From the Rush Alzheimer's Disease Center (A.S.B., L.Y., R.S.W., S.E.L., S.N., L.L.B., J.A.S., D.A.B.), and Departments of Neurological Sciences (A.S.B., L.Y., R.S.W., S.E.L., J.A.S., D.A.B.), Behavioral Sciences (R.S.W., L.L.B.), and Pathology (Neuropathology) (S.N., J.A.S.), Rush University Medical Center, Chicago, IL; Departments of Neurology, Molecular and Human Genetics, Neuroscience, and Program in Developmental Biology (J.M.S.), Baylor College of Medicine, Houston, TX; and Jan and Dan Duncan Neurological Research Institute (J.M.S.), Texas Children's Hospital, Houston.
Neurology. 2019 Apr 16;92(16):e1821-e1830. doi: 10.1212/WNL.0000000000007315. Epub 2019 Mar 20.
To examine whether indices of Parkinson disease (PD) pathology and other brain pathologies are associated with the progression of parkinsonism in older adults.
We used data from decedents who had undergone annual clinical testing prior to death and structured brain autopsy. Parkinsonism was based on assessment with a modified Unified Parkinson's Disease Rating Scale and a clinical diagnosis of PD was based on medical history. We used a series of mixed-effects models controlling for age and sex to investigate the association of PD pathology (nigral neuronal loss and Lewy bodies) and indices of 8 other brain pathologies with the progression of parkinsonism prior to death.
During an average of 8.5 years' follow-up, more than half (771/1,430, 53.9%) developed parkinsonism proximate to death. On average, parkinsonism was progressive (estimate 0.130, SE 0.005, < 0.001) in all older adults, but more rapid in adults with a clinical diagnosis of PD (n = 52; 3.6%) (estimate 0.066, SE 0.021, < 0.001). Progression of parkinsonism was more rapid in adults with PD pathology (estimate 0.087, SE 0.013, < 0.001). Alzheimer disease and several cerebrovascular pathologies were all independently associated with more rapid progression (all values <0.05). The association between a higher person-specific weighted pathology score and more rapidly progressive parkinsonism did not differ between individuals with and without a clinical diagnosis of PD (estimate 0.003, SE 0.047, = 0.957).
The rate of progressive parkinsonism in older adults with and without a clinical diagnosis of PD is related to the burden of mixed brain pathologies.
探讨帕金森病（PD）病理学和其他脑病理学指标是否与老年人帕金森病进展有关。
我们使用了在死亡前进行了年度临床检查和结构化脑尸检的死者数据。帕金森病是基于改良的统一帕金森病评定量表（Unified Parkinson's Disease Rating Scale）评估和基于病史的 PD 临床诊断。我们使用一系列混合效应模型，控制年龄和性别，来研究 PD 病理学（黑质神经元丧失和路易体）和其他 8 种脑病理学指标与死亡前帕金森病进展的关系。
在平均 8.5 年的随访中，超过一半（771/1430，53.9%）的人在接近死亡时出现帕金森病。平均而言，所有老年人的帕金森病都是进行性的（估计值 0.130，SE 0.005，<0.001），但具有 PD 临床诊断的成年人更快（n=52；3.6%）（估计值 0.066，SE 0.021，<0.001）。PD 病理学患者的帕金森病进展更快（估计值 0.087，SE 0.013，<0.001）。阿尔茨海默病和几种脑血管病理学均与更快的进展独立相关（所有 P 值均<0.05）。具有和不具有 PD 临床诊断的个体之间，更高的个体加权病理学评分与更快进展的帕金森病之间的关联没有差异（估计值 0.003，SE 0.047，P=0.957）。
有和没有 PD 临床诊断的老年人进行性帕金森病的发生率与混合性脑病理学负担有关。
