Objective: To compare structural differences in brain magnetic resonance imaging (MRI) between Glucocerebrosidase (GBA) mutation carriers with Parkinson’s disease (PD-GBA) vs non-mutation carriers.

Background: PD-GBA patients who undergo subthalamic nucleus (STN) deep brain stimulation (DBS) may have accelerated cognitive decline compared to non-mutation carriers. In addition to its motor circuitry, the STN also has limbic and associative projections, which are thought to impact cognition and mood. In this study, we sought to compare structural differences in brain regions involved in STN limbic and cognitive circuitry between PD-GBA and non-mutation carriers.

Method: PD-GBA patients who underwent 3T brain MRI during work-up for DBS consideration at Rush University were included in the study, and controls were Parkinson’s disease (PD) DBS candidates without GBA mutation and were matched 1:1 by sex and age. We analyzed brain regions involved in STN limbic and associative circuitry including anterior cingulate, prefrontal cortex, orbitofrontal cortex, hippocampus, amygdala and others. Volumetric analysis was performed using FreeSurfer software. We compared group differences in normalized brain region volume and asymmetry index using mann-whitney test, and linear regression was performed amongst PD-GBA patients to assess asymmetry index with baseline cognitive function. p-value < 0.05 was considered significant.

Results: Ten PD-GBA patients and 10 non-carrier controls were included in the study. Baseline characteristics were similar. There was no difference in normalized brain region volume between the two groups, however asymmetry index of ventrolatral prefrontal cortex (vlPRF) in PD-GBA vs PD non-GBA patients was -0.03 +/- 0.04 vs -0.001 +/- 0.05, respectively (p=0.1), though our study was under-powered to detect significant difference. In PD-GBA patients, there was a moderate correlation between mean asymmetry index of vlPFC and baseline cognitive function (r=0.73, p=0.016).

Conclusion: Structural differences in brain regions involved with STN limbic and associative circuitry may explain some of the cognitive differences between PD-GBA and non-mutation carriers.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/structural-mri-features-of-glucocerebrosidase-gba-associated-parkinsons-disease/