Brain activity at rest may provide clues to the diagnosis and progression of Alzheimer’s disease

A study from the University of Michigan and Columbia University has shown that frequent reorganisation of brain networks – known as neural flexibility – is greater in people with Alzheimer’s disease and may predict which healthy individuals are at risk of developing the condition years before diagnosis

Some regions of the brain in people with Alzheimer’s disease reorganise more frequently while at rest than in people without the condition, and in healthy individuals this pattern sometimes predicted later onset of the disease, according to a study from the University of Michigan and Columbia University.

“Our brain is always organising and reorganising regions into different functional networks in order to make sure it has the resources it needs to complete a variety of cognitive tasks,” said Dr. Eleanna Varangis, assistant professor at the University of Michigan School of Kinesiology and first author of the study.

The ability of the brain to reorganise its regions is known as neural flexibility.

“We found that in Alzheimer’s disease the brain tends to reorganise more frequently. Overall, our paper suggests that we can use information about the way our brain organises into functional networks to possibly help identify whether or not someone has Alzheimer’s disease.”

It is thought that more than one in ten men and one in five women will develop Alzheimer’s disease in their lifetime and early intervention is regarded as critical to preserve independence. Functional brain imaging has shown promise as an early biomarker of disease risk, Varangis noted.

In the study the researchers used functional magnetic resonance imaging (MRI) data collected while participants were awake but resting to examine neural flexibility. The data covered 862 older adults in the Alzheimer’s Disease Neuroimaging Initiative, across three groups: cognitively normal; mild cognitive impairment; and those with Alzheimer’s disease. The work was supported by the US National Institutes of Health and the Brain & Behavior Research Foundation.

The researchers set out to establish whether the damage caused by Alzheimer’s disease altered neural flexibility and whether the measure could predict which participants in the cognitively normal group would later develop Alzheimer’s disease. They found that neural flexibility was significantly higher in the Alzheimer’s disease group than in the cognitively normal group across all brain regions and in six specific networks. Neural flexibility was also significantly higher in the mild cognitive impairment group than in the cognitively normal group in the visual network.

Among the 617 healthy participants at baseline, 8.6 per cent developed dementia over the following 11 years, in line with national estimates of dementia prevalence in older age. Higher neural flexibility in the visual network was associated with progression to Alzheimer’s disease.

“While this was only a modest effect, it is a good hint that activity in these visual regions may be telling us something about risk for Alzheimer’s disease years before formal diagnosis,” said Varangis.

“Since we think of cognitive impairment being the primary symptom of Alzheimer’s disease, the finding that this sensory network was the one that predicted Alzheimer’s conversion was a bit unexpected, but it was not necessarily surprising.

“In typical Alzheimer’s disease, the brain pathology that causes the condition does not progress to sensory regions until later stages. It could be that these regions show more flexibility because they are among the healthier regions of the brain that have not yet been affected by Alzheimer’s disease pathology,” she added.

The results challenged the researchers’ initial expectations. Flexibility and adaptability are usually regarded as beneficial traits, but the evidence suggested otherwise.

“Once we see the disease process setting in, it could be the case that if we are just resting and we are showing this frequent reassignment of brain regions to different functions, it could be that parts of the brain are not working the way that they should be,” Varangis said, emphasising that the work remained experimental.

“The positive [thing] here is that a lot of people think that in neurodegenerative disease you see this general brain slowing over time. But to me, these findings also speak to the fact that the brain is such a dynamic organ, that even when people are experiencing these cognitive changes or getting worse over time, there is so much flexibility for our brains to adapt, which is also a sign of hope and resilience.”

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