̽��ֱ�� of Cambridge - dementia

AI can be good for our health and wellbeing

cjb250 — Mon, 07 Apr 2025 08:00:08 +0000

Cambridge researchers are looking at ways that AI can transform everything from drug discovery to Alzheimer's diagnoses to GP consultations.

Dementia patients and their carers to be asked about direction of drug research

cjb250 — Wed, 19 Mar 2025 07:00:07 +0000

Today sees the launch of the POrtal for Patient and Public Engagement in Dementia Research (POPPED) website, where anyone can give their feedback on dementia research projects.

Dementia affects 50 million people worldwide and 1 million people in the UK. Current treatments are limited, but research has led to some significant recent advances. For example, the first drugs which slow down the disease are now licensed in the UK and potential dementia blood tests are being trialled.

Scientists are also turning to existing drugs to see if they may be repurposed to treat dementia. As the safety profile of these drugs is already known, the move to clinical trials can be accelerated significantly. Researchers want to ask members of the public which drugs they would like to see prioritised for these clinical trials.

Dr Ben Underwood, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, said: “One thing that always improves research into medical conditions is the involvement of people with experience of them – in many respects, you are the experts, rather than us.

“As dementia is common, almost everyone has some experience of it, either through family, friends, work or meeting people with dementia in general life. It’s a problem across society and we want a wide range of opinions for the best way to tackle it.”

Dr Underwood has teamed up with Linda Pointon, a Programme Manager at the Department of Psychiatry, to create a website where everyone can give their feedback on dementia research projects. Linda herself has experience of caring for her mother-in-law, who had frontotemporal dementia and passed away in 2020.

Linda said: “We’re launching our website because we want as many people as possible to share their views and help us guide the direction of our research. It’s a great opportunity for all of us who have been affected by dementia, either directly or caring for a friend or relative, to help researchers understand what aspects of these potential treatments are important and meaningful, both in terms of benefits and side-effects.”

̽��ֱ��information collected by the POPPED team will be used to help inform AD-SMART, a trial to be led by Imperial College London, which will test several existing drugs alongside a placebo to quickly determine if any can slow early Alzheimer’s progression.

Dr Underwood added: “Instead of asking a few people what might be helpful, our website gives us the opportunity to ask thousands of people. ̽��ֱ��more people who use it, the more powerful it will be, so I’d encourage everyone to visit the site and tell us what they think. We can use it to work together to beat dementia, a condition whose effects I see in my clinic every day.”

Cambridge researchers are seeking the views of people with lived experience of dementia – patients and their friends and families – on which existing drugs should be repurposed for clinical trials to see whether they can slow or halt the progress of dementia.

One thing that always improves research into medical conditions is the involvement of people with experience of them – in many ways, they are the experts, not us

Ben Underwood

Toa55 (Getty Images)

Elderly woman putting pills into pill box for the week - stock photo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Cambridge researcher aims to unlock new dementia treatments with nationwide blood test trial

sb726 — Thu, 13 Feb 2025 07:50:03 +0000

A simple blood test is being rolled out across the UK as part of a new study to detect early signs of dementia decades before it develops and help identify treatments.

Antibiotics, vaccinations and anti-inflammatory medication linked to reduced risk of dementia

cjb250 — Tue, 21 Jan 2025 12:00:03 +0000

̽��ֱ��study, led by researchers from the universities of Cambridge and Exeter, identified several drugs already licensed and in use that have the potential to be repurposed to treat dementia.

Dementia is a leading cause of death in the UK and can lead to profound distress in the individual and among those caring for them. It has been estimated to have a worldwide economic cost in excess of US$1 trillion dollars.

Despite intensive efforts, progress in identifying drugs that can slow or even prevent dementia has been disappointing. Until recently, dementia drugs were effective only for symptoms and have a modest effect. Recently, lecanemab and donanemab have been shown to reduce the build-up in the brain of amyloid plaques – a key characteristic of Alzheimer’s disease – and to slow down progression of the disease, but the National Institute for Health and Care Excellence (NICE) concluded that the benefits were insufficient to justify approval for use within the NHS.

Scientists are increasingly turning to existing drugs to see if they may be repurposed to treat dementia. As the safety profile of these drugs is already known, the move to clinical trials can be accelerated significantly.

Dr Ben Underwood, from the Department of Psychiatry at the ̽��ֱ�� of Cambridge and Cambridgeshire and Peterborough NHS Foundation Trust, said: “We urgently need new treatments to slow the progress of dementia, if not to prevent it. If we can find drugs that are already licensed for other conditions, then we can get them into trials and – crucially – may be able to make them available to patients much, much faster than we could do for an entirely new drug. ̽��ֱ��fact they are already available is likely to reduce cost and therefore make them more likely to be approved for use in the NHS.”

In a study published today in Alzheimer’s and Dementia: Translational Research & Clinical Interventions, Dr Underwood, together with Dr Ilianna Lourida from the ̽��ֱ�� of Exeter, led a systematic review of existing scientific literature to look for evidence of prescription drugs that altered the risk of dementia. Systematic reviews allow researchers to pool several studies where evidence may be weak, or even contradictory, to arrive at more robust conclusions.

In total, the team examined 14 studies that used large clinical datasets and medical records, capturing data from more than 130 million individuals and 1 million dementia cases. Although they found a lack of consistency between studies in identifying individual drugs that affect the risk of dementia, they identified several drug classes associated with altered risk.

One unexpected finding was an association between antibiotics, antivirals and vaccines, and a reduced risk of dementia. This finding supports the hypothesis that common dementias may be triggered by viral or bacterial infections, and supports recent interest in vaccines, such as the BCG vaccine for tuberculosis, and decreased risk of dementia.

Anti-inflammatory drugs such as ibuprofen were also found to be associated with reduced risk. Inflammation is increasingly being seen to be a significant contributor to a wide range of diseases, and its role in dementia is supported by the fact that some genes that increase the risk of dementia are part of inflammatory pathways.

̽��ֱ��team found conflicting evidence for several classes of drugs, with some blood pressure medications and anti-depressants and, to a lesser extent, diabetes medication associated with a decreased risk of dementia and others associated with increased risk.

Dr Ilianna Lourida from the National Institute for Health and Care Research Applied Research Collaboration South West Peninsula (PenARC), ̽��ֱ�� of Exeter, said: “Because a particular drug is associated with an altered risk of dementia, it doesn’t necessarily mean that it causes or indeed helps in dementia. We know that diabetes increases your risk of dementia, for example, so anyone on medication to manage their glucose levels would naturally also be at a higher risk of dementia – but that doesn’t mean the drug increases your risk.

“It’s important to remember that all drugs have benefits and risks. You should never change your medicine without discussing this first with your doctor, and you should speak to them if you have any concerns.”

̽��ֱ��conflicting evidence may also reflect differences in how particular studies were conducted and how data was collected, as well as the fact that different medications even within the same class often target different biological mechanisms.

̽��ֱ��UK government is supporting the development of an Alzheimer’s trial platform to evaluate drugs rapidly and efficiently, including repurposed drugs currently used for other conditions.

“Pooling these massive health data sets provides one source of evidence which we can use to help us focus on which drugs we should try first,” said Dr Underwood. “We’re hopeful this will mean we can find some much-needed new treatments for dementia and speed up the process of getting them to patients.”

Reference
Underwood, BU & Lourida, I et al. Data-driven discovery of associations between prescribed drugs and dementia risk: A systematic review. Alz & Dem; 21 Jan 2025; DOI: 10.1002/trc2.70037

Antibiotics, antivirals, vaccinations and anti-inflammatory medication are associated with reduced risk of dementia, according to new research that looked at health data from over 130 million individuals.

We urgently need new treatments to slow the progress of dementia, if not to prevent it. If we can find drugs that are already licensed for other conditions, then we can get them into trials much faster than we could do for an entirely new drug

Ben Underwood

Andrzej Rostek (Getty Images)

Elderly Woman's Hands and Orange Pills

Yes

Glaucoma drug shows promise against neurodegenerative diseases, animal studies suggest

cjb250 — Thu, 31 Oct 2024 10:00:09 +0000

Researchers in the UK Dementia Research Institute at the ̽��ֱ�� of Cambridge screened more than 1,400 clinically-approved drug compounds using zebrafish genetically engineered to make them mimic so-called tauopathies. They discovered that drugs known as carbonic anhydrase inhibitors – of which the glaucoma drug methazolamide is one – clear tau build-up and reduce signs of the disease in zebrafish and mice carrying the mutant forms of tau that cause human dementias.

Tauopathies are neurodegenerative diseases characterised by the build-up in the brain of tau protein ‘aggregates’ within nerve cells. These include forms of dementia, Pick's disease and progressive supranuclear palsy, where tau is believed to be the primary disease driver, and Alzheimer’s disease and chronic traumatic encephalopathy (neurodegeneration caused by repeated head trauma, as has been reported in football and rugby players), where tau build-up is one consequence of disease but results in degeneration of brain tissue.

There has been little progress in finding effective drugs to treat these conditions. One option is to repurpose existing drugs. However, drug screening – where compounds are tested against disease models – usually takes place in cell cultures, but these do not capture many of the characteristics of tau build-up in a living organism.

To work around this, the Cambridge team turned to zebrafish models they had previously developed. Zebrafish grow to maturity and are able to breed within two to three months and produce large numbers of offspring. Using genetic manipulation, it is possible to mimic human diseases as many genes responsible for human diseases often have equivalents in the zebrafish.

In a study published today in Nature Chemical Biology, Professor David Rubinsztein, Dr Angeleen Fleming and colleagues modelled tauopathy in zebrafish and screened 1,437 drug compounds. Each of these compounds has been clinically approved for other diseases.

Dr Ana Lopez Ramirez from the Cambridge Institute for Medical Research, Department of Physiology, Development and Neuroscience and the UK Dementia Research Institute at the ̽��ֱ�� of Cambridge, joint first author, said: “Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organisms. They also enable us to do so at scale, something that it not feasible or ethical in larger animals such as mice.”

Using this approach, the team showed that inhibiting an enzyme known as carbonic anhydrase – which is important for regulating acidity levels in cells – helped the cell rid itself of the tau protein build-up. It did this by causing the lysosomes – the ‘cell’s incinerators’ – to move to the surface of the cell, where they fused with the cell membrane and ‘spat out’ the tau.

When the team tested methazolamide on mice that had been genetically engineered to carry the P301S human disease-causing mutation in tau, which leads to the progressive accumulation of tau aggregates in the brain, they found that those treated with the drug performed better at memory tasks and showed improved cognitive performance compared with untreated mice.

Analysis of the mouse brains showed that they indeed had fewer tau aggregates, and consequently a lesser reduction in brain cells, compared with the untreated mice.

Fellow joint author Dr Farah Siddiqi, also from the Cambridge Institute for Medical Research and the UK Dementia Research Institute, said: “We were excited to see in our mouse studies that methazolamide reduces levels of tau in the brain and protects against its further build-up. This confirms what we had shown when screening carbonic anhydrase inhibitors using zebrafish models of tauopathies.”

Professor Rubinsztein from the UK Dementia Research Institute and Cambridge Institute for Medical Research at the ̽��ֱ�� of Cambridge, said: “Methazolamide shows promise as a much-needed drug to help prevent the build-up of dangerous tau proteins in the brain. Although we’ve only looked at its effects in zebrafish and mice, so it is still early days, we at least know about this drug’s safety profile in patients. This will enable us to move to clinical trials much faster than we might normally expect if we were starting from scratch with an unknown drug compound.

“This shows how we can use zebrafish to test whether existing drugs might be repurposed to tackle different diseases, potentially speeding up significantly the drug discovery process.”

̽��ֱ��team hopes to test methazolamide on different disease models, including more common diseases characterised by the build-up of aggregate-prone proteins, such as Huntington’s and Parkinson’s diseases.

̽��ֱ��research was supported by the UK Dementia Research Institute (through UK DRI Ltd, principally funded through the Medical Research Council), Tau Consortium and Wellcome.

Reference
Lopez, A & Siddiqi, FH et al. Carbonic anhydrase inhibition ameliorates tau toxicity via enhanced tau secretion. Nat Chem Bio; 31 Oct 2024; DOI: 10.1038/s41589-024-01762-7

A drug commonly used to treat glaucoma has been shown in zebrafish and mice to protect against the build-up in the brain of the protein tau, which causes various forms of dementia and is implicated in Alzheimer’s disease.

Zebrafish provide a much more effective and realistic way of screening drug compounds than using cell cultures, which function quite differently to living organisms

Ana Lopez Ramirez

Kuznetsov_Peter

Zebrafish

Yes

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Public Domain

‘Far from clear’ new Alzheimer’s drugs will make a difference at a population level, say researchers

cjb250 — Tue, 06 Aug 2024 11:00:50 +0000

Writing in Alzheimer's & Dementia: ̽��ֱ��Journal of the Alzheimer's Association, the team from Cambridge Public Health argue that substantial challenges including the risk-benefit ratio, limited eligibility and high cost of roll-out will limit any benefits of these treatments.

Alzheimer’s disease is often quoted as causing 70% of the 55 million cases of dementia worldwide, though the definition of what constitutes the disease is hotly debated. One characteristic of Alzheimer’s is the build-up of clusters of misfolded proteins, one of these being a form of amyloid, leading to plaques in the brain. ̽��ֱ��cascade hypothesis, a dominant theory in the field, suggests that this triggers a series of processes which together lead to dementia symptoms.

Advances in developing treatments to reduce symptoms and slow down the progression in the early stages of Alzheimer’s has been slow. However, there has been recent excitement surrounding amyloid immunotherapy agents, drugs that harness the immune system to remove amyloid pathology.

Two completed phase III randomised controlled trials of amyloid immunotherapy reported statistically significant reductions in the rate of cognitive and functional decline compared to the placebo.

But as the Cambridge team point out, the effect sizes were small – small enough that a doctor would struggle to tell the difference between the average decline of a patient on the drug and another on placebo, after 18 months. ̽��ֱ��drugs were also associated with significant adverse events, including brain swelling and bleeding; during the phase III trial of one agent, donanemab, there were also three deaths attributed to the treatment.

Crucially, there is little known about the long-term effects of the drugs beyond the 18 month trial periods. Long-term placebo-controlled trials, which would be needed to see if there is any clinically meaningful slowing of decline, are unlikely to be feasible where drugs are already approved.

Despite this, the US Food and Drug Administration has licensed two such drugs. ̽��ֱ��European Medicines Agency (EMA) has recommended rejecting one (lecanemab) predominantly on the grounds that the small effects seen do not outweigh the risk from side effects; it is reviewing the other. ̽��ֱ��UK’s Medicines and Healthcare Products Regulatory Agency (MHRA) is expected to take a decision on both drugs imminently.

Edo Richard, Professor of Neurology at Radboud ̽��ֱ�� Medical Centre in Nijmegen, ̽��ֱ��Netherlands, and co-author, said: “If these drugs are approved by regulators in the UK and Europe, and become available, it is understandable that some people with early Alzheimer’s will still want to try these drugs, given their despair living with this dreadful disease. But there is a lot of hyperbole around the reporting of these drugs, and significant effort will be needed to provide balanced information to patients to enable informed decisions.”

Press coverage of the drugs has implied they are suitable for anyone with a diagnosis of Alzheimer’s. However, while the trials included those with ‘early symptomatic Alzheimer’s disease’, it excluded those with other conditions that may have been contributing to their symptoms. Evidence suggests that the people in the trials represent less than 8% of those in the community with early Alzheimer’s disease. Those in the trials were up to 10 to 15 years younger than those typically presenting to health services with early symptoms.

Lead author Dr Sebastian Walsh, NIHR Doctoral Fellow in Public Health Medicine at Cambridge Public Health, ̽��ֱ�� of Cambridge, added: “If approved, the drugs are likely to be relevant only for a relatively small cohort of Alzheimer’s patients, so potential recipients will need to undergo a range of assessments before being given access to the drugs. Plus, effect sizes seen in the trials are very small and the drugs will need be administered as early in the disease process as possible, when symptoms are mild – and people in these phases of disease can be hard to identify.”

̽��ֱ��resource requirements for rolling out such treatments are likely to be considerable. Even if approved for only a small proportion of Alzheimer’s patients, a much broader group of people will need to be assessed for eligibility, requiring rapid specialist clinical assessment and tests. ̽��ֱ��authors question whether this is the best use of these resources, given the strain health systems are already under. Support would also be required for the large number of Alzheimer’s patients (potentially as many as 92%) found to be ineligible. Those found to have insufficient amyloid to be eligible may then require follow-up assessments to determine eligibility in the future, with the further implications for services this would entail.

Professor Carol Brayne, Co-director of Cambridge Public Health, said: “Even in high-income countries, rolling out such types of treatments at scale is highly challenging, but most dementia occurs in low- and middle-income countries. Health systems in these countries are highly unlikely to have the resources required to offer these new drugs, even to a very narrow group.

“Other compelling evidence suggests that attention to inequalities and health experience across people’s lives could have greater impact on the rates of dementia in populations. Most dementia is more complicated than a single protein.”

̽��ֱ��team concludes that based on current evidence, it is far from clear whether amyloid immunotherapy can ever significantly reduce suffering caused by dementia at scale in the community, and we must continue to explore other approaches.

Professor Brayne added: “With an ageing population, we urgently need effective ways to support people living with dementia, but while the current amyloid immunotherapies may show a glint of promise for very selected groups, it’s clear these drugs will not address dementia risk at scale.”

Reference
Walsh, S et al. Considering challenges for the new Alzheimer’s drugs: clinical, population, and health system perspectives. Alz&Dem; 6 Aug 2024; DOI: 10.1002/alz.14108

Cambridge researchers have cast doubt on whether new amyloid immunotherapy drugs will have the desired effect of significantly reducing the impact of Alzheimer’s disease.

While the current amyloid immunotherapies may show a glint of promise for very selected groups, it’s clear these drugs will not address dementia risk at scale

Carol Brayne

Steven HWG (Unsplash)

Woman sitting in a wheelchair

Yes

Licence type:

Public Domain

Artificial intelligence outperforms clinical tests at predicting progress of Alzheimer’s disease

cjb250 — Fri, 12 Jul 2024 22:30:52 +0000

̽��ֱ��team say this new approach could reduce the need for invasive and costly diagnostic tests while improving treatment outcomes early when interventions such as lifestyle changes or new medicines may have a chance to work best.

Dementia poses a significant global healthcare challenge, affecting over 55 million people worldwide at an estimated annual cost of $820 billion. ̽��ֱ��number of cases is expected to almost treble over the next 50 years.

̽��ֱ��main cause of dementia is Alzheimer’s disease, which accounts for 60-80% of cases. Early detection is crucial as this is when treatments are likely to be most effective, yet early dementia diagnosis and prognosis may not be accurate without the use of invasive or expensive tests such as positron emission tomography (PET) scans or lumbar puncture, which are not available in all memory clinics. As a result, up to a third of patients may be misdiagnosed and others diagnosed too late for treatment to be effective.

A team led by scientists from the Department of Psychology at the ̽��ֱ�� of Cambridge has developed a machine learning model able to predict whether and how fast an individual with mild memory and thinking problems will progress to developing Alzheimer’s disease. In research published today in eClinical Medicine, they show that it is more accurate than current clinical diagnostic tools.

To build their model, the researchers used routinely-collected, non-invasive, and low-cost patient data – cognitive tests and structural MRI scans showing grey matter atrophy – from over 400 individuals who were part of a research cohort in the USA.

They then tested the model using real-world patient data from a further 600 participants from the US cohort and – importantly – longitudinal data from 900 people from memory clinics in the UK and Singapore.

̽��ֱ��algorithm was able to distinguish between people with stable mild cognitive impairment and those who progressed to Alzheimer’s disease within a three-year period. It was able to correctly identify individuals who went on to develop Alzheimer’s in 82% of cases and correctly identify those who didn’t in 81% of cases from cognitive tests and an MRI scan alone.

̽��ֱ��algorithm was around three times more accurate at predicting the progression to Alzheimer’s than the current standard of care; that is, standard clinical markers (such as grey matter atrophy or cognitive scores) or clinical diagnosis. This shows that the model could significantly reduce misdiagnosis.

̽��ֱ��model also allowed the researchers to stratify people with Alzheimer’s disease using data from each person’s first visit at the memory clinic into three groups: those whose symptoms would remain stable (around 50% of participants), those who would progress to Alzheimer’s slowly (around 35%) and those who would progress more rapidly (the remaining 15%). These predictions were validated when looking at follow-up data over 6 years. This is important as it could help identify those people at an early enough stage that they may benefit from new treatments, while also identifying those people who need close monitoring as their condition is likely to deteriorate rapidly.

Importantly, those 50% of people who have symptoms such as memory loss but remain stable, would be better directed to a different clinical pathway as their symptoms may be due to other causes rather than dementia, such as anxiety or depression.

Senior author Professor Zoe Kourtzi from the Department of Psychology at the ̽��ֱ�� of Cambridge said: “We’ve created a tool which, despite using only data from cognitive tests and MRI scans, is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s – and if so, whether this progress will be fast or slow.

“This has the potential to significantly improve patient wellbeing, showing us which people need closest care, while removing the anxiety for those patients we predict will remain stable. At a time of intense pressure on healthcare resources, this will also help remove the need for unnecessary invasive and costly diagnostic tests.”

While the researchers tested the algorithm on data from a research cohort, it was validated using independent data that included almost 900 individuals who attended memory clinics in the UK and Singapore. In the UK, patients were recruited through the Quantiative MRI in NHS Memory Clinics Study (QMIN-MC) led by study co-author Dr Timothy Rittman at Cambridge ̽��ֱ�� Hospitals NHS Trust and Cambridgeshire and Peterborough NHS Foundation Trusts (CPFT).

̽��ֱ��researchers say this shows it should be applicable in a real-world patient, clinical setting.

Dr Ben Underwood, Honorary Consultant Psychiatrist at CPFT and assistant professor at the Department of Psychiatry, ̽��ֱ�� of Cambridge, said: “Memory problems are common as we get older. In clinic I see how uncertainty about whether these might be the first signs of dementia can cause a lot of worry for people and their families, as well as being frustrating for doctors who would much prefer to give definitive answers. ̽��ֱ��fact that we might be able to reduce this uncertainty with information we already have is exciting and is likely to become even more important as new treatments emerge.”

Professor Kourtzi said: “AI models are only as good as the data they are trained on. To make sure ours has the potential to be adopted in a healthcare setting, we trained and tested it on routinely-collected data not just from research cohorts, but from patients in actual memory clinics. This shows it will be generalisable to a real-world setting.”

̽��ֱ��team now hope to extend their model to other forms of dementia, such as vascular dementia and frontotemporal dementia, and using different types of data, such as markers from blood tests.

Professor Kourtzi added: “If we’re going to tackle the growing health challenge presented by dementia, we will need better tools for identifying and intervening at the earliest possible stage. Our vision is to scale up our AI tool to help clinicians assign the right person at the right time to the right diagnostic and treatment pathway. Our tool can help match the right patients to clinical trials, accelerating new drug discovery for disease modifying treatments.”

This work was in collaboration with a cross-disciplinary team including Professor Peter Tino at the ̽��ֱ�� of Birmingham and Professor Christopher Chen at the National ̽��ֱ�� of Singapore. It was funded by Wellcome, the Royal Society, Alzheimer’s Research UK, the Alzheimer’s Drug Discovery Foundation Diagnostics Accelerator, the Alan Turing Institute, and the National Institute for Health and Care Research Cambridge Biomedical Research Centre.

Reference
Lee, LY & Vaghari, D et al. Robust and interpretable AI-guided marker for early dementia prediction in real-world clinical settings. eClinMed; 12 July 2024; DOI: 10.1016/j.eclinm.2024.102725

Cambridge scientists have developed an artificially-intelligent tool capable of predicting in four cases out of five whether people with early signs of dementia will remain stable or develop Alzheimer’s disease.

We’ve created a tool which is much more sensitive than current approaches at predicting whether someone will progress from mild symptoms to Alzheimer’s

Zoe Kourtzi

Yuichiro Chino (Getty Images)

Brain on molecular structure, circuitry, and programming code background

Yes

Over 20,000 people join search for new dementia treatments

cjb250 — Tue, 14 May 2024 09:00:00 +0000

Using the resource, scientists have already been able to show for the first time that two important bodily mechanisms – inflammation and metabolism – play a role in the decline in brain function as we age.

By 2050, approximately 139 million people are expected to be living with dementia worldwide. In the UK, in 2022, UK Prime Minister launched the Dame Barbara Windsor Dementia Mission, part of the government’s commitment to double increase research funding for dementia.

Although there has been recent progress developing drugs that slow down progression of the disease, the two leading treatments only have a small effect, and the vast majority of new approaches that work in animal studies fail when it comes to patient clinical trials.

One explanation for these failures is that the drugs are tested in people who already have memory loss – and by this point, it may be too late to stop or reverse the disease. Hence, there is an urgent need to understand what is going on before people develop symptoms at the very early stages of disease, and to test new treatments before people come to their doctor with cognitive problems. This approach requires a large cohort of participants willing to be recalled for clinical and experimental studies of cognitive decline.

Today, writing in the journal Nature Medicine, scientists led by the ̽��ֱ�� of Cambridge in partnership with the Alzheimer’s Society report how they have recruited 21,000 people aged 17-85 to the Genes and Cognition Cohort within the National Institute for Health and Care Research (NIHR) BioResource.

̽��ֱ��NIHR BioResource was established in 2007 to recruit volunteers keen to engage in experimental medicine and clinical trials across the whole of medicine. Approximately half of its participants are recruited to disease specific cohorts, but the other half are from the general public, and detailed information about their genetics and their physical makeup has been collected. They have all given their consent to be contacted about future research studies.

For the Genes and Cognition Cohort, researchers used a combination of cognitive tests and genetic data, combined with other health data and demographic information, to enable the first at-scale study of cognitive changes. This will allow the team to recruit participants for studies of cognitive decline and new treatments for this.

For example, a pharmaceutical company with a promising new drug candidate to slow the cognitive decline could recruit people through the BioResource based on their profile and invite them to join in the clinical trial. Having a baseline measurement for their cognitive performance will allow scientists to observe whether the drug slows their expected cognitive decline.

Professor Patrick Chinnery from the Department of Clinical Neurosciences at the ̽��ֱ�� of Cambridge and co-Chair of the NIHR BioResource, who has led the project, said: “We’ve created a resource that is unmatched anywhere else in the world, recruiting people who are not showing any signs of dementia rather than people already having symptoms. It will allow us to match individuals to particular studies and speed up the development of much-needed new drugs to treat dementia.

“We know that over time our cognitive function decreases, so we’ve plotted out the expected trajectory of various different cognitive functions over our volunteers’ life course according to their genetic risk. We’ve also asked the question, ‘What are the genetic mechanisms that predispose you to slow or fast cognitive decline as you age?’.”

Using the research, the team have identified two mechanisms that appear to affect cognition as we age and could serve as potential targets to slow down cognitive decline and thereby delay the onset of dementia. ̽��ֱ��first of these is inflammation, with immune cells specific to the brain and central nervous system – known as microglia – causing gradual deterioration of the brain and hence its ability to perform key cognitive functions. ̽��ֱ��second mechanism relates to metabolism – in particular, how carbohydrates are broken down in the brain to release energy.

Professor Chinnery added: “Cognitive decline is a natural process, but when it drops below a particular threshold, that’s when there’s a problem – that is when we would diagnose dementia. Anything that slows that decline will delay when we drop below that threshold. If you could put off the onset of dementia from 65 to 75 or even 85, it would make a huge difference at an individual and at a population level.”

Dr Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said: “This exciting study, funded by Alzheimer’s Society, is an important step in helping us to better understand how the diseases that cause dementia begin, and will aid in the development of new treatments that target the early stages of these diseases.

“ ̽��ֱ��data, from over 20,000 volunteers, helps us to better understand the connection between participants’ genes and cognitive decline and allows for further ground-breaking analysis in future.

“One in three people born in the UK today will go on to develop dementia in their lifetime but research will beat dementia. We need to make it a reality sooner through more funding, partnership working and people taking part in dementia research.”

For further information about how you can join the BioResource and contribute to studies like this one and many others, please visit bioresource.nihr.ac.uk.

̽��ֱ��research was carried out in collaboration with the Medical Research Council Biostatistics Unit and was supported by the Alzheimer’s Society and the NIHR BioResource. ̽��ֱ��researchers were also supported by Wellcome and the Medical Research Council.

Reference
Rahman, MS et al. Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition Cohort participants. Nat Med; 14 May 2024; DOI: 10.1038/s41591-024-02960-5

More than 20,000 volunteers have been recruited to a resource aimed at speeding up the development of much-needed dementia drugs. ̽��ֱ��cohort will enable scientists in universities and industry to involve healthy individuals who may be at increased risk of dementia in clinical trials to test whether new drugs can slow the decline in various brain functions including memory and delay the onset of dementia.

We’ve created a resource that is unmatched anywhere else in the world, recruiting people who are not showing any signs of dementia rather than people already having symptoms

Patrick Chinnery

Halfpoint Images (Getty Images)

Smiling elderly woman speaking to a healthcare worker

Yes