Cambridge Centre for Brain Repair, University of Cambridge, UK.
J Parkinsons Dis. 2011;1(1):75-82. doi: 10.3233/JPD-2011-0002.
The optimum method for evaluating disease progression in Parkinson's disease (PD) has not been established, and this has implications for clinical trials. The majority of previous studies have utilized change on the Unified Parkinson's disease Rating Scale (UPDRS) as an index of progression. However, the UPDRS has not been validated for this purpose. We utilized exploratory factor analysis (EFA) to evaluate the longitudinal properties of the UPDRS as an index of disease progression in PD. Data was derived from a representative cohort of 122 PD patients followed from diagnosis and assessed every 18-24 months for up to 7.9 years. For each subject the rate of change of each item on the UPDRS-3 was calculated and an EFA was performed using this data. Results were compared with those of previously published EFAs in cross-sectional PD cohorts. The UPDRS-3 retains a stable factor structure when used as an index of disease evolution. The 27 items reduced to 6 factors which accounted for 61.0% of the variance in disease progression. A dominant factor was identified which incorporated axial (gait/postural stability) symptoms and signs. Our analysis indicates that the UPDRS captures meaningful aspects of disease progression in PD, and that it is possible to identify symptom/sign complexes which evolve independently of one another. Progression in PD is predominantly characterized by the development of axial symptoms and signs. This result has implications for pathogenesis and should also inform natural history models of PD thereby allowing identification of meaningful outcome measures for clinical trials of disease-modifying therapies.
尚未确定评估帕金森病 (PD) 疾病进展的最佳方法,这对临床试验有影响。之前的大多数研究都使用统一帕金森病评定量表 (UPDRS) 的变化作为疾病进展的指标。然而,UPDRS 尚未对此目的进行验证。我们利用探索性因子分析 (EFA) 来评估 UPDRS 作为 PD 疾病进展指标的纵向特性。数据来自一个代表性的 PD 患者队列,从诊断开始随访,每 18-24 个月评估一次,最长可达 7.9 年。对于每个患者,计算 UPDRS-3 中每个项目的变化率,并使用该数据进行 EFA。结果与以前在横断面 PD 队列中发表的 EFA 进行了比较。当用作疾病演变的指标时,UPDRS-3 保留了稳定的因子结构。27 项减少到 6 个因子,占疾病进展变异的 61.0%。确定了一个主导因子,其中包含了轴性(步态/姿势稳定性)症状和体征。我们的分析表明,UPDRS 捕捉到了 PD 疾病进展的有意义方面,并且可以识别彼此独立演变的症状/体征复合物。PD 的进展主要表现为轴性症状和体征的发展。这一结果对发病机制有影响,也应该为 PD 的自然史模型提供信息,从而为疾病修饰疗法的临床试验确定有意义的结局指标。