More than 20,000 volunteers join effort to accelerate dementia drug development

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. The resource will allow scientists at universities and industry to recruit healthy people to 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 deterioration of brain function with age.

By 2050, an estimated 139 million people worldwide are expected to be living with dementia. 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.

Although progress has been made in recent years in developing drugs that slow the progression of the disease, the two leading treatments have only modest effects, 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 drugs are being tested on 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 the journal 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 to 85 to take part in the Genes and Cognition cohort within the National Institute for Health and Research (NIHR) BioResource.

The NIHR BioResource was set up in 2007 to recruit volunteers interested in experimental medicine and clinical trials across all areas of medicine. Around half of its participants are recruited into disease-specific cohorts, but the other half are drawn from the general population, and detailed information about their genetics and fitness is collected. All have agreed to be contacted about future research.

For the Genes and Cognition cohort, the researchers used a combination of cognitive tests and genetic data, along with other health and demographic information, to conduct the first large-scale study of cognitive change. This will allow the team to recruit participants for research into cognitive decline and new treatments for the condition.

For example, a pharmaceutical company with a promising new drug to slow cognitive decline could recruit people through BioResource based on their profile and invite them to participate in a clinical trial. Having a baseline measurement of their cognitive performance would 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 the NIHR BioResource, which led the project, said: "We have created a resource that is unique in the world, recruiting people who do not yet show signs of dementia, rather than those who already have symptoms. This will allow us to match people to specific studies and accelerate the development of much-needed new drugs to treat dementia.

"We know that our cognitive function declines over time, so we projected the predicted trajectory of different cognitive functions over the life of our volunteers based on their genetic risk. We also asked, 'What are the genetic mechanisms that predispose us to slow or rapid cognitive decline with age?'

Using this research, the team identified two mechanisms that appear to impact 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 brain- and central nervous system-specific immune cells – known as microglia – cause a gradual deterioration in the brain and therefore its ability to perform key cognitive functions. The second mechanism involves 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 treatments that target the early stages of these diseases.

“Data from more than 20,000 volunteers helps us better understand the relationship 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 conquer dementia. We must make this a reality as soon as possible through more funding, partnerships and people getting involved in dementia research."