Institute for Health Metrics and Evaluation, University of Washington, Seattle, WA, USA.
Cambridge Public Health, University of Cambridge, Cambridge, UK.
Lancet Healthy Longev. 2023 Mar;4(3):e115-e125. doi: 10.1016/S2666-7568(23)00019-3.
Population-based autopsy studies provide valuable insights into the causes of dementia but are limited by sample size and restriction to specific populations. Harmonisation across studies increases statistical power and allows meaningful comparisons between studies. We aimed to harmonise neuropathology measures across studies and assess the prevalence, correlation, and co-occurrence of neuropathologies in the ageing population.
We combined data from six community-based autopsy cohorts in the US and the UK in a coordinated cross-sectional analysis. Among all decedents aged 80 years or older, we assessed 12 neuropathologies known to be associated with dementia: arteriolosclerosis, atherosclerosis, macroinfarcts, microinfarcts, lacunes, cerebral amyloid angiopathy, Braak neurofibrillary tangle stage, Consortium to Establish a Registry for Alzheimer's disease (CERAD) diffuse plaque score, CERAD neuritic plaque score, hippocampal sclerosis, limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC), and Lewy body pathology. We divided measures into three groups describing level of confidence (low, moderate, and high) in harmonisation. We described the prevalence, correlations, and co-occurrence of neuropathologies.
The cohorts included 4354 decedents aged 80 years or older with autopsy data. All cohorts included more women than men, with the exception of one study that only included men, and all cohorts included decedents at older ages (range of mean age at death across cohorts 88·0-91·6 years). Measures of Alzheimer's disease neuropathological change, Braak stage and CERAD scores, were in the high confidence category, whereas measures of vascular neuropathologies were in the low (arterioloscerosis, atherosclerosis, cerebral amyloid angiopathy, and lacunes) or moderate (macroinfarcts and microinfarcts) categories. Neuropathology prevalence and co-occurrence was high (2443 [91%] of 2695 participants had more than one of six key neuropathologies and 1106 [41%] of 2695 had three or more). Co-occurrence was strongly but not deterministically associated with dementia status. Vascular and Alzheimer's disease features clustered separately in correlation analyses, and LATE-NC had moderate associations with Alzheimer's disease measures (eg, Braak stage ρ=0·31 [95% CI 0·20-0·42]).
Higher variability and more inconsistency in the measurement of vascular neuropathologies compared with the measurement of Alzheimer's disease neuropathological change suggests the development of new frameworks for the measurement of vascular neuropathologies might be helpful. Results highlight the complexity and multi-morbidity of the brain pathologies that underlie dementia in older adults and suggest that prevention efforts and treatments should be multifaceted.
Gates Ventures.
基于人群的尸检研究为痴呆症的病因提供了有价值的见解，但受到样本量和特定人群限制的限制。研究之间的协调一致可以提高统计效力，并允许在研究之间进行有意义的比较。我们旨在协调跨研究的神经病理学测量，并评估老年人群中神经病理学的患病率、相关性和共同发生。
我们在美国和英国的六个基于社区的尸检队列中合并了数据，进行了一项协调的横断面分析。在所有 80 岁或以上的死者中，我们评估了 12 种已知与痴呆症相关的神经病理学：小动脉硬化、动脉粥样硬化、大梗塞、微梗塞、腔隙、脑淀粉样血管病、Braak 神经原纤维缠结阶段、阿尔茨海默病注册研究联盟 (CERAD) 弥漫性斑块评分、CERAD 神经原纤维斑块评分、海马硬化、边缘为主的与年龄相关的 TDP-43 脑病神经病理改变 (LATE-NC) 和路易体病理学。我们将测量值分为三组，描述协调的置信度（低、中、高）。我们描述了神经病理学的患病率、相关性和共同发生。
该队列包括 4354 名 80 岁或以上有尸检数据的死者。所有队列中女性人数均多于男性，只有一项研究只包括男性，所有队列中死者年龄均较大（各队列平均死亡年龄范围为 88.0-91.6 岁）。阿尔茨海默病神经病理学改变、Braak 阶段和 CERAD 评分的测量值处于高置信度类别，而血管神经病理学的测量值处于低（小动脉硬化、动脉粥样硬化、脑淀粉样血管病和腔隙）或中等（大梗塞和微梗塞）类别。神经病理学的患病率和共同发生很高（2695 名参与者中有 2443 名[91%]有 6 种主要神经病理学中的一种以上，1106 名[41%]有 3 种或更多种）。共同发生与痴呆状况呈强烈但非确定性关联。血管和阿尔茨海默病特征在相关分析中单独聚类，LATE-NC 与阿尔茨海默病测量值（例如 Braak 阶段 ρ=0.31[95%CI 0.20-0.42]）有中度关联。
与阿尔茨海默病神经病理学改变的测量相比，血管神经病理学的测量具有更高的变异性和更大的不一致性，这表明开发新的血管神经病理学测量框架可能会有所帮助。结果突出了导致老年人痴呆的大脑病理学的复杂性和多病共存性，并表明预防工作和治疗应该是多方面的。
盖茨风险投资公司。
