Department of Pathology, Stanford University, Stanford, California, USA.
Department of Anesthesiology, Perioperative, and Pain Medicine, Stanford University, Stanford, California, USA.
Alzheimers Dement. 2023 Jul;19(7):3005-3018. doi: 10.1002/alz.12921. Epub 2023 Jan 21.
Post-mortem analysis provides definitive diagnoses of neurodegenerative diseases; however, only a few can be diagnosed during life.
This study employed statistical tools and machine learning to predict 17 neuropathologic lesions from a cohort of 6518 individuals using 381 clinical features (Table S1). The multisite data allowed validation of the model's robustness by splitting train/test sets by clinical sites. A similar study was performed for predicting Alzheimer's disease (AD) neuropathologic change without specific comorbidities.
Prediction results show high performance for certain lesions that match or exceed that of research annotation. Neurodegenerative comorbidities in addition to AD neuropathologic change resulted in compounded, but disproportionate, effects across cognitive domains as the comorbidity number increased.
Certain clinical features could be strongly associated with multiple neurodegenerative diseases, others were lesion-specific, and some were divergent between lesions. Our approach could benefit clinical research, and genetic and biomarker research by enriching cohorts for desired lesions.
尸检分析可明确诊断神经退行性疾病;然而,只有少数疾病可在生前诊断。
本研究采用统计工具和机器学习,利用 381 个临床特征(表 S1),从 6518 名个体的队列中预测 17 种神经病理学病变。多中心数据允许通过按临床地点划分训练/测试集来验证模型的稳健性。还进行了一项类似的研究,用于预测无特定合并症的阿尔茨海默病(AD)神经病理学变化。
预测结果显示,某些与研究注释相匹配或超过研究注释的病变具有较高的性能。除 AD 神经病理学变化之外的神经退行性合并症导致随着合并症数量的增加,认知域的复合但不成比例的影响。
某些临床特征可能与多种神经退行性疾病密切相关,其他特征则是病变特异性的,而某些特征在病变之间存在差异。我们的方法可以通过丰富所需病变的队列,使临床研究、遗传和生物标志物研究受益。