvement in symptoms has been observed in a small-scale clinical trial for Alzheimer’s disease, as well as in fruit fly studies.”

However, as is often the case with medical research, all that glitters is not gold. Dr. Oakley explained: “Metformin treatment has also been shown to increase the buildup of amyloid deposits, which are known to be associated with Alzheimer’s disease. It’s clear that we need to better understand how metformin works and whether it could be a potential treatment for Alzheimer’s.”

“The researchers are using fly models of Alzheimer’s disease to identify genes that affect metformin treatment without the buildup of amyloid deposits.”

In one study, for instance, Dr. Niccoli and colleagues used an adult-onset fruit fly model that mimicked Alzheimer’s. They found that metformin rescued the fly’s nervous system from some of the toxic effects. They also identified that the suppression of a protein called Grp78 was important in this activity. The authors conclude that Grp78 could be “a novel therapeutic target for the treatment of Alzheimer’s disease.”

The next steps, Dr. Oakley noted, are to “look at the genes in human brain cells that are affected by Alzheimer’s disease to see if similar effects are observed.”

Dr. Oakley concludes: “Repurposing drugs that are already used is a great place to start. We can learn how these drugs work and then develop more targeted treatments without unwanted side effects.”

The role of blood supply

“For me, the most exciting avenue of research into dementia is the interface between the brain’s blood supply and the emergence of neurodegeneration and cognitive decline,” said Dr. Catherine Hall, a senior lecturer in psychology at the University of Sussex.

“We’ve known for a long time that dementia and cardiovascular disease share risk factors. [J. C.] de la Torre put forward the vascular hypothesis of Alzheimer’s disease 30 years ago after connecting damage to the small blood vessels in the brain with the decreased blood flow and impaired energy use seen in dementia patients.” 

However, Dr. Hall explained, scientists only fairly recently discovered “that decreased blood flow happens well before any of the classic Alzheimer’s disease pathology,” such as beta-amyloid buildup, tau tangles, and cognitive decline.

This implies that decreased blood flow “might actually cause dementia to occur.” 

Dr. Hall described how this reduction might lead to Alzheimer’s: “Toxic proteins, such as beta-amyloid, build up more in the low-oxygen conditions that are created when the blood supply is lowered.” Also, “These proteins constrict blood vessels to further worsen the blood supply, creating a vicious cycle that could lead to neuronal damage and cognitive decline.”

However, questions remain. “We don’t know how the brain switches from unhealthy but coping to undergoing neurodegeneration.”

Factors that might be involved are age, infection, trauma, and lifestyle factors, including an unhealthy diet and lack of exercise.

Although more work is needed, Dr. Hall believes that “Probably, these risk factors gradually impair how blood vessels work in our brain until, suddenly, our neurons stop working.”

“My lab’s recent work shows that the brain’s memory center, the hippocampus, normally has much lower blood oxygen levels than the sensory cortex and is less able to regulate its blood supply by dilating blood vessels.”

Based on this finding, Dr. Hall and her team predict that, while the sensory cortex might deal with alterations to blood flow more easily, the hippocampus is “at a tipping point, where a small nudge will reduce brain oxygen to levels that stop neurons working so well. This might explain why memory problems are some of the first symptoms of Alzheimer’s disease.”

Dr. Hall explained that scientists need to carry out “more research to test the prediction that a small decrease in blood flow is catastrophic for the hippocampus and to understand the exact pathways that link a decrease in flow with classic Alzheimer’s disease damage, [in order] to discover new treatments.”

Until then, she recommends that we, “Keep our hearts and blood vessels healthy, with a good diet and exercise, to keep the blood flowing properly to the brain.”

Reaching the end

“In a society aging with dementia, research is essential to establish the causes, therapies, medication, and cures, which can support families affected by the condition,” said Dr. Karen Harrison Dening, head of research and publications at Dementia UK. She explained to MNT:

“At Dementia UK, we know there are thousands of people living with dementia right now. As such, more focused research into dementia care, which acknowledges needs and values individuals’ experiences, can provide access to high-quality support, from diagnosis through to bereavement.”

– Dr. Karen Harrison Dening

“In line with this, Dementia UK is partnering with the University of Kent, in the U.K., to uncover what makes a good death in dementia care.”

“The project seeks to inform policy development around death and dying in dementia, which is right now predominantly seen through a clinical lens rather than a person-centered one. Hearing from people with a diagnosis of dementia is a key aim of this study.”

The take-home message

Scientists are working tirelessly to find better ways to treat and manage dementia, but there is still a long road ahead. Dr. Oakley, from Alzheimer’s Society, told us:

“Decades of underfunding in dementia research means that it can be difficult to make progress. The U.K. government must keep their commitment to double dementia research funding. With financial support, research will beat dementia.”

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