Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, WC1N 3BG, London, UK.
Movement Disorders Unit, Neurology Service, Institut Clínic de Neurociències, Hospital Clínic de Barcelona, IDIBAPS, CIBERNED, 08036 Barcelona, Catalonia, Spain.
Brain. 2011 May;134(Pt 5):1493-1505. doi: 10.1093/brain/awr031.
The relative importance of Lewy- and Alzheimer-type pathologies to dementia in Parkinson's disease remains unclear. We have examined the combined associations of α-synuclein, tau and amyloid-β accumulation in 56 pathologically confirmed Parkinson's disease cases, 29 of whom had developed dementia. Cortical and subcortical amyloid-β scores were obtained, while tau and α-synuclein pathologies were rated according to the respective Braak stages. Additionally, cortical Lewy body and Lewy neurite scores were determined and Lewy body densities were generated using morphometry. Non-parametric statistics, together with regression models, receiver-operating characteristic curves and survival analyses were applied. Cortical and striatal amyloid-β scores, Braak tau stages, cortical Lewy body, Lewy neurite scores and Lewy body densities, but not Braak α-synuclein stages, were all significantly greater in the Parkinson's disease-dementia group (P<0.05), with all the pathologies showing a significant positive correlation to each other (P<0.05). A combination of pathologies [area under the receiver-operating characteristic curve=0.95 (0.88-1.00); P<0.0001] was a better predictor of dementia than the severity of any single pathology. Additionally, cortical amyloid-β scores (r=-0.62; P=0.043) and Braak tau stages (r=-0.52; P=0.028), but not Lewy body scores (r=-0.25; P=0.41) or Braak α-synuclein stages (r=-0.44; P=0.13), significantly correlated with mini-mental state examination scores in the subset of cases with this information available within the last year of life (n=15). High cortical amyloid-β score (P=0.017) along with an older age at onset (P=0.001) were associated with a shorter time-to-dementia period. A combination of Lewy- and Alzheimer-type pathologies is a robust pathological correlate of dementia in Parkinson's disease, with quantitative and semi-quantitative assessment of Lewy pathology being more informative than Braak α-synuclein stages. Cortical amyloid-β and age at disease onset seem to determine the rate to dementia.
路易体和阿尔茨海默病型病理改变对帕金森病痴呆的相对重要性仍不清楚。我们检查了 56 例经病理证实的帕金森病病例的 α-突触核蛋白、tau 和淀粉样β 积聚的联合关联，其中 29 例发生了痴呆。获得了皮质和皮质下淀粉样β 评分，同时根据各自的 Braak 阶段对 tau 和 α-突触核蛋白病理学进行评分。此外，还确定了皮质路易体和路易神经丝评分，并使用形态计量学生成了路易体密度。应用非参数统计学、回归模型、接收者操作特性曲线和生存分析。帕金森病痴呆组的皮质和纹状体淀粉样β评分、Braak tau 阶段、皮质路易体、路易神经丝评分和路易体密度均显著高于帕金森病非痴呆组（P<0.05），所有病理学均相互呈显著正相关（P<0.05）。与任何单一病理学相比，病理学的组合[接收者操作特性曲线下面积=0.95（0.88-1.00）；P<0.0001]是痴呆的更好预测指标。此外，皮质淀粉样β评分（r=-0.62；P=0.043）和 Braak tau 阶段（r=-0.52；P=0.028），而不是路易体评分（r=-0.25；P=0.41）或 Braak α-突触核蛋白阶段（r=-0.44；P=0.13），与生命最后一年中可用信息的病例的简易精神状态检查评分显著相关（n=15）。皮质高淀粉样β评分（P=0.017）和发病年龄较早（P=0.001）与痴呆时间较短有关。路易体和阿尔茨海默病型病理学的组合是帕金森病痴呆的强有力的病理相关性，定量和半定量评估路易体病理学比 Braak α-突触核蛋白阶段更具信息性。皮质淀粉样β和疾病发病年龄似乎决定了向痴呆的发展速度。
