Venkatesh Shruthi, Wang Linshanshan, Morris Michele, Moro Mohammed, Srivastava Ratnam, Han Yunqing, Patira Riddhi, Berman Sarah, Lopez Oscar, Visweswaran Shyam, Cai Tianrun, Cai Tianxi, Xia Zongqi
medRxiv. 2025 Apr 23:2025.04.22.25326230. doi: 10.1101/2025.04.22.25326230.
Alzheimer's disease (AD) carries a high societal burden inequitably distributed across demographic groups.
To examine differences in readily ascertainable clinical outcomes of AD decline among demographic groups.
Leveraging the electronic health record (EHR) data (1994-2022) of patients with ≥1 diagnosis code for AD or related dementia from two large healthcare systems, we applied a knowledge graph-guided unsupervised phenotyping algorithm to predict AD diagnosis status and validated using gold-standard chart-reviewed and registry-derived diagnosis labels. After excluding patients with <24 months of data or who were admitted to nursing homes prior to AD diagnosis, we performed survival analyses at each healthcare system to assess the time to two readily ascertainable clinical outcomes of AD decline ( nursing home admission, death), stratified by demographic groups and accounting for baseline covariates ( age, gender, race, ethnicity, healthcare utilization, and comorbidities). We then performed a fixed-effects meta-analysis of the survival analysis data from both healthcare systems.
The AD diagnosis phenotyping algorithm demonstrated high accuracy in identifying AD patients across both healthcare systems (AUROC score range: 0.835-0.923). Of the 34,181 AD patients in both healthcare systems (62% women, 90% non-Hispanic White, 80.39±9.28 years of age at AD diagnosis), 32% were admitted to nursing homes and 50% died during follow- up. In the fixed-effect meta-analysis, non-Hispanic White patients had a lower risk of nursing home admission (HR[95% CI]=0.825[0.776-0.877], <0.001) and higher risk of death (HR[95% CI]=1.381[1.283-1.487], <.0001) than racial and ethnic minorities. There was no difference between women and men in their risk of nursing home admission (HR[95% CI]=1.008[0.967-1.050], =.762), but women had a lower risk of death (HR[95% CI]=0.873[0.837-0.910], <.0001) than men.
This study creates two large EHR-based AD cohorts and adds to the real-world evidence of demographic differences in clinical AD decline, which could potentially inform individual clinical management and future public health policies.
阿尔茨海默病(AD)给社会带来了沉重负担,且在不同人群中的分布不均衡。
研究不同人群中AD病情恶化的可轻易确定的临床结局差异。
利用两个大型医疗系统中诊断代码≥1的AD或相关痴呆患者的电子健康记录(EHR)数据(1994 - 2022年),我们应用知识图谱引导的无监督表型分析算法来预测AD诊断状态,并使用金标准图表审查和登记处得出的诊断标签进行验证。在排除数据少于24个月或在AD诊断前入住养老院的患者后,我们在每个医疗系统进行生存分析,以评估达到AD病情恶化的两个可轻易确定的临床结局(入住养老院、死亡)的时间,按人群分层并考虑基线协变量(年龄、性别、种族、民族、医疗利用情况和合并症)。然后我们对两个医疗系统的生存分析数据进行固定效应荟萃分析。
AD诊断表型分析算法在识别两个医疗系统中的AD患者方面显示出高准确性(曲线下面积评分范围:0.835 - 0.923)。两个医疗系统中的34181例AD患者(62%为女性,90%为非西班牙裔白人,AD诊断时年龄为80.39±9.28岁)中,32%入住了养老院,50%在随访期间死亡。在固定效应荟萃分析中,非西班牙裔白人患者入住养老院的风险较低(风险比[95%置信区间]=0.825[0.776 - 0.877],P<0.001),而死亡风险高于少数族裔(风险比[95%置信区间]=1.381[1.283 - 1.487],P<0.0001)。男性和女性入住养老院的风险没有差异(风险比[95%置信区间]=1.008[0.967 - 1.050],P = 0.762),但女性的死亡风险低于男性(风险比[95%置信区间]=0.873[0.837 - 0.910],P<0.0001)。
本研究创建了两个基于EHR的大型AD队列,并增加了AD临床病情恶化人群差异的真实世界证据,这可能为个体临床管理和未来公共卫生政策提供参考。