By Deirdre Tynan • 20 September 2021 • 10:42
Dementia cases are set to double by 2050 with a growing elderly population.
Researchers can now estimate when a person who is at high risk of Alzheimer’s dementia but has no cognitive symptoms will start showing signs of cognitive decline. The approach is based on data from a single brain scan, combined with the person’s age.
The algorithm, available online in the journal Neurology, uses data from a kind of brain scan known as amyloid positron emission tomography (PET) to gauge brain levels of the key Alzheimer’s protein amyloid beta.
In those who eventually develop Alzheimer’s dementia, amyloid silently builds up in the brain for up to two decades before the first signs of confusion and forgetfulness appear. Amyloid PET scans already are used widely in Alzheimer’s research, and this algorithm represents a new way of analysing such scans to approximate when symptoms will arise. Using a person’s age and data from a single amyloid PET scan, the algorithm yields an estimate of how far a person has progressed toward dementia — and how much time is left before cognitive impairment sets in.
“I perform amyloid PET scans for research studies, and when I tell cognitively normal individuals about positive results, the first question is always, ‘How long do I have until I get dementia?’,” said senior author Suzanne Schindler, an assistant professor of neurology. “Until now, the answer I’d have to give was something like, ‘You have an increased risk of developing dementia in the next five years.’ But what does that mean? Individuals want to know when they are likely to develop symptoms, not just whether they are at higher risk.”
The researchers also accessed over 1,300 clinical assessments on 180 of the participants. The assessments typically were performed every one to three years. Most participants were cognitively normal at the start of data collection, so the repeated assessments allowed the researchers to pinpoint when each participant’s cognitive skills began to slip.
Schindler spent years trying to figure out how to use the data in amyloid PET scans to estimate the age at which symptoms would appear. The breakthrough came when she realized that amyloid accumulation has a tipping point and that each individual hits that tipping point at a different age. After this tipping point, amyloid accumulation follows a reliable trajectory.
“You may hit the tipping point when you’re 50; it may happen when you’re 80; it may never happen,” Schindler said. “But once you pass the tipping point, you’re going to accumulate high levels of amyloid that are likely to cause dementia. If we know how much amyloid someone has right now, we can calculate how long ago they hit the tipping point and estimate how much longer it will be until they are likely to develop symptoms.”
People in the study who reached the tipping point at younger ages took longer to develop cognitive symptoms than those who reached it later in life. Participants who hit the tipping point at age 50 typically took nearly 20 years to develop symptoms; those who hit it at age 80 took less than 10 years.
“When we look at the brains of relatively young people who have died with Alzheimer’s, they typically look pretty healthy, other than Alzheimer’s,” Schindler said. “But older people more frequently have damage to the brain from other causes, so their cognitive reserves are lower, and it takes less amyloid to cause impairment.”
The power of this new technique is that it requires just one brain scan, plus the person’s age. With that data, the model can estimate the time to symptom onset, plus or minus several years.
At an out-of-pocket cost of about $6,000, amyloid PET brain scans are too expensive for routine clinical use. However, this algorithm could help accelerate the pace of drug development by streamlining clinical trials.
“Most participants in clinical trials designed to prevent or slow Alzheimer’s symptoms do not develop symptoms during the trials,” Schindler said. “That’s a lot of time and effort — for the participants as well as the researchers — that doesn’t yield useful data. If we could do trials only on people who are likely to develop symptoms in the next few years, that would make the process of finding therapies much more efficient.”
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Deirdre Tynan is an award-winning journalist who enjoys bringing the best in news reporting to Spain’s largest English-language newspaper, Euro Weekly News. She has previously worked at The Mirror, Ireland on Sunday and for news agencies, media outlets and international organisations in America, Europe and Asia. A huge fan of British politics and newspapers, Deirdre is equally fascinated by the political scene in Madrid and Sevilla. She moved to Spain in 2018 and is based in Jaen.
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