Patterns of Brain Atrophy Line Up With Protein’s Damaging Spread

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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In people with Parkinson’s disease, patterns of brain atrophy over time are consistent with patterns of alpha-synuclein spreading through the brain, an imaging study in patients suggests.

The study, “Regional changes of brain structure during progression of idiopathic Parkinson’s disease – A longitudinal study using deformation based morphometry,” was published in Cortex.

Parkinson’s is a progressive neurodegenerative disease, marked by atrophy over time in certain regions of the brain. However, the exact patterns of brain atrophy over time, and how they associate with disease symptoms, remains incompletely understood.

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To learn more, scientists in Germany conducted MRI brain imaging of 37 people with Parkinson’s, as well as 27 adults without the disease as a control group.

At baseline (the study’s start), participants’ average age was in the mid-50s, and patients’ average disease duration was just under four years. Brain scans were conducted at various points in time for up to 8.8 years, with an average follow-up time of 3.7 years.

Results showed that several brain regions were markedly smaller in Parkinson’s patients at baseline, including parts of the motor cortex (which helps to control movement) and the somatosensory cortex (which helps the brain interpret sensations like temperature and pain).

A few brain regions were larger in patients, which the researchers suggested is likely because these regions were trying to compensate for damage elsewhere in the brain early in the disease’s course.

Over time, rates of brain atrophy were significantly higher in people with Parkinson’s than those without it. Average rates of whole brain volume decrease were .33% per year in Parkinson’s patients, compared to .14% each year in controls.

This decline mainly affected grey matter, the specific parts of brain tissue that houses the bodies of nerve cells. White matter — brain tissue that mainly contains connections between nerve cells — was comparatively less affected.

Brain regions that showed especially pronounced atrophy over time in Parkinson’s included the temporal lobe (which helps process sounds and encode memory), the parietal lobe (which helps process sensory information), and the frontal lobe (which helps control cognition and emotion).

“Our study provides detailed in vivo [in living people] data about how the brain of Parkinson’s disease patients degenerates across space and time,” Peter Pieperhoff, the study’s first author with Research Centre Jülich, said in a press release.

During the study, participants underwent a number of standardized assessments of symptom severity, life quality, and cognitive status. Analyses indicated that worse scores were generally associated with more volume loss in certain brain regions, including the amygdala that helps to regulate emotion.

Broadly, this finding “suggests that worse clinical scores were associated with reduced region volumes,” the researchers wrote, though they cautioned that it is difficult to draw cause-and-effect conclusions from this small study, and stressed that the associations were statistically only moderate in strength.

Still, these findings provide a “map” of how brain deterioration tends to occur over time in Parkinson’s disease.

Notably, the researchers said that the patterns of brain atrophy observed here line up quite strongly with a staging system for Parkinson’s disease first proposed in 2003. Its supporting study had been conducted by analyzing patterns of alpha-synuclein — a protein that forms toxic clumps to drive Parkinson’s — in donated brains. The most pronounced brain atrophy was observed in regions predicted to have the most alpha-synuclein accumulation in that study.

“The longitudinal in-vivo pattern of accelerated atrophy in brains of PD [Parkinson’s disease] patients was highly similar to the propagation of [alpha-synuclein]-pathology in PD,” the scientists concluded.