Motor and Cognitive Outcome After Subthalamic Nucleus Deep Brain Stimulation in Patients with Parkinson's Disease...

Deep brain stimulation (DBS) is effective for Parkinson's disease (PD); however, its efficacy varies with genetic background, such as the GBA1 variant-the causative gene of Gaucher disease-associated with increased PD risk and cognitive decline after subthalamic nucleus (STN)-DBS.

The aim of the study was to examine the relationship between outcomes after STN-DBS and GBA1 variants in PD patients undergoing bilateral STN-DBS.

Patients were retrospectively analyzed over 5 years, with clinical and genetic assessments, including GBA1 variant status performed at baseline and at 1-, 3-, and 5-years post-DBS. Longitudinal changes in motor, cognitive, and medication outcomes were evaluated using propensity score matching and linear mixed-effects models.

A total of 371 PD patients undergoing bilateral STN-DBS were analyzed, including 54 GBA1 variant carriers and 253 noncarriers, after excluding other genetic variants. Propensity score matching yielded 2 groups with balanced baseline characteristics, with 50 patients each. Over time, no significant differences were observed in motor, cognitive, or neuropsychiatric assessments between groups. GBA1 carriers exhibited worsened medication OFF-DBS off state motor symptoms at 5 years postoperatively, whereas cognitive function, assessed by the Mini-Mental State Examination, remained stable in both groups. Levodopa-equivalent daily dose (LEDD) significantly decreased in both groups. Linear mixed-effects models showed progressive motor and cognitive decline and reduced medication use over 5 years, with no significant impact on GBA1 variant status.

Findings from Japan's largest genetic cohort suggest that GBA1 variants may not significantly affect postoperative motor or cognitive trajectories following STN-DBS. Further validation through large-scale multinational and multicenter studies is warranted.