More than 20,000 people are taking part in the UK’s search for new treatments for dementia

More than 20,000 volunteers have been recruited for a resource aimed at accelerating the development of much-needed dementia drugs. The cohort will enable scientists at universities and industry to engage healthy individuals with a possible increased risk of dementia in clinical trials to test whether new drugs can delay the decline of various brain functions, including memory, and prevent the onset of dementia. to delay.

Using the resource, scientists have been able to demonstrate for the first time that two key body mechanisms – inflammation and metabolism – play a role in the decline of brain function as we age.

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

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

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

Writing in the diary Naturopathyscientists led by the University of Cambridge in collaboration with the Alzheimer’s Society report how they have recruited 21,000 people aged 17 to 85 into the Genes and Cognition Cohort within the National Institute for Health and Care Research (NIHR) BioResource.

The NIHR BioResource was established in 2007 to recruit volunteers keen to participate in experimental medicine and clinical trials across medicine. About half of the participants are recruited from disease-specific cohorts, but the other half come from the general public, and detailed information is collected about their genetics and physical composition. They have all given permission to be contacted about 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 enable the first large-scale study of cognitive changes. This allows the team to recruit participants for research into cognitive decline and new treatments for it.

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

Professor Patrick Chinnery from the University of Cambridge’s Department of Clinical Neurosciences and co-chair of the NIHR BioResource, who led the project, said: “We have created a resource unrivaled anywhere else in the world, by recruiting people who show no signs of exhibit dementia, rather than people already having symptoms. It will allow us to connect individuals to specific trials and accelerate the development of much-needed new drugs to treat dementia.

“We know that our cognitive function declines over time, so we mapped the expected trajectory of different cognitive functions over the life course of our volunteers based on their genetic risk. We also asked the question: ‘What are the genetic risks?’ mechanisms that predispose you to slow or rapid cognitive decline as you age?

Using the research, the team identified two mechanisms that appear to influence cognition as we age and could serve as potential targets to slow cognitive decline and thereby delay the onset of dementia. The first of these is inflammation, where immune cells specific to the brain and central nervous system – known as microglia – cause a gradual deterioration of the brain and thus the brain’s ability to perform important cognitive functions. The second mechanism involves metabolism – specifically the way carbohydrates are broken down in the brain to release energy.

Professor Chinnery added: ‘Cognitive decline is a natural process, but if it falls below a certain threshold then there is a problem – that is when we would diagnose dementia. Anything that slows that decline will slow if we fall below that threshold. you could delay the onset of dementia from age 65 to 75 or even 85, it would make a huge difference on an individual and population level.”

Dr. Richard Oakley, Associate Director of Research and Innovation at Alzheimer’s Society, said: “This exciting study… is an important step in helping us better understand how the diseases that cause dementia, and will help in the development of new diseases. ” treatments that target the early stages of these diseases. The data, from more than 20,000 volunteers, will help us better understand the link between participants’ genes and cognitive decline and enable further groundbreaking analyzes in the future.

“One in three people born in Britain today will develop dementia in their lifetime, but research will beat dementia. We need to make this a reality sooner through more funding, collaboration and people taking part in dementia research.”