Objective: To determine whether structural changes in the hippocampus and amygdala are associated with anxiety in Parkinson’s disease (PD), and to identify whether these alterations are also present in anxious healthy controls (HC).

Background: Anxiety is one of the most common non-motor symptoms in PD, affecting approximately 1/3 patients, often reporting anxiety as being as incapacitating as motor symptoms. Despite its neurological basis being poorly understood, limbic structures involved in emotion regulation and fear circuits, such as the hippocampus and amygdala, are vulnerable to PD. Hippocampal subfield alterations have previously been linked to neuropsychiatric symptoms, however, these regions have not been investigated in anxious PD cohorts.

Method: 90 subjects included in this study were split into four groups: PD with anxiety (PDA; n=21), PD without anxiety (PDN; n=24), HC with anxiety (HCA; n=20) and HC without anxiety (HCN; n=25). High resolution T1 scans were performed on a 3T MRI, and segmentation of the hippocampus was done using Freesurfer. Regions of interest (ROIs) selected for analysis focused on the amygdala, and hippocampal subfields implicated in limbic processing (CA1, CA2/3, fimbria and hippocampus-amygdala transition area (HATA)). ROI volumes were analysed using ANCOVAs, controlling for age, sex and TIV. Correlation analyses investigated the relationship between anxiety severity and ROI volume.

Results: In comparison to the PDN group, the PDA group showed reduced volume of the right fimbria, as well as enlargement of the right HATA. In comparison to the HCA group, the PDA group revealed bilateral atrophy of the fimbria, alongside volume reductions in the right HATA. Volumetric differences were not observed between HC groups, or PDN and HCN groups. Correlations in the PD cohort exhibited significant associations between greater anxiety severity and volume reductions in the left fimbria and left HATA. Correlations in the HC cohort revealed significant associations between longer anxiety duration and volume reductions in the right CA2/3, left amygdala and bilateral CA1.

Conclusion: These findings demonstrate that there is a distinct pattern of limbic system alterations in anxious PD patients. Since no such findings were seen in anxious HCs, we can determine that these alterations are specific to PD, reinforcing anxiety as a phenotype of the disease, further validating patient experiences.

Hippocampal Subfield Segmentation [1]

PD Correlations: Anxiety Severity vs. ROI Volume

References: 1. Zheng F, Cui D, Zhang L, et al. The volume of hippocampal subfields in relation to decline of memory recall across the adult lifespan. Front Aging Neurosci. 2018;10(OCT). doi:10.3389/fnagi.2018.00320

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MDS Abstracts - https://www.mdsabstracts.org/abstract/investigating-hippocampal-subfield-and-amygdala-volumes-in-parkinsons-disease-with-anxiety/