脑脊液葡萄糖脑苷酶活性与帕金森病患者痴呆发生风险的关系[j] - Neurology - 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)。尽管缺乏证据，但预计GCase功能障碍可能有助于PD的恶性病程，并预测PD的认知障碍。我们的目的是发现脑脊液GCase活性是否在新诊断的PD患者中发生改变，并与痴呆的未来发展相关。方法PD患者是挪威西南部正在进行的以人群为基础的ParkWest纵向研究的参与者，前瞻性随访长达10年。诊断时采集脑脊液，获得GBA携带者状态。对照样本来自无神经退行性疾病的人。GCase活性测定采用验证法。根据运动障碍学会标准设定PD痴呆诊断，并应用参数加速失效时间模型分析GCase活性与无痴呆生存的关系。结果本研究纳入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名对照参与者(平均年龄64岁)。诊断时，PD患者GCase活性(平均±SD, 0.92±0.40 mU/mg, n = 12)或无GBA变化(1.00±0.37 mU/mg, n = 105)低于对照组(1.20±0.35,n = 50)。 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 -