Cognitive phenotyping of GBA1-Parkinson's disease: A study on deep brain stimulation outcomes

• Published in: Parkinsonism & related disorders 2024-11, Vol.128, p.107127, Article 107127
• Main Authors: Fernández-Vidal, Joan Miquel, Aracil-Bolaños, Ignacio, García-Sánchez, Carmen, Campolongo, Antonia, Curell, Mireia, Rodríguez-Rodriguez, Rodrigo, Aibar-Duran, Juan Ángel, Kulisevsky, Jaime, Pascual-Sedano, Berta
• Format: Article
• Language: English
• Subjects: Aged; Cognition; Cognitive Dysfunction - etiology; Cognitive Dysfunction - physiopathology; Cognitive Dysfunction - therapy; Cognitive phenotype; Deep Brain Stimulation; Disease Progression; Female; GBA1; Genetics; Glucosylceramidase - genetics; Humans; Male; Middle Aged; Parkinson Disease - complications; Parkinson Disease - genetics; Parkinson Disease - therapy; Parkinson's disease; Phenotype; Subthalamic Nucleus; Treatment Outcome
• ISSN: 1353-8020; 1873-5126; 1873-5126
• DOI: 10.1016/j.parkreldis.2024.107127

Heterozygous variants in the glucocerebrosidase (GBA1) gene are the most common genetic risk factor for Parkinson's Disease (PD). GBA1-PD patients exhibit earlier disease onset, severe motor impairment, and heightened cognitive decline. Deep Brain Stimulation (DBS) offers motor improvement for PD patients, but its cognitive effects, particularly in GBA1-PD, are debated. This study involved 96 PD patients who underwent subthalamic nucleus DBS at Hospital de la Santa Creu i Sant Pau between 2004 and 2023. Clinical and neuropsychological assessments were conducted pre- and post-surgery, focusing on Mattis Dementia Rating Scale (MDRS) and Frontal Systems Behavior Scale (FrSBe). Patients were categorized into GBA1-PD and non-GBA1-PD groups, with non-GBA1-PD further divided into cognitive fast-progressors and slow-progressors. GBA1 variants were present in 13.5 % of patients. GBA1-PD patients showed greater cognitive decline over time, particularly in attention, conceptualization, and memory, compared to non-GBA1-PD. Non-GBA1-PD fast-progressors exhibited significant cognitive deterioration in initiation and conceptualization within the first year post-DBS. Motor outcomes improved similarly across all groups, but slow-progressors showed a greater reduction in Levodopa Equivalent Daily Dose (LEDD). GBA1-PD patients experience more rapid cognitive decline, particularly in posterior-cortical and fronto-striatal functions. Additionally, a subset of non-GBA1-PD patients shows significant early cognitive decline post-DBS, especially in executive functions. Baseline MDRS scores do not predict cognitive outcomes, highlighting the need for further research to refine prognostic tools. Despite cognitive challenges, GBA1-PD patients benefit from DBS in terms of motor outcomes, underscoring the importance of individualized assessments for DBS suitability, regardless of genetic status. •GBA1-PD patients benefit from DBS motor improvements; genetic factors should not preclude DBS.•GBA1-PD decline marked by initial posterior-cortical and later fronto-striatal dysfunction.•Baseline MDRS scores don't predict cognitive trajectory