Some people enter old age physically fit and mentally alert. Others feel frail or forgetful much earlier than expected. “The way we age has little to do with how many times we’ve been around the sun,” says Ahmad Hariri, Professor of Psychology and Neuroscience at Duke University.
Now scientists at Duke University, Harvard University and the University of Otago in New Zealand have developed a freely available tool that can be used to determine how quickly someone is ageing while still relatively healthy, based on a snapshot of the brain. Based on a single MRI scan of the brain, the tool can estimate the risk of chronic diseases that typically appear decades later. This information could help motivate people to adopt a healthier lifestyle and diet. The results were published in the journal Nature Aging.
Finding the Right Measure for the Speed of the Ageing Process
In older people, the tool can predict years before symptoms appear whether someone will develop dementia or other age-related diseases, when the chances of slowing the progression of the disease are even better.
Finding ways to slow age-related decline is the key to a healthier and longer life. But first, “we need to figure out how to accurately monitor ageing,” says Hariri. Several algorithms have been developed to measure how well a person is ageing. However, most of these “age clocks” are based on data collected from people of different ages at one point in time, rather than observing the same people as they age, Hariri said. “What looks like faster aging may simply be due to different exposures,” such as leaded gasoline or cigarette smoke, which are typical of a particular generation, Hariri explained.
The challenge is to find a measure of the speed of the process that is not distorted by environmental or historical factors that have nothing to do with ageing. To do this, the researchers drew on data from 1,037 people who had been studied since birth as part of the Dunedin Study, named after the New Zealand city where they were born between 1972 and 1973. Every few years, the Dunedin Study researchers looked at changes in the participants’ blood pressure, body mass index, glucose and cholesterol levels, lung and kidney function and other values – even gum recession and tooth decay. They used the overall pattern of changes in these health markers over a period of nearly 20 years to establish a value for each person’s rate of ageing.
Faster Ageing and Higher Dementia Risk
The new tool, called DunedinPACNI, was trained to estimate this ageing score using only information from a single MRI scan of the brain performed on 860 participants in the Dunedin study at the age of 45. The researchers then used it to analyze brain scans from other data sets of people from the UK, the US, Canada and Latin America.
Across all data sets, they found that people who aged faster according to this measure performed worse on cognitive tests and showed faster shrinkage of the hippocampus, a region of the brain that is important for memory. Even more sobering was that they were also more likely to suffer cognitive decline in later life. In an analysis, the researchers examined brain scans of 624 people aged 52 to 89 from a North American study on Alzheimer’s risk. Those who were classified as aging the fastest at the start of the study had a 60% higher risk of developing dementia in the following years. They also showed memory and thinking problems earlier than those who aged more slowly.
Correlations Between Ageing Speed and Chronic Health Problems
The researchers also found that people whose DunedinPACNI scores indicated faster aging were more likely to suffer from an overall decline in their health, not just a decline in their brain function. People with higher aging scores were frailer and more likely to suffer from age-related health problems such as heart attacks, lung disease or strokes. The most rapidly ageing people were 18% more likely to develop a chronic disease within the next few years compared to people with an average ageing rate.
Even more alarming, according to the researchers, they were also 40% more likely to die within this period than people who aged more slowly. The correlations between rate of aging and dementia were just as strong in other demographic and socioeconomic groups as in those on which the model was trained, including a sample of people from Latin America as well as participants from the UK with low income or non-white skin color.
Identifying People Who May Develop Alzheimer’s Disease Earlier
The work is important because people around the world are living longer. In the coming decades, the number of people over 65 is expected to double, accounting for almost a quarter of the world’s population by 2050. The economic burden of dementia is already enormous. For example, research suggests that the global cost of Alzheimer’s care will rise from US$1.33 trillion in 2020 to US$9.12 trillion in 2050 – comparable or even higher than the cost of diseases such as lung disease or diabetes, which affect more people. Effective treatments for Alzheimer’s have so far been difficult to find. Most approved drugs can alleviate the symptoms, but cannot stop or reverse the disease.
One possible explanation for why drugs have not worked so far is that they have been used too late, when the Alzheimer’s proteins that accumulate in and around the nerve cells have already caused too much damage. In future, however, the new tool could make it possible to identify people who may develop Alzheimer’s disease earlier and evaluate measures to treat them – before the brain damage becomes too extensive and without having to wait decades for follow-up examinations.
New Tool Important for Prognosis and Prediction of Disease Risk
In addition to predicting our risk of dementia over time, the new clock will also help scientists better understand why people with certain risk factors, such as sleep disorders or mental illness, age differently, said lead author Ethan Whitman, who is working toward a doctorate in clinical psychology with Hariri and the study’s co-authors, Terrie Moffitt and Avshalom Caspi, also professors of psychology and neuroscience at Duke University.
More research is needed to develop DunedinPACNI from a research tool into something that has practical applications in healthcare, they say. In the meantime, however, the team hopes the tool will help researchers with access to brain MRI data to measure the rate of aging in a way that is not possible with aging clocks based on other biomarkers, such as blood tests. “We hope it will become an important new tool for prognosis and prediction of disease risk, particularly Alzheimer’s and related dementias, and perhaps also provide better insight into disease progression,” says Hariri.