Department of Neurology, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
Department of Statistics, Rutgers University, Piscataway, New Jersey, USA.
Ann Clin Transl Neurol. 2024 Apr;11(4):899-904. doi: 10.1002/acn3.52005. Epub 2024 Feb 9.
Mutations in the glucocerebrosidase (GBA1) gene and subthalamic nucleus deep brain stimulation (STN-DBS) are independently associated with cognitive dysfunction in persons with Parkinson's disease (PwP). We hypothesized that PwP with both GBA1 mutations and STN-DBS are at greater risk of cognitive dysfunction than PwP with only GBA1 mutations or STN-DBS, or neither. In this study, we determined the pattern of cognitive dysfunction in PwP based on GBA1 mutation status and STN-DBS treatment.
PwP who are GBA1 mutation carriers with or without DBS (GBA1+DBS+, GBA1+DBS-), and noncarriers with or without DBS (GBA1-DBS+, GBA1-DBS-) were included. Using the NIH Toolbox, cross-sectional differences in response inhibition, processing speed, and episodic memory were compared using analysis of variance with adjustment for relevant covariates.
Data were available for 9 GBA1+DBS+, 14 GBA1+DBS-, 17 GBA1-DBS+, and 26 GBA1-DBS- PwP. In this cross-sectional study, after adjusting for covariates, we found that performance on the Flanker test (measure of response inhibition) was lower in GBA1+DBS+ PwP compared with GBA1-DBS+ PwP (P = 0.030).
PwP who carry GBA1 mutations and have STN-DBS have greater impaired response inhibition compared with PwP with STN-DBS but without GBA1 mutations. Longitudinal data, including preoperative scores, are required to definitively determine whether GBA1 mutation carriers respond differently to STN-DBS, particularly in the domain of response inhibition.
葡萄糖脑苷脂酶（GBA1）基因突变和丘脑底核深部脑刺激（STN-DBS）与帕金森病患者（PwP）的认知功能障碍独立相关。我们假设同时携带 GBA1 基因突变和 STN-DBS 的 PwP 比仅携带 GBA1 基因突变或 STN-DBS 或两者都不携带的 PwP 发生认知功能障碍的风险更高。在这项研究中，我们根据 GBA1 基因突变状态和 STN-DBS 治疗确定了 PwP 的认知功能障碍模式。
纳入携带或不携带 GBA1 基因突变且行或不行 DBS（GBA1+DBS+、GBA1+DBS-）的 PwP，以及携带或不携带 GBA1 基因突变且行或不行 DBS（GBA1-DBS+、GBA1-DBS-）的 PwP。使用 NIH 工具包，通过方差分析比较不同组别间反应抑制、处理速度和情景记忆的差异，并对相关协变量进行调整。
9 名 GBA1+DBS+、14 名 GBA1+DBS-、17 名 GBA1-DBS+和 26 名 GBA1-DBS- PwP 的数据可用。在这项横断面研究中，调整协变量后，我们发现与 GBA1-DBS+ PwP 相比，GBA1+DBS+ PwP 的 Flanker 测试（反应抑制测量）得分较低（P=0.030）。
与仅携带 STN-DBS 但无 GBA1 基因突变的 PwP 相比，携带 GBA1 基因突变且行 STN-DBS 的 PwP 的反应抑制受损更严重。需要纵向数据，包括术前评分，才能明确确定 GBA1 基因突变携带者对 STN-DBS 的反应是否不同，特别是在反应抑制方面。
