Stanford scientists find resting brain activity could predict Alzheimer’s disease years before memory decline: ScienceAlert

Today, two people can get the same score on a memory test. Years later, one may start missing appointments and struggling to complete daily tasks while the other still manages both with ease.

A first clue to this difference could lie in a brain scan, research suggests.

In a new study, Stanford Medicine researchers and their colleagues wanted to know if the way brain regions work together at rest could reveal who was most likely to have memory problems years later.

To figure out what to look for, they started with two groups whose memory abilities were already quite different.

One group included 110 people with Alzheimer’s disease. The other included 180 adults who were at least 75 years old and performed better on memory tests than is typical for middle-aged adults.

Researchers call people with this type of exceptional memory later in life SuperAgers.

The team looked at scans taken while participants were still. The technique, called functional MRI, tracks changes in blood oxygen as an indirect measure of brain activity. The researchers looked for regions whose signals rose and fell simultaneously.

Some connections involving the front of the brain were stronger in SuperAgers. Some involving the insula, a region deep in the brain, were stronger in people with Alzheimer’s disease.

“This suggests that Alzheimer’s vulnerability may be reflected in the way the brain functions as an interconnected system,” Kanhao (Alex) Zhao, a postdoctoral researcher specializing in computational neuroscience at Stanford Medicine and lead author of the study, told ScienceAlert.

The team used these models to develop the Alzheimer’s Disease Resilience-Vulnerability Connectome, or ARC.

“The ARC score summarizes whether an individual’s brain connectivity is more like that of SuperAgers, who retain exceptional memory into old age, or that of individuals with Alzheimer’s disease,” Zhao said.

Lower scores were more like SuperAger and higher scores were more like Alzheimer’s. When the researchers tested the method on a separate set of scans from 143 people already in one of these two groups, about 71 percent of them were placed in the correct group.

The next step brought the team back to their original question. Could the same score tell them something about the future of people whose memory and thinking skills were still intact?

Researchers calculated ARC scores from the first exams of 1,315 adults without cognitive impairment and compared them to test results and clinical assessments from later years. Most datasets spanned about five to six years, and the longest spanned 12 years.

Initially, people with lower and higher ARC scores performed similarly on most tests. Over time, people who had more Alzheimer’s tests declined more quickly in assessments of memory and daily functioning.

They were also more likely to develop Alzheimer’s disease or mild cognitive impairment, which can make problems with memory or thinking noticeable while people can still manage most of their daily activities on their own.

People who underwent more SuperAger-type analyzes were on average younger. To see how much this age difference could explain, the researchers performed additional analysis on a dataset. Differences in clinical assessments and test performance persisted after accounting for age at baseline.

Follow-up scans also showed that beta-amyloid, a protein that can build up in plaques in the brain, accumulated more quickly in people with more Alzheimer’s-like scans, even though the groups started with similar levels. The researchers found no clear difference in the accumulation of tau, another protein linked to Alzheimer’s disease.

The addition of ARC improved predictions about who would develop mild cognitive impairment or Alzheimer’s disease beyond what researchers could predict using age, analyzes measuring amyloid beta and tau, and genetic risk related to the APOE gene. If the results hold up, the score could help researchers recruit people at higher risk into Alzheimer’s disease prevention trials before memory problems appear.

“We would need larger prospective studies following cognitively healthy individuals over several years, with validation across diverse populations and MRI machines,” Zhao said.

“These studies should establish reliable predictions at the individual level, demonstrate added value beyond existing biomarkers, and determine whether ARC-based assessments improve clinical decisions. »

The research was published in Scientific advances.