A Tipping Point for Amyloid Accumulation in the Development of Alzheimer's Disease

Researchers here report on their view of amyloid accumulation in the brains of older people, as established by PET scans. They suggest that there is a tipping point after which further accumulation and the consequent development of Alzheimer's disease becomes predictable. It is interesting to consider what is going on under the hood to produce this behavior. Most aspects of age-related disease involve mutual interactions between different processes of damage and dysfunction, leading to feedback loops that change behavior at different stages of disease progression. In a system in which there is some capacity for maintenance, there may well be thresholds of damage and dysfunction after which maintenance cannot keep up, and pathology develops more rapidly as a result.

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 now an algorithm developed by researchers represents a new way of analyzing 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.

Researchers analyzed amyloid PET scans from 236 people participating in Alzheimer's research studies. 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 4½ 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.

Researchers 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 they 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. 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."

Link: https://medicine.wustl.edu/news/time-until-dementia-symptoms-appear-can-be-estimated-via-brain-scan/

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