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MRC Biostatistics Unit

 
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More than 20,000 volunteers have been recruited to a resource aimed at speeding up the development of much-needed dementia drugs. The cohort will enable scientists in universities and industry to involve healthy individuals who may be at increased risk of dementia in clinical trials to test whether new drugs can slow the decline in various brain functions including memory and delay the onset of dementia.

Using the resource, scientists have already been able to show for the first time that two important bodily mechanisms – inflammation and metabolism – play a role in the decline in brain function as we age. By 2050, approximately 139 million people are expected to be living with dementia worldwide. In the UK, in 2022, UK Prime Minister launched the Dame Barbara Windsor Dementia Mission, part of the government’s commitment to double increase research funding for dementia.

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

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

Writing in the journal Nature Medicine, scientists at the MRC Biostatistics Unit and the Department of Clinical Neurosciences at the University of Cambridge, in partnership with the Alzheimer’s Society, report how they have recruited 21,000 people aged 17-85 to 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 engage in experimental medicine and clinical trials across the whole of medicine. Approximately half of its participants are recruited to disease specific cohorts, but the other half are from the general public, and detailed information about their genetics and their physical makeup has been collected. They have all given their consent to be contacted about future research studies.

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 at-scale study of cognitive changes. This will allow the team to recruit participants for studies of cognitive decline and new treatments for this.

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

Md. Shafiqur Rahman, Research Associate at the MRC Biostatistics Unit and lead author on the paper, said:

"Understanding how our brains work as we age is more important than ever. We studied healthy volunteers from Genes and Cognition study using statistical genetics methodologies, including an in-house developed co-localization method to discover two mechanisms that may affect brain function. Since there is no cure for dementia, these discoveries might lead us to keep our brains healthier for longer and delay the onset of dementia."

Professor Patrick Chinnery from the Department of Clinical Neurosciences at the University of Cambridge and co-Chair of the NIHR BioResource, who has led the project, said:

"We’ve created a resource that is unmatched anywhere else in the world, recruiting people who are not showing any signs of dementia rather than people already having symptoms. It will allow us to match individuals to particular studies and speed up the development of much-needed new drugs to treat dementia."

Using the research, the team have identified two mechanisms that appear to affect cognition as we age and could serve as potential targets to slow down cognitive decline and thereby delay the onset of dementia. The first of these is inflammation, with immune cells specific to the brain and central nervous system – known as microglia – causing gradual deterioration of the brain and hence its ability to perform key cognitive functions. The second mechanism relates to metabolism – in particular, how carbohydrates are broken down in the brain to release energy.

For further information about how you can join the BioResource and contribute to studies like this one and many others, please visit www.bioresource.nihr.ac.uk

Read full paper: Rahman, MS et al. Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition Cohort participants. Nat Med; 14 May 2024; DOI: 10.1038/s41591-024-02960-5