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] [j] [j] [j] [j] [j] [j]半岛投注体育官网背景与目的糖脑苷酶基因(GBA)的变异是帕金森病(PD)和帕金森病痴呆(PDD)的常见危险因素，并导致溶酶体酶-葡萄糖脑苷酶(GCase)活性降低。半岛投注体育官网尽管缺乏证据，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

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