A clinico-pathological study of subtypes in Parkinson's disease
A clinico-pathological study of subtypes in Parkinson's disease
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DOI：
10.1093/brain/awp234
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发表时间：
2009-11-01
期刊：
影响因子：
14.5
通讯作者：
Lees, A. J.
中科院分区：
文献类型：
--
作者：
Selikhova, M.;Williams, D. R.;Lees, A. J.
我们对皇后广场神经疾病脑库的242例病理证实的帕金森病供体的病例档案进行了系统回顾，试图证实刘易斯及其同事提出的数据驱动亚型分类（使用数据驱动方法的早期临床阶段帕金森病的异质性）。J Neurol Neurosurg Psychiatry 2005; 76：343-8）。病例被分为早期疾病发作（25%），震颤显性（31%），非震颤显性（36%）和快速疾病进展无痴呆（8%）亚组。我们发现非震颤显性疾病模式和认知障碍之间存在很强的关联。发病较早组至死亡时间最长，福尔斯和认知功能下降发生时间最迟。震颤显性疾病模式患者的生存时间并不显著长于非震颤显性患者，并且在平均福尔斯和幻觉发作时间方面也没有差异。快速疾病进展与年龄较大、早期抑郁和早期中线运动症状相关，70%的病例出现震颤。非震颤显性亚组的皮质Lewy小体平均病理分级显著高于所有其他组（P < 0.05），皮质淀粉样β斑块负荷和脑淀粉样血管病显著高于早期疾病发作组和震颤显性组（P = 0.047）。对病理学定义的新皮质路易体病病例的分析证实了运动迟缓发作、认知能力下降和新皮质路易体沉积之间的联系。虽然神经病理学检查未能区分其他亚型，分类方案是由独立的基本亚组定义的临床数据分析支持。
We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.