Clinical and Biological Determinants of Longitudinal Cognitive Function in Patients With GBA1 Variants and Subthalamic Deep Brain Stimulation

OBJECTIVE: Whether cognitive decline in patients with Parkinson's disease (PD) carrying GBA1 variants is accelerated after subthalamic deep brain stimulation (STN-DBS) remains controversial. Clarifying long-term cognitive outcomes is essential for informed decision making. METHODS: , n = 43). Clinical, genetic, and cerebrospinal fluid (CSF) biomarkers (Aβ1-42, h-Tau, p181-Tau, and neurofilament light chain) were analyzed. Cognition was assessed using the Montreal Cognitive Assessment (MoCA). Cognitive slopes were estimated using linear mixed models and the minimally detectable slope difference at 3-year follow-up was 1.33 MoCA points enabling sensitivity to clinically meaningful changes. Secondarily, conversion to dementia was analyzed with Kaplan-Meier-analysis once the MoCA was < 21. RESULTS: (HR = 1.22, 95% CI = 0.53-2.83, p = 0.897). Dementia risk was associated with GBA1 status (HR = 3.04, 95% CI = 1.05-8.79, p = 0.041), baseline MoCA < 26 (HR = 3.05, 95% CI = 1.29-7.21, p = 0.011), and baseline age > 69 years (HR = 4.42, 95% CI = 1.79-10.89, p = 0.001). In GBA1 carriers, a visuospatial/executive domain score < 4/5 predicted dementia (HR = 4.71, 95% CI = 1.25-17.86, p = 0.022). INTERPRETATION: GBA1 variant carriers meeting general STN-DBS indication criteria did not show accelerated cognitive decline in the presence of STN-DBS. In addition, exploratory predictors of dementia could support counseling of DBS candidates. ANN NEUROL 2026;99:976-988.