联合潜在类别模型在轻度认知障碍向认知正常逆转研究中的应用

Application of the Joint Latent Class Model in the Reversion of Mild Cognitive Impairment to Normal Cognition

目的将联合潜在类别模型(joint latent class model,JLCM)应用于轻度认知障碍(mild cognitive impairment,MCI)向认知正常(normal cognition,NC)逆转的研究,为慢性病纵向研究提供方法学借鉴。方法JLCM模型包括三个子模型,潜在类别子模型采用多分类logistic回归用于估计潜在类别,纵向过程子模型采用线性混合模型用于描述纵向认知轨迹,生存过程子模型采用比例风险模型用于拟合认知过程。基于信息准则、后验分类、预测值与观测值的比较和条件独立假定等进行模型拟合优度检验。结果基于JLCM模型将MCI人群分为两个潜在类别,分别包括783人(92.88%)和60(7.12%)。潜在类别子模型显示性别、婚姻状况、APOE4和FAQ对潜在类别的确定具有统计学意义;纵向过程子模型显示男性(β=-0.685,95%CI:-1.144~-0.226)、独身(β=0.743,95%CI:0.200~1.286)、未携带APOE4(β=-1.201,95%CI:-1.636~-0.766)和无日常活动功能障碍(β=-1.868,95%CI:-2.095~-1.641)人群的MMSE得分较高;生存过程子模型显示受教育水平较高(HR=1.264,95%CI:1.134~1.395)、独身(HR=1.593,95%CI:1.286~1.899)和未携带APOE4(HR=0.453,95%CI:0.043~0.862)是MCI患者逆转为NC的保护因素。结论JLCM模型在认知障碍等慢性病研究中具有良好的应用价值。

Objective The joint latent class model(JLCM)was applied to study the reversion of mild cognitive impairment(MCI)to normal cognition(NC),providing a methodology reference for the longitudinal study of chronic diseases.Methods The JLCM model consisted of three sub-models:the latent class sub-model adopted multi-class logistic regression to estimate the latent classes;the longitudinal process sub-model adopted linear mixed model to describe the longitudinal cognitive measurement;and the survival process sub-model adopted proportional risk model to fit the cognitive process.Goodness of fit was based on information criterion,posterior classification,comparison between predicted value and observed value and conditional independence assumption.Results The MCI population was divided into two latent classes based on the JLCM model,including 783(92.88%)and 60(7.12%),respectively.The latent class sub-model showed that gender,marital status,APOE4 and FAQ had statistical significance for the determination of latent classes.The longitudinal process sub-model showed male(β=-0.685,95%CI:-1.144,-0.226),being single(β=0.743,95%CI:0.200,1.286),not carrying APOE4(β=-1.201,95%CI:-1.636,-0.766)and without functional impairment(β=-1.868,95%CI:-2.095,-1.641)had higher MMSE scores.The survival process sub-model showed that high education level(HR=1.264,95%CI:1.134,1.395),being single(HR=1.593,95%CI:1.286,1.899)and not carrying APOE4(HR=0.453,95%CI:0.043,0.862)were protective factors for reversion to NC in MCI patients.Conclusion JLCM model has good application value in the study of chronic diseases such as cognitive impairment.