# Longitudinal faster anxiety progression of GBA variant carriers in the early Parkinson’s disease cohort

## TL;DR

People with Parkinson’s disease who carry GBA gene variants experience faster worsening of anxiety symptoms over time.

## Contribution

This study shows that GBA variant carriers in early Parkinson’s disease have accelerated anxiety progression.

## Key findings

- GBA variant carriers had a faster annual increase in anxiety scores compared to non-carriers.
- Higher baseline autonomic dysfunction scores predicted faster anxiety progression.
- The combination of GBA variants and autonomic dysfunction led to the most severe anxiety worsening.

## Abstract

Anxiety symptoms are prevalent neuropsychiatric manifestations in Parkinson’s disease (PD) and impact the development of motor complications. Our aim was to evaluate the association of GBA variants with the anxiety development in early PD cohort.

This cohort study used data from the Parkinson Progression Marker Initiative. The primary outcome anxiety was assessed by State–Trait Anxiety Inventory (STAI). The association between GBA and longitudinal change in the STAI total score was examined using linear mixed-effects model, and the association between GBA and anxiety progression was examined using Cox survival analysis.

A total of 385 patients with PD were included in this study, 39 of them were GBA variant carriers and 346 were idiopathic PD without GBA variants. Patients with GBA variants had faster annual increase in anxiety score (β = 0.44; 95% CI, 0.18 to 0.71; p < 0.001) and were at higher risk of anxiety progression (HR 1.87; 95% CI, 1.03 to 3.41; p = 0.03,). Higher baseline scores for Scales for Outcomes in Parkinson’s Disease-Autonomic (SCOPA-AUT), which indicated the autonomic dysfunction, also independently predicted faster increase in anxiety score (β = 0.48; 95%CI, 0.19 to 0.69; p < 0.001) and higher incidence of anxiety development (HR = 1.05; 95% CI, 1.01 to 1.08; p = 0.008).

These findings suggest that longitudinal anxiety symptoms worsening was faster in PD patients who were GBA variant carriers and have dysautonomia, and this association was enhanced if they have both.