An algorithm has been devised to estimate when a person who is likely to develop Alzheimer’s disease, but has no cognitive symptoms, will start showing signs of the condition.
The new approach uses data from an amyloid positron emission tomography (PET) brain scan to gauge brain levels of the key Alzheimer’s protein amyloid beta.
In those who will 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, one the ‘tipping point’ is reached in amyloid accumulation.
Amyloid PET scans already are used widely in Alzheimer’s research, and this algorithm – devised by researchers at Washington University School of Medicine in St. Louis – 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.”
Schindler and colleagues analysed amyloid PET scans from 236 people participating in Alzheimer’s research studies through Washington University’s Charles F. and Joanne Knight Alzheimer Disease Research Center.
The participants were an average of 67 years old at the beginning of the study. All participants underwent at least two brain scans an average of four-and-a-half years apart.
The researchers applied a widely used metric known as the standard uptake value ratio (SUVR) to the scans to estimate the amount of amyloid in each participant’s brain at each time point.
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 with the realisation 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 ten 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.”
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