神经学JO -神经学SP - e388 LP - e395 DO - 10.1212/WNL.0000000000201418半岛投注体育官网六世- 100 - 4 AU -林奥弗泰德尔博士盟乔迪- Maple-Grø民主党AU - Ingvild达伦AU - Ole-Bjørn Tysnes AU -科恩弗雷迪皮德森AU -吉多•阿尔维斯盟约翰内斯·兰格Y1 - 2023/01/24 UR - //www.ebmtp.com/content/100/4/e388.abstract N2 -背景和目标的变半岛投注体育官网化葡糖脑苷脂酶基因(GBA)是常见的帕金森病(PD)和痴呆的风险因素在PD (PDD)和导致溶酶体酶的活动减少葡糖脑苷脂酶(GCase)。虽然缺乏证据，但预计GCase功能障碍可能导致更恶性的病程，并预测PD的认知障碍。我们旨在发现新诊断的PD患者的CSF GCase活性是否发生改变，并与未来痴呆症的发展有关。方法PD患者是挪威西南部正在进行的基于人群的纵向ParkWest研究的参与者，并对其进行了长达10年的前瞻性随访。诊断时采集脑脊液，获取GBA载体状态。对照样本来自无神经退行性疾病的人。GCase活性用一种有效的测定方法测定。根据运动障碍协会(Movement Disorder Society)标准确定PD痴呆诊断，并应用参数加速失效时间模型分析GCase活动与无痴呆生存的关系。本研究纳入了117例PD患者(平均年龄67.2岁，包括12例GBA非同义变异携带者)和50例对照组(平均年龄64岁)。诊断时，与对照组(1.20±0.35,n = 50)相比，PD患者(平均±SD, 0.92±0.40 mU/mg, n = 12)或无GBA变化(1.00±0.37 mU/mg, n = 105)的GCase活性降低。 GCase activity at the time of diagnosis was lower in patients with PD who developed dementia within 10 years (0.85 ± 0.27 mU/mg, n = 41) than in those who did not (1.07 ± 0.40 mU/mg, n = 76, p = 0.001). A 0.1-unit reduction in baseline GCase activity was associated with a faster development of PDD (hazard ratio 1.15, 95% CI 1.03–1.28, p = 0.014).Discussion The association of early CSF GCase activity with long-term progression to PD dementia will have important implications for the design of clinical trials for GCase targeting therapies and patient management.Classification of Evidence This study provides Class III evidence that reduced CSF GCase activity at the time of PD diagnosis is associated with an increased risk for later development of PDD.CV%=coefficient of variation; GBA=glucocerebrosidase gene; GCase=glucocerebrosidase; HR=hazard ratio; IQR=interquartile range; LP=lumbar puncture; MMSE=Mini-Mental State Examination; PD=Parkinson disease; PDD=dementia in PD ER -