Reimer J, Schumann F, Gruber D, Schneider GH, Krause T, Kühn AA, Krause P.

Parkinsonism Relat Disord. 2026 May 23; 148: 108355. doi: 10.1016/j.parkreldis.2026.108355. Epub ahead of print. PMID: 42214115.

Abstract

Background: Patients with Parkinson’s disease (PD) who carry Glucocerebrosidase 1 (GBA) mutations (GBA + PD) demonstrate a more aggressive motor and non-motor disease course. While subthalamic nucleus deep brain stimulation (STN-DBS) is effective for advanced PD, its cognitive impact in GBA + PD patients remains controversial, and individual predictors of DBS outcome are lacking.

Methods: We applied region-based morphometry (RBM) using the CAT12-toolbox to identify baseline atrophy patterns in GBA + PD patients undergoing evaluation for STN-DBS. Region of interest (ROI) volumes were retrieved from the Jülich Brain Atlas (Version 3.1). Modulation of Mini-Mental-State Examination (MMSE) and Unified Parkinson’s Disease Rating Scale motor part (UPDRS-III) trajectories by ROI-volumes and moderation by mutation status were assessed using linear mixed-effect models.

Results: At baseline, 20 GBA + PD patients exhibited significantly reduced volumes of the right fusiform gyrus subunit 5 compared to 30 patients without GBA mutation (GBA-PD) (p = 0.0018, Holm-Bonferroni-corrected). Uncorrected results include atrophy of the left nucleus basalis of Meynert (NBM) (p = 0.017), medial temporal lobe volumes and greater volume of the left frontal operculum subunits 8 and 9 (FOp9 p = 0.009; FOp8 p = 0.014) in GBA + PD. No significant MMSE decline did occur in 18 GBA + PD patients one year after STN-DBS. Both groups showed significant improvement on UPDRS-III. Contradictory, higher left NBM volume led to a trend (p = 0.037, uncorrected) of greater MMSE decline, which did not persist when FOp9 volume was added to the model as a covariate.

Conclusion: We therefore hypothesized; increased FOp volumes might be a structural correlate of the cognitive reserve.