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At risk of dementia? Brain scan shows when you might develop symptoms, study says

The special algorithm could help accelerate the development of drugs to help treat dementia.
PET brain scan
Dr. William Burke goes over a PET brain scan Aug. 14, 2018, at Banner Alzheimer’s Institute in Phoenix. (Matt York | AP)

With just one brain scan and a person’s age, an algorithm can reveal how much time is left ⁠— plus or minus several years ⁠— before someone at risk of developing dementia will begin to experience symptoms of the condition.

The Washington University School of Medicine study found a correlation of 0.9 between the age someone is expected to first show symptoms and the true age of diagnosis (0 equals no correlation and 1 equals perfect correlation). The study was published this month in the journal Neurology.

The technique uses data from “amyloid positron emission tomography (PET),” a widely used brain scan in Alzheimer’s research, to measure the levels of the beta-amyloid protein in the brain. The algorithm offers a new way to analyze this data that helps researchers determine an estimated timeline of symptom onset.

Dementia is an umbrella term for a group of conditions that affect a person’s ability to remember things or make decisions on a daily basis, with Alzheimer’s being the most common type. In 2014, there were an estimated 5 million adults at least 65 years old with dementia in the U.S., according to the Centers for Disease Control and Prevention. By 2060, that number is predicted to rise to nearly 14 million.

While some people may not want to know when they’ll start to forget friends’ names or have difficulty calculating change at the grocery store, others, particularly those with genetic predispositions for dementia, could benefit from having time to prepare for the inevitable changes.

“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?,’” study senior author Dr. Suzanne Schindler, an assistant professor of neurology at the Washington University School of Medicine, said in a statement. “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.”

Key dementia proteins reach a ‘tipping point’

Silently, and over decades, amyloid proteins accumulate in the brain of those who go on to develop dementia before symptoms like forgetfulness and confusion first appear. This build up has a “tipping point” that people reach at different ages, according to Schindler.

Once that point has been reached, amyloid production in the brain shifts into a higher gear. These sticky proteins then build up so much that they disrupt communication between brain cells and eventually kill them, triggering the onset of 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,” Schindler said.

The study found that people who reached the tipping point earlier in life took longer to develop cognitive symptoms compared to those who reached it at older ages. For example, it took participants who hit the tipping point at 50 years old nearly 20 years to develop dementia symptoms, whereas participants who reached 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.”

Researchers studied PET scans from 236 people around the age of 67 who were included in Alzheimer’s research studies through Washington University’s Charles F. and Joanne Knight Alzheimer Disease Research Center. All participants completed at least two brain scans about 4.5 years apart. The team also analyzed more than 1,300 clinical assessments on 180 of the participants done every one to three years.

People with genetic variant reach ‘tipping point’ earlier in life

Age is the No. 1 risk factor for dementia, but people who carry a specific genetic variant called APOE4 are the next most likely to develop the condition.

Carriers of one copy of the variant are two to three times more likely to develop dementia than the general population, according to the study. Carriers of two copies of the variant are 10 times more likely to develop dementia later in life; these people are extremely rare ⁠— comprising only 2% to 3% of those with genetic predispositions.

The study found that people with the variant hit the amyloid tipping point younger than those without it, but once it’s reached, they “followed the same trajectory as everyone else.”

As promising as the algorithm’s results are, the researchers admit PET brain scans are too expensive for routine clinical use. Out-of-pocket costs hover at about $6,000 per scan. But the algorithm could instead contribute to the development of drugs to help treat dementia.

“Most participants in clinical trials designed to prevent or slow Alzheimer’s symptoms do not develop symptoms during the trials. That’s a lot of time and effort — for the participants as well as the researchers — that doesn’t yield useful data,” Schindler said. “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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