Understanding behavioral changes in early dementia

When most people think of dementia, including Alzheimer’s disease, they probably first think of memory loss.

But dementia also changes the way a person behaves, whether they become easily angry or sad, become depressed, anxious or apathetic, or even change their entire personality.

Over time, these behavioral changes can be as disruptive to their lives as losing their ability to think clearly or remember.

Now, a team of researchers from the University of Michigan reports new clues about what might be happening in the brains of people who experience even the first signs of dementia-related behavioral changes.

Using two types of advanced medical imaging to study the brains of 128 people in the early stages of dementia, they show links between one of the brain’s most crucial communication networks, a protein called tau, and the level of behavioral symptoms that affect person has.

This goes beyond the role scientists already know tau plays in people with more advanced dementia: causing tangled nerve fibers in brain areas involved in thinking and memory.

The new study suggests that tau disrupts the integrity of the brain’s salience network. This highway of connections between specific areas of the brain is key to our ability to understand things happening around us and decide how to respond to them. It also helps us process our own thoughts and emotions.

The researchers showed that the more a person’s salience network was disrupted in the presence of tau, the more behavioral changes that person would experience. They report their findings Alzheimer’s and Dementia: The Journal of the Alzheimer’s Association.

Although the one-time imaging of these 128 study volunteers cannot demonstrate cause and effect, the strong association between tau, salient network disruption and behavioral change is intriguing, the team says.

They call for further research into the potential connection in other populations, and for research to evaluate changes over time, to investigate what might be going on in the pathways of connected brain cells that make up the salience network , and to investigate how this relates to tau buildup. and behavioral changes over the years.

They also hope to test whether they can slow behavioral change in people with early-stage dementia by targeting the salience network with mild electrical currents or magnetic fields applied from outside the skull and guided by precise imaging.

More information on how individuals can learn more about opportunities to participate in their research can be found here.

The researchers, from the Research Program on Cognition and Neuromodulation Based Interventions (RP-CNBI), are led by Alexandru D. Iordan, Ph.D. and program director Benjamin M. Hampstead, Ph.D. Both are faculty members in the Department of Psychiatry at the UM Medical School.

Iordan, a neuroscientist who is lead author of the new study, says: ‘What we see is that the presence of tau pathology is linked to behavioral symptoms, not in a direct relationship, but rather through dysfunction of a specific network in the brain –; the salience network. The more this network is affected, the more severe the behavioral symptoms.

This is the first study to link an individual’s biomarker status to the dysfunction of this network and behavioral symptoms in people on the Alzheimer’s disease spectrum.”

Alexandru D. Iordan, Ph.D., neuroscientist, lead author

Two types of brain imaging

The team used functional magnetic resonance imaging (fMRI) to study each volunteer’s brain and trace three different networks, each connecting remote areas of the brain. They used a metric called the network segregation index to measure how functionally independent each network was from other brain networks.

They combined fMRI findings with results from a series of neuropsychological tests and behavioral questionnaires that the volunteers took. They also looked at the results of positron emission tomography, or PET, scans that showed whether the person’s brain contained an excess of tau protein, as well as beta-amyloid, another Alzheimer’s-related protein.

The salience network was the only one of the three networks whose integrity level correlated with the presence of tau and the severity of dementia-related behavioral problems. The default-mode network seems to be involved as a supporting player. The third network examined, called the frontoparietal network, was not related to behavioral symptoms.

The new study showed that, unlike tau, the presence of amyloid alone in the brains of some volunteers was not linked to salience network problems or related to that person’s level of behavioral symptoms.

Iordan notes that the salience network is also known to be involved in some psychiatric disorders and in frontotemporal dementia, a form of early-onset, rapidly progressive dementia characterized primarily by behavioral and personality changes.

Potential for use of biomarkers and neuromodulation

Iordan notes that PET scans for tau and amyloid are now being used clinically in the diagnosis of dementia and in the management of treatment with new medications that aim to reduce amyloid buildup, with the aim of slowing cognitive decline.

But blood tests have also become available that can also detect the presence of tau and amyloid and use them as biomarkers of dementia risk. Because they are much cheaper than PET scans, they could also be useful in future studies of the role of tau in behavioral changes, he says.

Further research could also help explain and even predict the variation in the onset of behavioral changes in people with dementia, and the rate of decline. It could also lead to ways to identify people whose behavioral changes are the earliest observable sign of dementia risk, even before cognitive skills change.

But the most exciting thing for Iordan and his colleagues?

“Our findings provide us with a functional target for potential intervention,” he said. “We will soon be able to see whether brain stimulation changes these relationships thanks to a larger study led by Dr. Hampstead that evaluates the effects of different doses of weak electrical currents applied to the brain. This larger study is nearing completion, and we’re excited to see what the results show, so stay tuned!”

Researchers at RP-CNBI, led by Hampstead, use neuropsychological tools, various types of neuroimaging, electrical and magnetic brain stimulation, and rehabilitation techniques to develop and apply non-drug treatments for Alzheimer’s disease and related dementias.