Significant breakthroughs in dementia research
As Join Dementia Research celebrates 9 years of matching volunteers to dementia studies, it is timely to reflect on the progress dementia research has made both with our help and more broadly in recent years.
It is encouraging to know that at any one time, there are around 150 dementia research studies underway in the UK – many supported by the NIHR and Join Dementia Research. The UK is second only to the United States in terms of the volume of dementia research we conduct.
But what really makes the UK stand out is the huge variety of dementia research that is carried out here. Many UK studies are looking at the causes of different types of dementia and how these are diagnosed. Researchers are trying to find ways to diagnose dementia earlier as well as improve the way we treat the different forms of the disease. And treatment doesn’t only mean drugs. It covers all the strategies and approaches around dementia to improve the lives of people living with dementia – and even prevent people getting it in the first place.
Research is unravelling the factors that increase people’s risk of the disease. It seeks to find better care for people as their dementia progresses. And it strives to find ways in which end of life care is the best it can be.
There have been some major advances in dementia research in the UK and worldwide in recent years and we’ve highlighted some significant projects below.
New genes linked to Alzheimer’s disease
In 2022, a major international study linked 42 genes to Alzheimer’s disease for the first time.
Scientists from eight countries, including from Cardiff University, identified 75 genes that were associated with an increased risk of developing the disease. Of these, 42 had not been connected to Alzheimer’s disease before.
The researchers compared a group of 111,326 people with Alzheimer’s disease with 677,663 healthy individuals to look for differences in their genetic make-up.
The findings confirmed the role of the proteins amyloid-beta and tau that build up in and around nerve cells in the brain as the disease progresses.
It also found that inflammation and ‘over-aggressive’ activity in the brain’s immune cells play a role in the disease.
These genes offer new targets for researchers to look at when developing potential treatments for Alzheimers.
The scientists used the findings to devise a genetic risk score that could predict which patients with cognitive impairment would go on to develop Alzheimer’s disease. This could help when recruiting people for clinical trials of drugs aimed at treating the disease in the earliest stages.
Later that year, the team also found two further genes and specific mutations in those genes which they were able to link to Alzheimer’s.
Risk factors for Alzheimer’s which we can control
Earlier research found that 40% of dementia diagnoses could be prevented or delayed by targeting 12 risk factors over which we have some control.
The Lancet Commission on dementia, prevention, intervention and care in 2017 identified nine modifiable factors that increased the risk of dementia. In 2020, this list was updated to 12.
The 12 risk factors are: Excessive alcohol consumption, traumatic brain injury, air pollution, hypertension, obesity, smoking, physical inactivity, diabetes, depression, lack of education in early life, hearing loss, low social contact
The factors associated with the greatest proportion of dementia cases in the population are less education in early life, hearing loss in mid-life, and smoking in later life (7%, 8%, and 5%, respectively).
The Commission assessed that 3% of dementia cases could be attributed to head injuries in mid-life. One percent of cases were linked to excessive alcohol consumption (of more than 21 units per week) in mid-life. Two percent could be linked to exposure to air pollution in later life.
Better use of existing medicines
There are four treatments for different forms of dementia which are licensed for use in the UK: donepezil, rivastigmine, galantamine, memantine.
The drugs are effective for two of the common causes of dementia, Alzheimer’s disease and Lewy body dementia, but not for vascular dementia and frontotemporal dementia.
Thanks to the 2014 DOMINO study, supported by the NIHR, we know that donepezil or a combination of donepezil and memantine can continue to slow the progress of Alzheimer’s dementia even in the later stages.
The study compared donepezil to memantine as the two drugs work in different ways. They also looked at whether a combination of the two drugs could be more effective.
In the past, patients were taken off these drugs once their disease had gone beyond the earlier stages. Now, thanks to the research, doctors in the UK and around the world have changed how they treat patients with dementia.
New medicines for dementia
A new class of drugs is emerging that slow the progression of Alzheimer’s disease by targeting one of the root biological causes of the disease – amyloid beta protein.
All three of the newest drugs have been trialled in the UK, with volunteers from Join Dementia Research taking part.
Aducanemab was the first drug of this type, approved for use in the USA in 202, but wasn’t approved in Europe due to lack of clinical benefit. While aducanemab can slow the build-up of amyloid beta protein, it does not significantly improve memory or thinking. It has recently been reported that aducanemab is now being phased out, but it has paved the way for two new amyloid-reducing drugs.
In 2022, a trial of lecanemab showed the drug was able to slow memory loss and decline in thinking skills by around 27%. It gained approval in the USA in 2022 and is under review in Europe and the UK. Some experts think the risks of lecanemab outweigh the benefits, as it did cause brain swelling in some patients.
Donanemab is the latest drug to be trialled, with results made public in 2023. The drug slowed memory and thinking decline by approximately 35% in people with early stage Alzheimer’s. Three quarters of those on the trial had amyloid beta removed from their brains by the end of the study as assessed by brain scanning.
Donanemab, like lecanemab, has been submitted for approval in the UK. If either drug is approved, it will then be assessed by the National Institute of Health and Care Excellence who will decide if it can be made available on the NHS.
These are exciting times for dementia research, with new treatments on the horizon. But just as important as the trials of these drugs, are the studies that look at improving quality of life and overall care for people with all forms of dementia.
This is just a small snapshot of some of the dementia research that has happened and is happening right now. These studies demonstrate how much difference research can make and how important it is to keep moving our knowledge and understanding forward.
Thank you to all our volunteers and researchers for helping to make breakthroughs like these possible.