Time Until Alzheimer’s Dementia Symptoms Appear Can Be Estimated via Brain Scan

Predict Alzheimer’s disease dementia by brain amyloid level and age.

Researchers at Washington University School of Medicine in St. Louis have developed a method to estimate when a person who may have Alzheimer’s disease but has no cognitive symptoms will begin to show signs of Alzheimer’s disease.

The algorithm, available online in the Journal of Neurology, uses brain scan data called amyloid positron emission tomography (PET) to measure brain levels of the key Alzheimer’s amyloid beta protein.

In those who eventually develop Alzheimer’s disease, amyloid accumulates silently in the brain for up to two decades before the first signs of confusion and forgetfulness appear. Amyloid PET scans have been widely used in Alzheimer’s disease research, and the algorithm represents a new way to analyze such scans to estimate when symptoms appear. The algorithm uses a person’s age and data from a single amyloid positron emission tomography scan to return an estimate of the degree to which a person has progressed to dementia and the time remaining before cognitive decline.

“I do amyloid positron emission tomography for research. When I tell people with normal cognition about the positive results, the first question is always,’How long do I have dementia?'” Author, MD Susanna Sind Le said, Doctor. , Assistant Professor of Neurology. “Until now, the answer I have to give is,’You have a higher risk of dementia in the next five years.’ But what does this mean? People want to know when they might have symptoms, not just them. Is the risk of the increase.”

Schindler and his colleagues used the Charles F. and Joanne Knight Alzheimer’s Disease Research Center at the University of Washington to analyze the amyloid positron emission tomography scans of 236 people involved in Alzheimer’s disease research. At the beginning of the study, the average age of the participants was 67 years. All participants underwent at least two brain scans, an average of 4.5 years apart. The researchers applied a widely used metric in the scan, called the standard absorption value ratio (SUVR), to estimate the amount of amyloid in each participant’s brain at each point in time.

The researchers also interviewed more than 1,300 clinical evaluations of 180 participants. The assessment is usually carried out every one to three years. Most participants had normal cognition at the beginning of the data collection, so repeated evaluations allowed researchers to determine when each participant’s cognitive abilities began to decline.

Schindler spent years trying to figure out how to use data from amyloid positron emission tomography to estimate the age of symptoms. He made a breakthrough when he realized that there was a critical point in the accumulation of amyloid and that everyone reached the critical point at different ages. After this critical point, the accumulation of amyloid follows a reliable path.

“You can reach the tipping point when you are 50; it may happen when you are 80; it may never happen,” Schindler said. “But once you pass the tipping point, you will accumulate high levels of amyloid, which can lead to dementia. If we know how much amyloid a person has now, we can calculate how long they were before Reach the tipping point and estimate how long it will take before they show symptoms.”

Compared with people who reached the tipping point in later life, those who reached the tipping point earlier in the study had cognitive symptoms longer. Participants who reached the tipping point in their 50s usually took nearly 20 years to develop symptoms; those who beat him in their 80s took less than 10 years.

“When we look at the brains of relatively young people who have died of Alzheimer’s, they usually look healthy except for Alzheimer’s,” Schindler said. “But older people more often suffer brain damage due to other reasons, so they have lower cognitive reserves and require less amyloid to cause damage.”

The power of this new technology is that it only requires a brain scan, plus the person’s age. With these data, the model can estimate the time to symptoms, plus or minus several years. In this study, in the range of 0 (no correlation) to 1 (complete correlation), the correlation between the expected age of onset of symptoms and the actual age of diagnosis was better than 0.9.

As we age, mutations in the APOE4 gene are the strongest risk factor for Alzheimer’s dementia. People with one variant copy are two to three times more likely to develop Alzheimer’s disease than the general population, and people with two copies are 10 times more likely to develop Alzheimer’s disease than the general population. In this study, people with high-risk variants reached the tipping point younger, but after that, they followed the same path as others.

“APOE4 seems to have a seeding effect,” Schindler said. “At very low levels, below the critical point, you will see an increase in amyloid in patients with APOE4, while people without APOE4 have no change. This means that APOE4 traders will reach the critical point sooner. Having two People with APOE4 copies reach the tipping point about 10 years earlier than those without copies. But after that, we don’t see any difference between APOE4 operators and non-operators.”

Out-of-pocket costs are approximately US$6,000, and amyloid PET brain scans are too expensive for routine clinical use. However, the algorithm can help accelerate the pace of drug development by accelerating clinical trials.

“Most participants in clinical trials designed to prevent or delay symptoms of Alzheimer’s disease will not experience symptoms during the trial,” Schindler said. “For participants and researchers, this requires a lot of time and effort, but it does not produce useful data. If we can only conduct trials in people who may develop symptoms in the next few years, it will make it easier to find a treatment. The process is more effective.”

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