Detecting dementia’s damaging effects before it’s too late

Summary: Using MEG neuroimaging, researchers identify abnormalities in functional activity in brain regions which look structurally normal on conventional MRI scans. The findings could help with early detection of primary progressive aphasia.

Source: University of Arizona

Scientists might have found an early detection method for some forms of dementia, according to new research by the University of Arizona and the University of Toronto’s Baycrest Health Sciences Centre.

According to the study published in the journal Neuropsychologia last month, patients with a rare neurodegenerative brain disorder called Primary Progressive Aphasia, or PPA, show abnormalities in brain function in areas that look structurally normal on an MRI scan.

“We wanted to study how degeneration affects the function of the brain,” said Aneta Kielar, the study’s lead author and assistant professor in the UA Department of Speech, Language and Hearing Sciences.

But what she and her team discovered was that the brain showed functional defects in regions that were not yet showing structural damage on MRI.

Structural MRI provides 3D visualization of brain structure, which is useful when studying patients with diseases that literally cause brain cells to wither away, like PPA.

Magnetoencephalography, or MEG, on the other hand, “gives you really good spatial precision as to where the brain response originates. We want to know if the decreased brain function is coming from the areas that are already atrophied or areas in an earlier stage of decline,” said Jed Meltzer, the study’s senior author and an assistant professor of psychology at the University of Toronto.

Kielar and her colleagues compared brain scans of patients with PPA to healthy controls while both groups performed language tasks. The researchers also imaged participants’ brains while at rest. The functional defects were related to worse performance in the tasks, as individuals with PPA lose their ability to speak or understand language while other aspects of cognition are typically preserved.

Identifying the discrepancy between a PPA brain’s structural and functional integrity could be used as an early-detection method.

This is promising because “many drugs designed to treat dementia are proving to be not really affective and that might be because we’re detecting the brain damage too late,” Kielar said. “Often, people don’t come in for help until their neurons are already dead. We can do compensation therapies to delay disease progress, but once brain cells are dead, we can’t get them back.” This technique could allow patients to get ahead of the damage.

This is a brain scan of someone with PPA
This image highlights areas in a PPA-affected brain during a language task where researchers observe functional abnormality (green) and structural degenerating (yellow). The green areas may be at-risk or dysfunctional, even if the neurons are not dead yet. The image is credited to Aneta Kielar.

Kielar acknowledged that this was a small study, which is partially because PPA is such a rare form of dementia, and that further investigation is needed.

Next, she hopes to uncover why this structural and functional mismatch is happening in PPA brains.

“It’s interesting that the affected areas are so far from the neurodegeneration,” Kielar said. “One reason this might be happening is that those areas could be connected with white matter tracts,” which facilitate communication between different brain regions. “When one area is dead, the area connected to it doesn’t get normal input. It doesn’t know what to do, so it starts to lose its function and atrophy because it doesn’t get stimulation.”

Funding: This study was supported by the Ontario Brain Institute Ontario Neurodegenerative Disease Research Initiative, an Alzheimer’s Association New Investigator Research Grant (NIRG-12-236224) and a postdoctoral research award from the Ontario Research Coalition (ORC).

About this neuroscience research article

Source:
University of Arizona
Media Contacts:
Mikayla Mace – University of Arizona
Image Source:
The image is credited to Aneta Kielar.

Original Research: Closed access
“Slowing is slowing: Delayed neural responses to words are linked to abnormally slow resting state activity in primary progressive aphasia”. Aneta Kielar, Priyanka P. Shah-Basak, Tiffany Deschamps, Regina Jokel, Jed A. Meltzer.
Neuropsychologia. doi:10.1016/j.neuropsychologia.2019.04.007

Abstract

Slowing is slowing: Delayed neural responses to words are linked to abnormally slow resting state activity in primary progressive aphasia

Neurodegenerative disorders are often characterized by neuronal “slowing,” which may be assessed in different ways. In the present study, we examined the latency of neural responses to linguistic stimuli in participants diagnosed with primary progressive aphasia (PPA), as well as changes in the power spectra of resting state activity, both measured with MEG. Compared to both age-matched and younger controls, patients with PPA showed a delayed latency of 8–30 Hz event-related desynchronization (ERD) in response to semantic anomalies. In addition, resting-state MEG revealed increased power in the lower frequency delta and theta bands, but decreased activity in the higher alpha and beta bands. The task-induced and spontaneous measures of neural dynamics were related, such that increased peak latencies in response to words were correlated with a shift of spontaneous oscillatory dynamics towards lower frequencies. In contrast, older controls showed similar task related ERD latencies as younger controls, but also “speeding” of spontaneous activity, i.e. a shift towards faster frequencies. In PPA patients both increased peak latencies on task and increased slow oscillations at rest were associated with less accurate performance on the language task and poorer performance on offline cognitive measures, beyond variance accounted for by structural atrophy. A mediation analysis indicated that increased theta power accounted for the relationship between delayed electrophysiological responses and reduced accuracy in PPA patients. These results indicate that the neuropathological changes in PPA result in slowing of both task-related and spontaneous neuronal activity, linked to functional decline, whereas the speeding of spontaneous activity in healthy aging seems to have a protective or compensatory effect.

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