Disease progression in Parkinson subtypes: the PPMI dataset
Disease progression in Parkinson subtypes: the PPMI dataset
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DOI：
10.1007/s10072-018-3522-z
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发表时间：
2018-11-01
影响因子：
3.3
通讯作者：
Antonini, Angelo
中科院分区：
文献类型：
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作者：
Aleksovski, Darko;Miljkovic, Dragana;Antonini, Angelo
帕金森病患者出现显性震颤（TD）或姿势不稳定性步态障碍（PIGD）时，病情进展呈离散模式。然而，纵向前瞻性评估需要考虑到临床表现的变异性和证据表明，只有40%的最初分类PIGD保持在这种亚型在随后visits.MethodsWe分析了PIGD的临床进展相比，TD使用纵向临床数据从PPMI。考虑到报告的此类临床分类的不稳定性，我们仅纳入了4年观察期间每次访视时报告为PIGD/TD的患者。我们使用线性混合效应模型来测试这些亚组在51个因变量中的进展差异。PIGD的数量为36/254 vs 144/254 TD。PIGD在基线时有更严重的运动疾病，但仅在MDS-MRS的三个非运动项目中进展快于TD：认知障碍、幻觉和精神病加上DDS特征。我们的分析还表明，在PIGD更快的平均时间增加与dyskinesia.ConclusionsPIGD的特点是更严重的疾病表现在诊断和更大的认知进展，更频繁的幻觉，精神病以及功能的DDS比TD患者。我们将这些发现解释为PIGD在发病时已经表现出更大的皮质和皮质下受累。由于PIGD/TD分类在发病时非常不稳定，我们基于更严格的定义标准进行的分析为临床试验分层和相关结局指标的定义提供了重要的见解。
IntroductionDiscrete patterns of progression have been suggested for patients with Parkinson disease and presenting tremor dominant (TD) or postural instability gait disorders (PIGD). However, longitudinal prospective assessments need to take into consideration the variability in clinical manifestations and the evidence that only 40% of initially classified PIGD remain in this subtype at subsequent visits.MethodsWe analyzed clinical progression of PIGD compared to TD using longitudinal clinical data from the PPMI. Given the reported instability of such clinical classification, we only included patients who were reported as PIGD/TD at each visit during the 4-year observation. We used linear mixed-effects models to test differences in progression in these subgroups in 51 dependent variables.ResultsThere were 254 patients with yearly assessment. The number of PIGD was 36/254 vs 144/254 TD. PIGD had more severe motor disease at baseline but progressed faster than TD only in three non-motor items of the MDS-UPDRS: cognitive impairment, hallucinations, and psychosis plus features of DDS. Our analysis also showed in PIGD faster increase in the average time with dyskinesia.ConclusionsPIGD are characterized by more severe disease manifestations at diagnosis and greater cognitive progression, more frequent hallucinations, psychosis as well as features of DDS than TD patients. We interpret these findings as expression of greater cortical and subcortical involvement in PIGD already at onset. Since PIGD/TD classification is very unstable at onset, our analysis based on stricter definition criteria provides important insight for clinical trial stratification and definition of related outcome measures.