Research

Here we set out some of latest thinking on the diseases of the brain and nervous system that lead to dementia.

Much of this thought and the practical research it inspires may lead nowhere: theories are literally tested to destruction. Not all research is equally rigorous and the many well-designed trials can fail.

Sometimes there are breakthroughs that promise real advances in treatment and management of disease but these can take many years to become widely available and, over time, found to be more or less effective than expected. So please treat all that you read here with caution, but not without hope…

Hearing with our brains

A hearing test to measure how the brain responds to sound, rather than how well the ears work, could help diagnose dementia according to researchers.

In the nonverbal ‘brain hearing’ test, people are asked to identify one sound played into one ear while a different sound is played into the other. The test shows how effectively the brain separates and interprets competing noises, such as when in a busy environment like a restaurant.

In a study of nearly 90 people, including those with Alzheimer’s disease, frontotemporal dementia and language-led dementia (primary progressive aphasia) as well as a group of healthy volunteers, those with most forms of dementia performed worse in the nonverbal test.

The brain had to separate competing sounds and the person pointed to pictures matching the sounds. The results across all participants closely related to their real life hearing experience and, for people with dementia, the brain-related changes seen in their conditions.

The study was carried out by the Dementia Research Centre at UCL Queens Square Institute of Neurology and funded by The Alzheimer’s Society.

The results suggest that the nonverbal test could distinguish those with dementia, particularly Alzheimer’s disease, from those without.

Joint lead author of the study, Dr Chris Hardy, said: ‘We hear with our ears, but we also hear with our brains, and dementia can affect how the brain interprets sound, even when the ears themselves are working normally.

‘When we’re in a busy environment, such as a pub or restaurant with lots of people talking, the brain must work hard to focus on a single voice. That’s an example of the type of ability we refer to as ‘brain hearing’. This is challenging for everybody, but this study shows that it’s even harder for people with a form of dementia, like Alzheimer’s disease.’

Although loss of hearing can be a risk factor in dementia and an early symptom in people aged between 40 and 65, hearing loss alone is not evidence of dementia, say researchers. This study shows which brain mechanisms are affected, but not that general hearing loss is a warning sign of dementia.

“Understanding whether hearing loss is associated with the ear or the brain is critically important,” adds Dr. Hardy. “If you have brain hearing loss, but not peripheral hearing loss, then hearing aids are unlikely to help.”

The study also points up the importance of hearing for people with dementia.

Jason Warren, Professor of Neurology and Consultant at the UCL Queen Square Institute of Neurology and senior author of the paper, said:

“Many people with dementia find themselves sensitive to sound and begin avoiding noisy places, which can limit social activity. As this study highlights, we ought to explore how to make listening spaces and communication more accessible, so people don’t become isolated”.

More information on this research can be found on The Alzheimer’s Society website.

Lacanemab: the big news

When this new Alzheimer’s medication was licensed for use in the UK this summer, what really attracted the headlines was the sheer cost of it.

Best cost estimates were around £20,000 a year for the drug and a further £20,000 a year in monitoring and administration of it. In fact it is so expensive that NICE (National Institute for Health and Care Excellence) decided it was too expensive for use by the NHS.

The possibility of serious side effects is the reason for the high cost of administering it – by infusion -and monitoring patients closely for possible adverse reactions. On top of this, trials suggest the drug, trade name Leqembi, is effective only for up to a year and only for those in the earliest stages of Alzheimer’s.

But all this tends to obscure the real news: that for the first time we have a drug that actually treats the disease, not just the symptoms of it. It is the first real breakthrough in decades.

Lacanemab is a monoclonal antibody, a laboratory produced protein that binds to and attacks the amyloid plaques in the brains of Alzheimer’s patients which is thought to cause their dementia. This monoclonal antibody (MAB) recognises the amyloid (another form of protein) and works with the brain’s immune cells to clear the build-up of this material which is thought to be toxic to brain cells.

MABs are already used in the diagnosis and treatment of other diseases, including some cancers, often to carry drugs or toxins directly to cancer cells. Anti-amyloid MABs are the first AD therapies that can actually slow down the disease by interfering with the basic biological processes of it.

The fact that this therapy works at all supports the view that it is the build up of amyloid that is a root cause of AD and it therefore clears the way for further development of amyloid targeting therapies and new therapies for other neurodegenerative diseases.

Donanemab “poor value”

The latest new treatment for early stage Alzheimer’s Disease, donanemab, has been licensed for use in the UK, but rejected as too costly for NHS use. Donanemab, is similar in its action to lacanemab, which has already suffered the same fate. The National Institute for Health and Care Excellence (NICE) has judged it poor value for money at a similar price to lacanemab and effective for less than a year.

The Alzheimer’s Society’s Chief Policy and Research Officer, Professor Fiona Carragher said: “In other diseases, like cancer, treatments have become more effective, safer and cheaper over time and we hope to see similar progress in dementia.”

In June, both new drugs, donanemab and lacanemab, have been rejected for a second time by NICE. The Institute’s appraisal committee again concluded the drugs remained poor value for money. Helen Knight, director of medicines evaluation, said: “ We have done everything we possibly can to achieve a positive outcome…However the committee concluded the small benefits of donanemab and lacanemab shown in the clinical trials and the lack of long term evidence of effectiveness, together with the substantial resources the NHS would need to commit to the treatments, means if they were approved they could displace other essential treatments and services that deliver significant benefits to patients.”

Professor Fiona Garragher, chief policy and research officer at The Alzheimer’s Society said: “Even if the drugs were available on the NHS now, they would be hard to access because the health system is not ready to deliver them.” She added that she hoped the drugs would become more effective, safer and cheaper over time.

Dementia is ‘highly preventable’

The Lancet Commission on dementia, which in 2020 identified 12 risk factors for the development of dementia has now identified two more.

Factors identified in 2020 were:

Low educational achievement
Hearing loss
Hypertension
Smoking
Obesity
Depression
Physical inactivity
Diabetes
Excessive alcohol consumption
Traumatic brain injury
Air pollution
Social isolation

To these we can now add:

Untreated loss of vision
High LDL cholesterol

There is now compelling evidence for all these factors according to The Lancet Commission’s 2024 update based on further meta analysis of research studies.And it is really good news, says the commission, in that all these factors can be either minimised or eliminated, offering new hope of prevention and care.

In their update, the Lancet Commission says: “As people live longer, the number of people who live with dementia continues to rise, even as the age-specific incidence decreases in high-income countries, emphasising the need to identify and implement prevention approaches.

“We have summarised the new research since the 2020 report of the Lancet Commission on dementia, prioritising systematic reviews and meta-analyses and triangulating findings from different studies showing how cognitive and physical reserves develop across the life course and how reducing vascular damage (eg, by reducing smoking and treating high blood pressure) is likely to have contributed to a reduction in age-related dementia incidence.

“Evidence is increasing and is now stronger than before that tackling the many risk factors for dementia that we modelled previously… reduces the risk of developing dementia. In this report, we add the new compelling evidence that untreated vision loss and high LDL cholesterol are risk factors for dementia”.

Quick and easy dementia tests?

A blood test for early stage Alzheimer’s Disease and similar brain diseases could be available to the NHS within five years.

UK-wide trials are being conducted by teams of researchers to develop blood tests that will boost early diagnosis of all the diseases that lead to dementia. One team, from University College London, and another from Dementias Platform UK, University of Oxford, will be carrying out the clinical trials.

Reliably accurate blood tests will complement the development of a new generation of drugs, like lacanemab and donanemab, that are most effective at treating early stage disease. At present it can take years for a formal diagnosis to be made and, even then, it may not be fully accurate.

NHS England reports that only 2% of people who receive a dementia diagnosis have actually undergone tests such as PET scans and lumbar punctures that produce the most reliable diagnosis at an early stage.

According to NHS England 478,822 people had a recorded dementia diagnosis in February 2024, an increase of 1,199 since the previous month.

The research teams will start recruiting trials participants soon. Although blood tests have been developed for AD and other dementia-causing diseases that show very promising results, none has yet been tested in ‘real life’ situations.

The two research teams will take different approaches. The Oxford based READOUT study will test both existing and new blood tests for a range of types of dementia and test whether or not the test can identify the diseases at different stages. The second study, ADAPT, based at University College London, will focus on the most promising test for Alzheimer’s disease, which measures levels of a protein called p-tau217. This increases in the blood as other proteins build up in the brain during the development of Alzheimer’s disease. The researchers will carry out a clinical trial to see whether measuring p-tau217 in the blood increases the rate of diagnosis for AD.

The two-pronged approach to the research is designed to boost the chance of providing enough evidence to validate the use of blood tests in the NHS.

If you’re interested in taking part in this research, please visit Dementias Platform UK’s website, or get in touch with our Information Services team on infoline@alzheimersresearchuk.org or 0300 111 5 111.