Dementia is the universal term to describe memory loss that also detrimentally affects language, problem-solving, and other mental faculties to interfere with daily life. To date, Alzheimer’s disease (AD) is the most widespread cause of dementia – diagnosed using multiple reviews of the patient’s medical history, a physical examination, laboratory tests, and observing the day-to-day behavior of the subject.

Unfortunately, it is not possible to use just one diagnostic test to determine if someone has AD. However, biochemical and genetic data suggest that beta-amyloid may be one of the most important markers in this disease. In those who eventually develop AD, amyloid stealthily accumulates in the brain for up to twenty years before the first signs of confusion and forgetfulness appear.

Various neuroimaging can also be used to diagnose and monitor Alzheimer’s disease. Among these is the widely used amyloid positron emission tomography (amyloid-PET), which assesses brain amyloid deposition. Amyloid PET is a non-invasive neuroimaging technique that visualizes the accumulation of fibrillar amyloid-beta in the living human brain with histopathological confirmation.

Now, researchers at Washington University have developed an algorithm used with amyloid PET that correctly estimated when study participants would start to show signs of Alzheimer’s disease – even those that presented with no cognitive symptoms. The team states their algorithm uses data from a brain scan known to gauge brain levels of the key Alzheimer’s protein amyloid-beta. It is in this way they can predict when symptoms will start. The study is published in the journal Neurology.

Previous studies show the formation of beta-amyloid in the central nervous system is one of the two main hallmarks of Alzheimer’s disease; the other is tangles. Amyloid PET works by detecting beta-amyloid in the plaques and blood vessels found in the brain. Consequently, as these plaques are present in all patients with AD, it is theorized that beta-amyloid plays a vital role in the disease.

Presently, the most reliable marker to exclude the possibility of AD is the lack of amyloid-beta in an Amyloid PET scan. A positive amyloid-beta diagnosis is known to be affected by age and APOE4, the most significant genetic-based risk factor for AD. An emerging technique, amyloid PET, is predicted to uncover the details of the early stages of AD, with the hope this will lead to the development of effective therapies and prevention strategies.

The current study develops an algorithm that can predict when signs of AD will manifest in individuals with no cognitive symptoms. The algorithm projects how far a person has progressed toward dementia using their age and a single amyloid PET scan; it can also estimate how much time is left before cognitive impairment begins.

The researchers accessed over 1,300 clinical assessments performed every one to three years on 180 participants to verify their data. At the start of the study, most participants were cognitively normal, with repeated assessments allowing the researchers to pinpoint when each participant’s cognitive skills began to slip.

Their algorithm allowed the lab to observe that amyloid accumulation has a tipping point that each individual hits at a different age. After this, amyloid accumulation follows a reliable trajectory. Senior author Suzanne Schindler, MD, Ph.D., interjects: “You may hit the tipping point when you’re 50; it may happen when you’re 80; it may never happen,” She goes on to that “…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.”

Data shows that participants who reached the tipping point at younger ages took longer to develop cognitive symptoms than those who arrived at the tipping point later in life. Subsequently, patients who hit the tipping point at age 50 typically took nearly twenty years to develop symptoms; those who hit it at age 80 took less than ten years. Regarding participants presenting with the genetic variant APOE4 – they hit the tipping point younger, but once past that point, they followed the same trajectory as everyone else.

An added advantage, this new technique requires just one brain scan, plus the person’s age, to estimate the time to symptom onset.

In the future, the researchers say that amyloid PET brain scans are too costly for regular use. However, their algorithm could help accelerate drug development so that expense is no longer an issue.

Source: Washington University School of Medicine

Image courtesy of Freepik

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