Longevity Briefs: Combining Measures Of Biological Ageing Could Predict Cognitive Decline In Midlife

Posted on 26 April 2022

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

Why is this research important: We know that different people experience cognitive ageing and decline at different rates. Identifying rapid cognitive decline early on means that measures can be swiftly taken to delay or prevent further deterioration and the development of dementia. Unfortunately, underlying changes in the brain that lead to dementia occur many years before significant cognitive decline actually occurs. Methods for measuring how rapidly someone is undergoing cognitive ageing could help to solve this problem.

One approach is to measure patterns of DNA methylation, a process in which molecular ‘tags’ are added or removed from DNA in order to control which regions of the DNA molecule are available to be read. These tags change predictably throughout life and can estimate someone’s ‘true’ biological age, as opposed to their chronological age – the number of years since they were born. A more in-depth explanation of DNA methylation and its relationship with ageing can be found here. Another approach is to look at the brain’s structure, as this is also known to change in older age.

Methyl groups ‘tag’ the DNA molecule and affect how it is packaged. This influences which sections of the DNA can be accessed and used to make proteins.

What did the researchers do: In this study, researchers collected DNA methylation data (measured from blood samples), brain images, and cognitive function test scores from over 1000 participants in the CARDIA study over a period of 15 years. Biological age was measured using four different methods (known as clocks) for equating DNA methylation to ageing, and these measurements were made once when participants had an average age of 40, then again 5 years later. Five years after that, some participants underwent magnetic resonance imaging (MRI) brain scans. These scans were used to estimate brain age using a technique that combines machine learning with existing data about how the structure of the brain changes with age. Participants also took tests of cognitive function. Both the MRI scans and the cognitive function tests were repeated 5 years later.

Mid-life epigenetic age, neuroimaging brain age, and cognitive function: coronary artery risk development in young adults (CARDIA) study https://doi.org/10.18632/aging.203918

Key takeaway(s) from this research: The researchers found that faster biological ageing as indicated by brain structure changes and one of the DNA methylation clocks (called GrimAge) showed a significant correlation with poorer cognitive function. The other three DNA methylation clocks didn’t show a significant correlation with reduced cognitive performance. Interestingly, while both GrimAge and structural changes were associated with cognitive decline, they did not correlate, suggesting that they might be measuring two independent facets of brain ageing.

The researchers were then able to combine these two measurements into a single model with an even better ability to predict cognitive function. Such a model could prove helpful in detecting those most likely to suffer age-related cognitive decline, especially considering that it is able to predict cognitive function in midlife, during which interventions are likely to have the most significant impact.


Mid-life epigenetic age, neuroimaging brain age, and cognitive function: coronary artery risk development in young adults (CARDIA) study: https://doi.org/10.18632/aging.203918

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