Fan Peihao, Miranda Oshin, Qi Xiguang, Kofler Julia, Sweet Robert A, Wang Lirong
Computational Chemical Genomics Screening Center, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Department of Pathology, Division of Neuropathology, UPMC Presbyterian Hospital, Pittsburgh, PA 15213, USA.
Pharmaceuticals (Basel). 2023 Jun 21;16(7):911. doi: 10.3390/ph16070911.
Around 50% of patients with Alzheimer's disease (AD) may experience psychotic symptoms after onset, resulting in a subtype of AD known as psychosis in AD (AD + P). This subtype is characterized by more rapid cognitive decline compared to AD patients without psychosis. Therefore, there is a great need to identify risk factors for the development of AD + P and explore potential treatment options. In this study, we enhanced our deep learning model, DeepBiomarker, to predict the onset of psychosis in AD utilizing data from electronic medical records (EMRs). The model demonstrated superior predictive capacity with an AUC (area under curve) of 0.907, significantly surpassing conventional risk prediction models. Utilizing a perturbation-based method, we identified key features from multiple medications, comorbidities, and abnormal laboratory tests, which notably influenced the prediction outcomes. Our findings demonstrated substantial agreement with existing studies, underscoring the vital role of metabolic syndrome, inflammation, and liver function pathways in AD + P. Importantly, the DeepBiomarker model not only offers a precise prediction of AD + P onset but also provides mechanistic understanding, potentially informing the development of innovative treatments. With additional validation, this approach could significantly contribute to early detection and prevention strategies for AD + P, thereby improving patient outcomes and quality of life.
约50%的阿尔茨海默病(AD)患者在发病后可能会出现精神症状,从而形成一种AD的亚型,即AD伴精神病(AD + P)。与无精神病的AD患者相比,这种亚型的特点是认知衰退更快。因此,迫切需要确定AD + P发生的风险因素并探索潜在的治疗方案。在本研究中,我们改进了深度学习模型DeepBiomarker,利用电子病历(EMR)数据来预测AD患者精神病的发作。该模型表现出卓越的预测能力,曲线下面积(AUC)为0.907,显著超过传统风险预测模型。利用基于扰动的方法,我们从多种药物、合并症和异常实验室检查中识别出关键特征,这些特征对预测结果有显著影响。我们的研究结果与现有研究高度一致,强调了代谢综合征、炎症和肝功能途径在AD + P中的重要作用。重要的是,DeepBiomarker模型不仅能精确预测AD + P的发作,还能提供机制理解,可能为创新治疗的开发提供信息。通过进一步验证,这种方法可为AD + P的早期检测和预防策略做出重大贡献,从而改善患者的预后和生活质量。