Having a biological age older than chronological age is associated with a greater likelihood of developing dementia, a new study has shown.
By combining measures of biological ageing and genetic risk, researchers have identified individuals at a higher risk of developing dementia and those who will develop the disease at a younger age.
Funded by the National Institute for Health and Care (NIHR) Maudsley Biomedical Research Centre, the study showed that having a biological age older than chronological age is associated with a greater likelihood of developing dementia, particularly vascular dementia, and with an earlier age of onset across dementia subtypes.
The analysis, led by King's College London researchers, showed that those with both advanced biological ageing and the highest genetic risk, namely those carrying two copies of the APOE ε4 allele, were ten times more likely to develop dementia. These two factors appear to act largely independently, suggesting that there are distinct genetic and biological ageing pathways linked to dementia.
"Our findings suggest that biological ageing data can help identify individuals at risk of dementia before clinical symptoms emerge," says lead author Dr Julian Mutz, King's Prize Research Fellow at the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College London. "By combining genetic factors with potentially modifiable factors captured in biological ageing, we may be able to develop preventative strategies, potentially based on a simple blood test."
Dementia affects an estimated 982,000 individuals in the UK, with projections indicating a rise to 1.4 million by 2040. Although chronological age remains the strongest risk factor, dementia is not an inevitable consequence of ageing and up to 45% of dementia cases could be delayed or prevented through modifying risk factors.
Professor Marian Knight, Scientific Director for NIHR Infrastructure, said: "Dementia affects almost a million people in the UK. Finding ways to detect and treat it earlier will help not only those affected but the families, friends and medical staff who support them. By combining genetics and information on biological ageing, this work from the NIHR Maudsley Biomedical Research Centre team could help us do exactly that - spot dementia sooner and delay it or even stop it in its tracks. For 20 years, the NIHR has focused on empowering experts to tackle the biggest challenges in health and care, ensuring that breakthroughs like these continue to reach the people who need them most."
Metabolomic or biological ageing clocks measure the difference between an individual's actual chronological age and the age that their body appears on the inside. Such clocks can be calculated from measurements of metabolites in the blood, which are small molecules that are produced during the process of metabolism, for example when food is broken down into energy.
Changes in the make-up of different metabolites, the metabolome, have been linked to age-related diseases, and ageing clocks have been associated with risk of earlier death and other adverse health outcomes. In this study researchers have tested whether a metabolomic ageing clock is associated with dementia and its age of onset.
The study, published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association, analysed data from over 220,000 UK Biobank participants. The data included measures of genetic risk for dementia, measures of metabolites in the blood, incidence of dementia and age of onset of dementia.
The data on metabolites were used to calculate a person's metabolomic or biological age, and the difference between this and their chronological age, termed MileAge delta, indicates whether their biological ageing is older or younger than expected for their age.
Nearly 4000 of the participants developed dementia. The analysis found that those people who had a biological age difference from chronological age greater than one standard deviation from the mean (about 16 per cent of people) had a 20 per cent greater risk of developing dementia over time compared to those who had a notably younger biological age. For vascular dementia, it was a 60 per cent greater risk. For those with advanced biological ageing and a high genetic risk of dementia, the likelihood of developing the disease was up to ten times greater than for the average person in the study.
"Our findings suggest that metabolomic ageing clocks capture distinct biological information relevant to dementia risk," said Dr Mutz. "As blood plasma-based clocks are scalable and minimally invasive, they could potentially be part of mid-life screening or used to help refine the selection of individuals to take part in research into prevention or disease-modifying trials for dementia."
The research was supported by the National Institute for Health and Care Research (NIHR) Maudsley Biomedical Research Centre and was a key output of the IoPPN Early Career Award and King's Prize Fellowship awarded to Julian Mutz. Work on polygenic scores used the GenoPred pipeline which was supported by NIHR Maudsley BRC.
Metabolomic ageing (MileAge) in mid-life predicts incident vascular, unspecified and all-cause dementia by Mutz, J. et al was published in Alzheimer's & Dementia: The Journal of the Alzheimer's Association. DOI: 10.1002/alz.71280 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.71280
