Dementia affects more than just memory; it also alters behavior and mental well-being. Recent research indicates a link between the brain’s salience network and tau protein in these changes.
Memory loss is often the first thing that comes to mind when people think about dementia, including Alzheimer’s disease.
However, dementia impacts behavior too, leading to increased irritability or distress, depression, anxiety, apathy, or even a significant personality shift.
These behavioral shifts can significantly disrupt an individual’s life, much like cognitive and memory decline.
A new study by researchers at the University of Michigan has uncovered interesting insights into how the brains of those showing early signs of dementia-related behavioral changes might function.
By employing advanced imaging techniques on the brains of 128 individuals in the early stages of dementia, they established connections between a vital communication network in the brain, a protein known as tau, and the severity of behavioral symptoms.
This expands upon previous knowledge of tau’s role in advanced dementia, where it contributes to tangled nerve fibers in areas associated with cognition and memory.
The latest findings suggest that tau may compromise the functionality of the brain’s salience network. This crucial network connects specific brain regions and plays a significant role in interpreting and responding to environmental stimuli, as well as managing thoughts and emotions.
The researchers found that greater disruption in a person’s salience network linked to tau presence resulted in more pronounced behavioral changes. Their findings are published in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.
While the one-time imaging conducted on these 128 participants is not able to establish direct cause-and-effect relationships, the observed strong correlation between tau levels, salience network disruption, and behavioral modifications is compelling, according to the research team.
They urge for additional studies to examine this correlation in different groups and for research that tracks changes over time to understand how the interconnected brain cell pathways within the salience network deteriorate and relate to tau accumulation and behavioral shifts over the years.
Additionally, they aspire to investigate whether they can mitigate behavioral changes in individuals with early-stage dementia by stimulating the salience network using mild electrical currents or magnetic fields applied externally, aided by precise imaging.
For more information on how individuals can participate in their research, details are available here.
The research team, part of the Research Program on Cognition and Neuromodulation-Based Interventions (RP-CNBI), is led by Alexandru D. Iordan, Ph.D., and program leader Benjamin M. Hampstead, Ph.D., both associated with the U-M Medical School’s Department of Psychiatry.
Iordan, the lead author of the study, states, “We see that tau pathology relates to behavioral symptoms indirectly, via the dysfunction of the salience network; greater impairment to this network correlates with heightened severity of behavioral symptoms.”
He adds, “This is the first study linking an individual’s biomarker status to dysfunction in the salience network and associated behavioral symptoms within the Alzheimer’s disease spectrum.”
Methods of Brain Imaging
The research team utilized functional magnetic resonance imaging (fMRI) to analyze each participant’s brain and to identify three distinct networks that interconnect various parts of the brain. They employed a measure known as the network segregation index to assess the functional independence of each network in relation to the others.
They coupled fMRI results with data from a series of neuropsychological assessments and behavioral questionnaires completed by the volunteers. They also examined outcomes from positron emission tomography (PET) scans to determine the presence of excess tau protein and beta amyloid, another protein linked to Alzheimer’s.
The only network whose integrity was correlated with tau presence and the severity of dementia-related behavioral issues was the salience network. While the default-mode network acted as a supporting player, the third network investigated, referred to as the frontoparietal network, did not show a link to behavioral symptoms.
The study indicated that, unlike tau, the mere presence of amyloid in some participants’ brains was not related to the functionality of the salience network or their level of behavioral symptoms.
Iordan points out that the salience network is also known to be involved in certain psychiatric conditions and in frontotemporal dementia, which primarily features swift behavioral and personality changes.
Opportunities for Biomarker and Neuromodulation Applications
Iordan notes that PET scans for tau and amyloid are already being used in clinical environments to diagnose dementia and guide treatment strategies aimed at reducing amyloid buildup to slow cognitive decline.
Additionally, blood tests detecting tau and amyloid are emerging as potential biomarkers for dementia risk, which are significantly more affordable than PET scans, possibly paving the way for future research into tau’s role in behavioral changes.
Further research may also elucidate and possibly predict differences in the emergence of behavioral changes in individuals with dementia, alongside the rate of cognitive decline. This might also contribute to identifying those whose behavioral shifts are the earliest indicators of dementia risk, even before cognitive changes manifest.
But what excites Iordan and his team the most?
“Our findings present a functional target for potential intervention,” he stated. “We are soon expected to see if brain stimulation influences these relationships, thanks to a larger study led by Dr. Hampstead evaluating the effects of different levels of mild electrical currents applied to the brain. This larger study is nearing its conclusion, and we are eager to observe the results, so stay tuned!”
Researchers at RP-CNBI, under Hampstead’s direction, utilize neuropsychological assessments, various forms of neuroimaging, electrical and magnetic brain stimulation, along with rehabilitation methods, to develop and implement non-drug therapies for Alzheimer’s disease and related dementias.
