Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois.
Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois.
J Gerontol A Biol Sci Med Sci. 2021 Mar 31;76(4):615-621. doi: 10.1093/gerona/glaa176.
Mixed-brain pathologies are the most common cause of progressive parkinsonism in older adults. We tested the hypothesis that the impact of individual pathologies associated with progressive parkinsonism differs among older adults.
Data were from 1089 decedents who had undergone annual clinical testing and autopsy. Parkinsonism was based on a modified United Parkinson's Disease Rating Scale. Linear mixed-effects models were employed, to investigate the combinations of 9 pathologies related to progressive parkinsonism. Then we estimated the person-specific contributions of each pathology for progressive parkinsonism.
The average participant showed 3 pathologies. Parkinson's disease (PD) and 4 cerebrovascular pathologies (macroinfarcts, atherosclerosis, arteriolosclerosis, and cerebral amyloid angiopathy [CAA]), but not Alzheimer's disease, TDP-43, hippocampal sclerosis, and microinfarcts, were independently associated with progressive parkinsonism. These pathologies accounted for 13% of additional variance of progressive parkinsonism. Thirty-one different combinations of these 5 pathologies were observed to be associated with progressive parkinsonism observed. On average, PD and CAA accounted, respectively, for 66% and 65% of person-specific progression of parkinsonism, while macroinfarcts, atherosclerosis, and arteriolosclerosis accounted for 41%-48%.
There is much greater heterogeneity in the comorbidity and relative impact of individual brain pathologies affecting progressive parkinsonism than previously recognized and this may account in part for its phenotypic heterogeneity in older adults.
混合性脑病理学是导致老年人进行性帕金森病的最常见原因。我们检验了以下假说，即与进行性帕金森病相关的个体病理学的影响在老年人中存在差异。
数据来自 1089 名已故者，他们接受了年度临床测试和尸检。帕金森病是基于改良的帕金森病评定量表。采用线性混合效应模型，研究了 9 种与进行性帕金森病相关的病理学的组合。然后，我们估计了每种病理学对进行性帕金森病的个体贡献。
平均每位参与者有 3 种病理学。帕金森病（PD）和 4 种脑血管病理学（大梗死、动脉粥样硬化、小动脉硬化和脑淀粉样血管病[CAA]），但不是阿尔茨海默病、TDP-43、海马硬化和微梗死，与进行性帕金森病独立相关。这些病理学解释了进行性帕金森病额外变异的 13%。观察到这 5 种病理学的 31 种不同组合与进行性帕金森病相关。平均而言，PD 和 CAA 分别占帕金森病进展的 66%和 65%，而大梗死、动脉粥样硬化和小动脉硬化占 41%-48%。
与进行性帕金森病相关的脑病理学的合并症和个体影响存在更大的异质性，这在一定程度上可以解释老年人其表型的异质性。
