Are there morphological differences between Parkinson's disease-dementia and dementia with Lewy bodies?
Are there morphological differences between Parkinson's disease-dementia and dementia with Lewy bodies?
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DOI：
10.1016/j.parkreldis.2022.05.024
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发表时间：
2022-06-09
影响因子：
4.1
通讯作者：
Jellinger, Kurt A.
中科院分区：
文献类型：
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作者：
Jellinger, Kurt A.
帕金森病痴呆（PDD）和路易体痴呆（DLB）是路易体病谱系中的两种主要神经认知障碍，尽管它们显示出若干差异，但在许多临床和神经病理学特征上重叠。临床上主要根据帕金森综合征在痴呆发展之前的持续时间来区分，其形态学特征是路易体（LB）和阿尔茨海默病（AD）病理学的可变组合，后者通常在DLB中更频繁和严重。目的：本研究的目的是在更大的尸检病例队列中研究PDD和DLB之间的基本神经病理学差异。110例PDD尸检与78例DLB尸检进行比较。主要的人口统计学，临床（病程，最终MMSE）和神经病理学数据进行了回顾性评估。神经病理学研究采用标准化的方法和磷酸化tau蛋白，β-淀粉样蛋白（A β）和α-突触核蛋白的免疫组化，与半定量评估的主要组织学lesions.Results：PDD患者的死亡年龄显着大于DLB的（平均83.9与79.8年），与一个显着较长的疾病持续时间（平均9.2与6.7年）。DLB组的Braak LB评分和尤其是神经炎性Braak分期显著较高（分别为平均5.1和5.1 vs. 4.2和4.4），塔尔A β期也是如此（平均4.1 vs. 3.0）。弥漫性纹状体A β斑块在55%的DLB病例中相当可观，在45%的DLB病例中为中度，但在PDD中极为罕见。最显著的差异涉及脑淀粉样血管病（CAA）的频率和程度，DLB显著更高（分别为98.7%和50%，平均程度分别为2.9%和0.72）。DLB比PDD预后差与Braak神经炎阶段增加和更严重的CAA.Interpretation：这些和其他最近的研究意味着CAA，更严重的伴随AD病理，和纹状体A β负荷与认知能力下降和更快速的疾病过程，区分DLB从PDD的关联，而其他脑血管疾病或共同病理在这两种疾病的影响没有特别检查。CAA和tau病理学在DLB中的重要性以及在PDD中的重要性少得多，这支持了帕金森病（PD）- > PDD - > DLB - > DLB + AD和具有年龄相关蛋白病谱内的LB病理学的AD亚型的发病连续体的概念。
Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are two major neurocognitive disorders in the spectrum of Lewy body diseases that overlap in many clinical and neuropathological features, although they show several differences. Clinically distinguished mainly based on the duration of parkinsonism prior to development of dementia, their morphology is characterized by a variable combination of Lewy body (LB) and Alzheimer's disease (AD) pathologies, the latter usually being more frequent and severe in DLB.Objective: The aims of the study were to investigate essential neuropathological differences between PDD and DLB in a larger cohort of autopsy cases.Methods: 110 PDD autopsy cases were compared with 78 DLB cases. The major demographic, clinical (duration of illness, final MMSE) and neuropathological data were assessed retrospectively. Neuropathological studies used standardized methods and immunohistochemistry for phospho-tau, beta-amyloid (A beta) and a-synuclein, with semiquantitative assessment of the major histological lesions.Results: PDD patients were significantly older at death than DLB ones (mean 83.9 vs. 79.8 years), with a significantly longer disease duration (mean 9.2 vs. 6.7 years). Braak LB scores and particularly neuritic Braak stages were significantly higher in the DLB group (mean 5.1and 5.1 vs. 4.2 and 4.4, respectively), as were Thal A beta phases (mean 4.1 vs. 3.0). Diffuse striatal A beta plaques were considerable in 55% and moderate in 45% of DLB cases, but were extremely rare in PDD. The most significant differences concerned the frequency and degree of cerebral amyloid angiopathy (CAA), being significantly higher in DLB (98.7 vs. 50%, and mean degree of 2.9 vs. 0.72, respectively). Worse prognosis in DLB than in PDD was linked to both increased Braak neuritic stages and more severe CAA.Interpretation: These and other recent studies imply the association of CAA, more severe concomitant AD pathology, and striatal A beta load with cognitive decline and more rapid disease process that distinguishes DLB from PDD, while the influence of other cerebrovascular diseases or co-pathologies in both disorders was not specifically examined. The importance of both CAA and tau pathology in DLB and much less in PDD supports the concept of a pathogenetic continuum from Parkinson's disease (PD) - > PDD - > DLB - > DLB + AD and subtypes of AD with LB pathology within the spectrum of age-related proteinopathies.