Objective: To employ Magnetic Resonance Imaging (MRI) and investigate structural pathology in the cortex of Glucocerebrosidase (GBA) gene mutation carriers.

Background: Mutations in the GBA gene are a risk factor for Parkinson’s disease (PD). Carriers of GBA mutations who develop PD may present with anxiety before the development of overt symptoms. The pathophysiology underlying anxiety in GBA mutation carriers is unknown.

Method: The Parkinson’s Progression Markers Initiative database was utilised to identify 86 asymptomatic GBA mutation carriers and 37 GBA mutation carriers with PD (GBA-PD). Presence of anxiety was assessed with the State Trait Anxiety Inventory (STAI), a clinical scale for anxiety divided into state (STAI-s) and trait (STAI-t) subscales. A cut-off of ≥40 was used to identify participants with anxiety. Structural MRI was used to assess volumetric changes in cortical and subcortical areas, and cortical thickness. Differences between groups were assessed with Student’s t test with correction for False Discovery Rate. Pearson’s partial correlation was used to assess relationships between structural alterations in regions associated with anxiety and clinical characteristics.

Results: Anxiety was present in 31.4% of unaffected GBA mutation carriers, and 16.2% of GBA-PD. Unaffected GBA carriers with anxiety, showed increased thickness in the lingual gyrus (2.01±0.09 vs 1.96±0.11, P=0.046) and in the paracentral gyrus (2.3±0.18 vs 2.22±0.18, P=0.04). GBA-PD with anxiety, showed decreased volumes in Substantia Nigra compared with GBA-PD without anxiety (0.53±0.05 vs 0.65±0.02, P=0.01); and thinning of the paracentral gyrus (2.1±0.14 vs 2.27±0.15, P=0.02). In the unaffected GBA population, increased thickness of the lingual gyrus correlated with the severity of anxiety (r= -0.41, P=0.035).

Conclusion: These results suggest that presence of anxiety in GBA mutation carriers is associated with pathology affecting the cortical structure. The increased thickness of areas associated with anxiety in unaffected GBA carriers may reflect early compensatory changes.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/cortical-pathology-in-glucocerebrosidase-mutation-carriers-with-anxiety-an-mri-study/