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基于联合模型预测老年人轻度认知障碍风险的研究

[Research on predicting the risk of mild cognitive impairment in the elderly based on the joint model].

作者信息

Xu J, Yuan M Q, Fang Y

机构信息

School of Public Health, Xiamen University/Key Laboratory of Health Technology Assessment of Fujian Province University, Xiamen 361102, China.

出版信息

Zhonghua Liu Xing Bing Xue Za Zhi. 2022 Feb 10;43(2):269-276. doi: 10.3760/cma.j.cn112338-20210620-00484.

Abstract

To construct and compare the dynamic prediction models of the risk of mild cognitive impairment (MCI) in the elderly based on six different cognitive function scales. Based on longitudinal data from the Alzheimer's Disease Neuroimaging Initiative from 2005 to 2020, Mini-mental state examination (MMSE), functional activities questionnaire (FAQ), Alzheimer's disease assessment scale-cognitive (ADAS-Cog) 11, ADAS-Cog13, ADAS delayed word recall (ADASQ4), and Rey auditory verbal learning test (RAVLT)_immediate were used as longitudinal cognitive function evaluation indicators to assess the longitudinal changes in cognitive function. The joint model was used to analyze association between indicators variation trajectory and survival outcome MCI, and construct the risk prediction model of MCI in the elderly, the linear mixed model was constructed the longitudinal sub-model which described the evolution of a repeated measure over time, a proportional hazards model was constructed the survival sub-model, and the two sub-models were connected through the correlation parameter (). The areas under the receiver operator characteristic curve (AUC) were used to evaluate the predictive efficacy of the model in the follow-up period of (Δ). The starting point was selected at the 30, 42, and 54 month, and the Δ was selected as 15 and 21 months. Based on the prediction model, an example of the research object was selected for dynamic individual predictions of the risk of MCI. Finally, 544 older adults (aged 60 years and above) with normal baseline cognitive status were included, of which 119 cases (21.9%) had MCI during the follow-up process were regarded as the case group, and 425 cases remained normal as the control group. The joint model suggests that the longitudinal trajectories of the six evaluation indicators are all related to the risk of MCI (<0.001). The risk of MCI decreased by 32.3% (=0.677, 95%: 0.541-0.846) and 10.8% (=0.892, 95%: 0.865-0.919) for each one-point increase of MMSE and RAVLT_immediate longitudinal scores. The risk of MCI increased by 53.2% (=1.532, 95%: 1.393-1.686), 36.2% (=1.362, 95%: 1.268-1.462), 23.2% (=1.232, 95%: 1.181-1.285), and 85.1% (=1.851, 95%:1.629-2.104) for each one-point increase of FAQ, ADAS-Cog11, ADAS-Cog13, and ADASQ4 longitudinal scores. AUC results show that RAVLT_immediate (0.760 2) and ADASQ4 (0.755 8) have higher average prediction efficiency, followed by ADAS-Cog13 (0.743 7), ADAS-Cog11 (0.715 3), FAQ (0.700 8) and MMSE (0.629 5). ADASQ4 joint model was used to provide a dynamic individual prediction of the risk of MCI. The average probability of MCI after five years of follow-up and ten years of follow-up in the example individuals were 8% and 40%, respectively. The RAVLT_immediate and ADASQ4 scales, which are only for memory tests, have high accuracy in predicting the risk of MCI. Using the RAVLT_immediate and ADASQ4 scales as longitudinal cognitive function evaluation indicators to construct a joint model, the results can provide a basis for realizing MCI risk prediction for the elderly.

摘要

构建并比较基于六种不同认知功能量表的老年人轻度认知障碍(MCI)风险动态预测模型。基于2005年至2020年阿尔茨海默病神经影像学倡议的纵向数据,简易精神状态检查表(MMSE)、功能活动问卷(FAQ)、阿尔茨海默病评估量表 - 认知部分(ADAS - Cog)11项、ADAS - Cog13项、ADAS延迟单词回忆(ADASQ4)以及雷伊听觉词语学习测验(RAVLT)即时回忆作为纵向认知功能评估指标,以评估认知功能的纵向变化。采用联合模型分析指标变化轨迹与生存结局MCI之间的关联,构建老年人MCI风险预测模型,构建线性混合模型作为描述重复测量随时间演变的纵向子模型,构建比例风险模型作为生存子模型,且两个子模型通过相关参数连接。采用受试者工作特征曲线(AUC)下面积评估模型在随访期(Δ)的预测效能。起始点分别选取在第30、42和54个月,Δ选取为15和21个月。基于预测模型,选取研究对象实例进行MCI风险的动态个体预测。最后,纳入544名基线认知状态正常的老年人(年龄60岁及以上),其中119例(21.9%)在随访过程中发生MCI被视为病例组,425例保持正常作为对照组。联合模型表明,六个评估指标的纵向轨迹均与MCI风险相关(<0.001)。MMSE和RAVLT即时回忆纵向得分每增加1分,MCI风险分别降低32.3%(=0.677,95%:0.541 - 0.846)和10.8%(=0.892,95%:0.865 - 0.919)。FAQ、ADAS - Cog11、ADAS - Cog13和ADASQ4纵向得分每增加1分,MCI风险分别增加53.2%(=1.532,95%:1.393 - 1.686)、36.2%(=1.362,95%:1.268 - 1.462)、23.2%(=1.232,95%:1.181 - 1.285)和85.1%(=1.851,95%:1.629 - 2.104)。AUC结果显示,RAVLT即时回忆(0.760 2)和ADASQ4(0.755 8)具有较高的平均预测效率,其次是ADAS - Cog13(0.743 7)、ADAS - Cog11(0.715 3)、FAQ(0.700 8)和MMSE(0.629 5)。采用ADASQ4联合模型对MCI风险进行动态个体预测。实例个体随访5年和10年后MCI的平均概率分别为8%和40%。仅用于记忆测试的RAVLT即时回忆和ADASQ4量表在预测MCI风险方面具有较高准确性。以RAVLT即时回忆和ADASQ4量表作为纵向认知功能评估指标构建联合模型,结果可为实现老年人MCI风险预测提供依据。

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