Department of Neurology, 330 South 9th Street, Second Floor, Philadelphia, PA 19107, USA.
Neurology. 2010 Sep 21;75(12):1055-61. doi: 10.1212/WNL.0b013e3181f39a78. Epub 2010 Aug 18.
Cognitive decline associated with Parkinson disease (PD) is common and highly disabling. Biomarkers that help identify patients at risk for cognitive decline would be useful additions to the clinical management of the disease.
A total of 45 patients with PD were enrolled in this prospective cohort study and had at least 1 yearly longitudinal follow-up evaluation. CSF was collected at baseline and cognition was assessed at baseline and follow-up visits using the Mattis Dementia Rating Scale (DRS-2). CSF was tested for amyloid β 1-42 (Aβ(1-42)), p-tau(181p), and total tau levels using the Luminex xMAP platform. Mixed linear models were used to test for associations between baseline CSF biomarker levels and change in cognition over time.
Lower baseline CSF Aβ(1-42) was associated with more rapid cognitive decline. Subjects with CSF Aβ(1-42) levels ≤192 pg/mL declined an average of 5.85 (95% confidence interval 2.11-9.58, p = 0.002) points per year more rapidly on the DRS-2 than subjects above that cutoff, after adjustment for age, disease duration, and baseline cognitive status. CSF total tau and p-tau(181p) levels were not significantly associated with cognitive decline.
Reduced CSF Aβ(1-42) was an independent predictor of cognitive decline in patients with PD. This observation is consistent with previous research showing that Alzheimer disease pathology contributes to cognitive impairment in PD. This biomarker may provide clinically useful prognostic information, particularly if combined with other risk factors for cognitive impairment in PD.
与帕金森病(PD)相关的认知能力下降很常见且严重致残。有助于识别认知能力下降风险患者的生物标志物将有助于该病的临床管理。
这项前瞻性队列研究共纳入了 45 名 PD 患者,他们至少接受了 1 年的纵向随访评估。在基线时采集 CSF,并使用 Mattis 痴呆评定量表(DRS-2)在基线和随访时评估认知功能。使用 Luminex xMAP 平台检测 CSF 中的淀粉样蛋白β 1-42(Aβ(1-42))、p- tau(181p)和总 tau 水平。采用混合线性模型检验基线 CSF 生物标志物水平与随时间变化的认知变化之间的相关性。
较低的基线 CSF Aβ(1-42)与认知下降速度较快有关。CSF Aβ(1-42)水平≤192 pg/mL 的患者在 DRS-2 上的年平均下降幅度比该截点以上的患者快 5.85 分(95%置信区间 2.11-9.58,p = 0.002),调整年龄、疾病持续时间和基线认知状态后仍有显著差异。CSF 总 tau 和 p- tau(181p)水平与认知下降无显著相关性。
CSF Aβ(1-42)减少是 PD 患者认知下降的独立预测因素。这一观察结果与先前的研究一致,表明阿尔茨海默病病理学导致 PD 患者认知障碍。该生物标志物可能提供有用的临床预后信息,特别是如果与 PD 认知障碍的其他风险因素相结合。