Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Neurobiol Aging. 2018 May;65:98-108. doi: 10.1016/j.neurobiolaging.2018.01.009. Epub 2018 Jan 31.
There is increasing evidence showing that brain atrophy varies between patients with Alzheimer's disease (AD), suggesting that different anatomical patterns might exist within the same disorder. We investigated AD heterogeneity based on cortical and subcortical atrophy patterns in 299 AD subjects from 2 multicenter cohorts. Clusters of patients and important discriminative features were determined using random forest pairwise similarity, multidimensional scaling, and distance-based hierarchical clustering. We discovered 2 typical (72.2%) and 3 atypical (28.8%) subtypes with significantly different demographic, clinical, and cognitive characteristics, and different rates of cognitive decline. In contrast to previous studies, our unsupervised random forest approach based on cortical and subcortical volume measures and their linear and nonlinear interactions revealed more typical AD subtypes with important anatomically discriminative features, while the prevalence of atypical cases was lower. The hippocampal-sparing and typical AD subtypes exhibited worse clinical progression in visuospatial, memory, and executive cognitive functions. Our findings suggest there is substantial heterogeneity in AD that has an impact on how patients function and progress over time.
越来越多的证据表明，阿尔茨海默病（AD）患者的脑萎缩存在差异，这表明在同一疾病中可能存在不同的解剖模式。我们基于 2 个多中心队列中的 299 名 AD 患者的皮质和皮质下萎缩模式，研究了 AD 的异质性。使用随机森林两两相似性、多维标度和基于距离的层次聚类确定了患者聚类和重要鉴别特征。我们发现了 2 种典型（72.2%）和 3 种非典型（28.8%）亚型，它们具有明显不同的人口统计学、临床和认知特征，以及不同的认知衰退速度。与之前的研究不同，我们基于皮质和皮质下体积测量及其线性和非线性相互作用的无监督随机森林方法揭示了更多具有重要解剖学鉴别特征的典型 AD 亚型，而非典型病例的患病率较低。海马保留和典型 AD 亚型在视空间、记忆和执行认知功能方面的临床进展更差。我们的研究结果表明，AD 存在很大的异质性，这会影响患者随着时间的推移的功能和进展方式。
