Aβ-amyloid deposition is a key feature of Alzheimer's disease, but Consortium to Establish a Registry for Alzheimer's Disease (CERAD) assessment, based on neuritic plaque density, shows a limited relationships to dementia. Thal phase is based on a neuroanatomical hierarchy of Aβ-deposition, and in combination with Braak neurofibrillary tangle staging also allows derivation of primary age-related tauopathy (PART). We sought to determine whether Thal Aβ phase predicts dementia better than CERAD in a population-representative cohort (n = 186) derived from the Cognitive Function and Ageing Study (CFAS). Cerebral amyloid angiopathy (CAA) was quantitied as the number of neuroanatomical areas involved and cases meeting criteria for PART were defined to determine if they are a distinct pathological group within the ageing population. Agreement with the Thal scheme was excellent. In univariate analysis Thal phase performed less well as a predictor of dementia than CERAD, Braak or CAA. Logistic regression, decision tree and linear discriminant analysis were performed for multivariable analysis, with similar results. Thal phase did not provide a better explanation of dementia than CERAD, and there was no additional benefit to including more than one assessment of Aβ in the model. Number of areas involved by CAA was highly correlated with assessment based on a severity score (p < 0.001). The presence of capillary involvement (CAA type I) was associated with higher Thal phase and Braak stage (p < 0.001). CAA was not associated with microinfarcts (p = 0.1). Cases satisfying pathological criteria for PART were present at a frequency of 10.2% but were not older and did not have a higher likelihood of dementia than a comparison group of individuals with similar Braak stage but with more Aβ. They also did not have higher hippocampal-tau stage, although PART was weakly associated with increased presence of thorn-shaped astrocytes (p = 0.048), suggesting common age-related mechanisms. Thal phase is highly applicable in a population-representative setting and allows definition of pathological subgroups, such as PART. Thal phase, plaque density, and extent and type of CAA measure different aspects of Aβ pathology, but addition of more than one Aβ measure does not improve dementia prediction, probably because these variables are highly correlated. Machine learning predictions reveal the importance of combining neuropathological measurements for the assessment of dementia.

中文翻译：

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CFAS 中老化大脑中 Aβ 沉积的流行病学病理学：添加多种 Aβ 衍生措施并不能改善使用逻辑回归和机器学习方法进行的痴呆评估。

Aβ-淀粉样蛋白沉积是阿尔茨海默病的一个关键特征，但基于神经炎斑块密度的阿尔茨海默病登记协会 (CERAD) 评估显示与痴呆的关系有限。Thal 期基于 Aβ 沉积的神经解剖学层次，结合 Braak 神经原纤维缠结分期也允许推导原发性年龄相关 tauopathy (PART)。我们试图确定在来自认知功能和衰老研究 (CFAS) 的具有人口代表性的队列 (n = 186) 中，Thal Aβ 期是否比 CERAD 更好地预测痴呆。脑淀粉样血管病 (CAA) 被量化为所涉及的神经解剖区域的数量，并且定义满足 PART 标准的病例以确定它们是否是老龄人口中不同的病理组。与 Thal 计划的协议非常好。在单变量分析中，Thal 期作为痴呆的预测指标不如 CERAD、Braak 或 CAA 好。对多变量分析进行了逻辑回归、决策树和线性判别分析，结果相似。Thal 期没有提供比 CERAD 更好的痴呆解释，并且在模型中包含一个以上的 Aβ 评估没有额外的好处。CAA 涉及​​的区域数量与基于严重性评分的评估高度相关（p < 0.001）。毛细血管受累（CAA I 型）与更高的 Thal 期和 Braak 期相关（p < 0.001）。CAA 与微梗死无关 (p = 0.1)。满足 PART 病理标准的病例出现频率为 10。2% 但年龄不高且痴呆的可能性不高于具有相似 Braak 阶段但具有更多 Aβ 的个体的对照组。他们也没有更高的海马-tau 阶段，尽管 PART 与刺状星形胶质细胞的存在增加弱相关（p = 0.048），这表明常见的年龄相关机制。Thal 阶段高度适用于具有代表性的人群环境，并允许定义病理亚组，例如 PART。Thal 阶段、斑块密度以及 CAA 的范围和类型测量 Aβ 病理学的不同方面，但添加多个 Aβ 测量并不能改善痴呆预测，可能是因为这些变量高度相关。机器学习预测揭示了结合神经病理学测量对痴呆症评估的重要性。