More than 20,000 volunteers have joined efforts to accelerate the development of drugs for dementia

A research team led by the University of Cambridge has recruited more than 20,000 volunteers to a resource aimed at accelerating the development of much-needed dementia drugs. This resource will enable scientists in universities and industry to recruit healthy people into clinical trials to test whether new drugs can slow the decline of various brain functions, including memory, and delay the onset of dementia.

Using this resource, scientists have already shown for the first time that two important mechanisms in the body - inflammation and metabolism - play a role in the decline of brain function with age.

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

While recent progress has been made in developing drugs to slow the progression of the disease, the two leading treatments have only a modest effect, and the vast majority of new approaches that work in animal studies fail in clinical trials in patients.

One explanation for these failures is that the drugs are being tested in people who have already started to lose memory – at which point it may be too late to stop or reverse the disease. There is therefore an urgent need to understand what is happening before people develop symptoms in the earliest stages of the disease, and to test new treatments before people present to their doctors with cognitive problems. This approach requires a large cohort of participants willing to be recruited for clinical and experimental studies of cognitive decline.

In a paper published in Nature Medicine, scientists led by the University of Cambridge in partnership with the Alzheimer's Society report how they recruited 21,000 people aged 17 and over up to 85 years of age to participate in the Genes and Cognition cohort of the National Institute for Health and Health Research (NIHR) BioResource.

NIHR BioResource was established in 2007 to attract volunteers interested in experimental medicine and clinical trials across all areas of medicine. About half of its participants are recruited into disease-specific cohorts, but the other half are recruited from the general population and have detailed information about their genetics and physical condition collected. They all agreed to be contacted regarding future research.

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 conduct the first large-scale study of cognitive change. This will allow the team to recruit participants into research into cognitive decline and new treatments for the condition.

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

Professor Patrick Chinnery, from the Department of Clinical Neuroscience at the University of Cambridge and co-chair of NIHR BioResource, who led the project, said: “We have created a resource like no other in the world by engaging people who do not yet have signs of dementia, rather than those who do. Already have symptoms. This will allow us to match people to specific studies and speed up the development of much-needed new drugs to treat dementia.

“We know that our cognitive function declines over time, so we mapped out the predicted trajectory of various cognitive functions over the lifespan of our volunteers based on their genetic risk. We also asked the question: “What are the genetic mechanisms that predispose to slow or rapid cognitive decline with age?”

Using this research, the team identified two mechanisms that appear to influence cognition with age and may serve as potential targets for slowing cognitive decline and therefore delaying the onset of dementia. The first of these mechanisms is inflammation, in which immune cells specific to the brain and central nervous system—known as microglia—cause a gradual deterioration of the brain and therefore its ability to perform key cognitive functions. The second mechanism has to do with metabolism—specifically, how carbohydrates are broken down in the brain to release energy.

Dr Richard Oakley, Deputy Director of Research and Innovation at the Alzheimer's Society, said: “This exciting research, funded by the Alzheimer's Society, is an important step towards better understanding how the diseases that cause dementia begin and will help develop new treatment methods aimed at the early stages of these diseases.

“Data from more than 20,000 volunteers helps us better understand the link between participants' genes and cognitive decline and allows for further breakthrough analysis in the future.

“One in three people born in the UK today will develop dementia in their lifetime, but research will beat dementia. We need to make this a reality as soon as possible through more funding, partnerships and people getting involved in dementia research."