Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Movement Disorders Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Spain; Center for Networked Biomedical Research in Neurodegenerative Diseases (CIBERNED, Carlos III Health Institute (ISCIII), Madrid, Spain.
Parkinsonism Relat Disord. 2024 Nov;128:107127. doi: 10.1016/j.parkreldis.2024.107127. Epub 2024 Sep 17.
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.
葡萄糖脑苷脂酶（GBA1）基因的杂合变体是帕金森病（PD）最常见的遗传风险因素。GBA1-PD 患者的疾病发病更早，运动功能受损更严重，认知能力下降更为明显。脑深部电刺激（DBS）为 PD 患者提供了运动改善，但它对认知的影响，特别是在 GBA1-PD 中，仍存在争议。
本研究纳入了 96 例于 2004 年至 2023 年期间在 Hospital de la Santa Creu i Sant Pau 接受丘脑底核 DBS 的 PD 患者。在手术前后进行了临床和神经心理学评估，重点评估了 Mattis 痴呆评定量表（MDRS）和额叶系统行为量表（FrSBe）。患者分为 GBA1-PD 和非 GBA1-PD 组，非 GBA1-PD 进一步分为认知快速进展者和缓慢进展者。
13.5%的患者存在 GBA1 变异。与非 GBA1-PD 患者相比，GBA1-PD 患者随时间推移认知能力下降更为明显，尤其是在注意力、概念化和记忆力方面。非 GBA1-PD 快速进展者在 DBS 后第一年的启动和概念化方面表现出显著的认知恶化。所有组的运动结果改善相似，但缓慢进展者的左旋多巴等效日剂量（LEDD）降低幅度更大。
GBA1-PD 患者经历更快的认知衰退，特别是在后皮质和额纹状体功能方面。此外，一部分非 GBA1-PD 患者在 DBS 后出现显著的早期认知衰退，尤其是在执行功能方面。基线 MDRS 评分不能预测认知结果，这突出表明需要进一步研究以完善预后工具。尽管存在认知挑战，但 GBA1-PD 患者在运动结果方面受益于 DBS，这凸显了无论遗传状况如何，对 DBS 适用性进行个体化评估的重要性。
