Neural correlates of anxiety symptoms in mild Parkinson's disease: A prospective longitudinal voxel-based morphometry study

Abstract

Background

Anxiety is prevalent in patients with Parkinson's disease (PD) and may affect patients' quality of life. Yet, little is known about the neural basis of anxiety in PD, and none have used a longitudinal design.

Methods

73 patients with mild PD were recruited and followed up for 18months. A whole-brain analysis was first used to identify brain regions associated with anxiety symptoms, followed by a regional analysis focusing on a priori hypothesised regions at baseline. A multivariate generalized estimating equations analysis was then conducted to determine the longitudinal association between grey matter (GM) volumetric changes of these significant regions and changes of anxiety symptoms.

Results

At baseline, anxiety symptom severity was associated with decreased GM volumes in the bilateral precuneus and anterior cingulate cortex (ACC). Over 18months, increased severity of anxiety symptoms was associated with decreased GM volume in the left precuneus and ACC, independent of age, gender, education, depressive symptom severity or use of psychiatric medication.

Conclusions

These results mainly implicate the precuneus and ACC in the pathogenesis of anxiety in PD. We speculate that these structural changes could reflect the disrupted default mode network due to PD pathology, contributing to spontaneous anxiety-related self-focused thoughts.