不同MMSE评分下阿尔兹海默病发病风险因素的贝叶斯分位数回归联合模型分析

doi:10.13481/j.1671-587X.20230216

Abstract

Abstract:

Objective To discuss the influencing factors for the risk of Alzheimer’s disease （AD） after correction the Mini-Mental State Examination （MMSE） score trajectory， and to clarify the risk factors for of AD in the people with different MMSE scores. Methods The follow-up data from 2005－2016 were collected based on the AD Neuroimaging Program Database. After screening， the follow-up data of 425 people were finally included， and the variables were screened by LASSO method； the influencing factors of MMSE scores at different quantiles were analyzed by Bayesian quantile regression model， and COX model and Bayesian quantile regression joint model were used to analyze the main risk factors of AD. Results After screening， 10 variables were included， including albumin， total cholesterol， and blood glucose concentration and so on. The results of longitudinal sub-model analysis of the Bayesian quantile regression joint model showed that the influencing factors which affecting the change of MMSE score trajectory at different quartiles were the same， such as albumin， blood glucose concentration， age， gender，apolipoprotein E（APOE4） gene， race， and educational score. The Cox regression sub-model anslysis of the joint model results showed that race and APOE4 gene had the effects on the AD at all quartiles， and the risk ratios of APOE4 gene were 2.188（（95%CI：1.775，2.620）， 1.751（95%CI：1.422，2.042）， 1.706（95%CI：1.391，2.102）， and 2.056（95%CI：1.439，3.206）.The total cholesterol level and history had the effects on the AD only at parts of quartiles. Conclusion The risk factors of AD are different in the people with different MMSE score distributions， and the degree of influencing are also different. Both APOE4 gene and whiteness are the risk factors of AD at different quartiles， and the total cholesterol level and history are the risk factors of AD only at parts of quartiles.

Key words: Bayesian quantile regression joint model, Quantile regression model, Cox model, Alzheimer’s disease, Mini-Mental State Examination, Risk factor

CLC Number:

R749.16

Lianyuan WANG,Yi YANG,Huiwen CONG,Haohua WANG,Qihan BAO,Chengsheng LI,Liwen ZHOU,Zichen DING,Yanli LI,Fuyan SHI,Suzhen WANG. Bayesian quantile regression joint model analysis on risk factors of Alzheimer’s disease in people with different MMSE scores[J].Journal of Jilin University(Medicine Edition), 2023, 49(2): 395-401.

Figures/Tables 7

Tab.1

Fig. 1

Tab.2

Fig. 2

Tab. 3

Tab.4

Tab.5

Longitudinal sub-model of bayesian quantile regression joint model analysis on 425 followers"

Model	β（95%CI）
Model	τ=0.15	τ=0.25	τ=0.75	τ=0.85
Albumin	0.084(0.066－0.098)^*	0.069(0.050－0.082)^*	0.063(0.038－0.081)^*	0.063(0.049－0.076)^*
Glucose	－0.327(－0.353－－0.290)^*	－0.175(－0.209－－0.148)^*	－0.212(－0.267－－0.182)^*	－0.205(－0.262－－0.143)^*
Age	－0.057(－0.070－－0.047)^*	－0.060(－0.068－－0.052)^*	－0.033(－0.041－－0.021)^*	－0.030(－0.036－－0.023)^*
APOE4 gene(Yes vs No)	－0.586(－0.625－－0.532)^*	－0.535(－0.584－－0.471)^*	－0.607(－0.651－－0.570)^*	－0.602(－0.662－－0.537)^*
Gender(Male vs Female)	0.712(0.683－0.742)^*	0.696(0.625－0.759)^*	0.659(0.601－0.705)^*	0.646(0.616－0.664)^*
Educational score	0.159(0.132－0.186)^*	0.168(0.149－0.186)^*	0.109(0.087－0.134)^*	0.104(0.085－0.127)^*
Race(White vs Other)	0.662(0.638－0.693)^*	0.540(0.456－0.623)^*	0.683(0.653－0.712)^*	0.626(0.580－0.677)^*
Survival
Age at baseline	－0.001(－0.025－0.022)	－0.001(－0.027－0.024)	0.022(－0.013－0.060)	0.004(－0.023－0.032)
APOE4 gene(Yes vs No)	0.783(0.574－0.963)^*	0.560(0.352－0.714)^*	0.534(0.330－0.743)^*	0.721(0.364－1.165)^*
Race(White vs Other)	－1.582(－1.873－－1.425)^*	－1.473(－1.787－－1.199)^*	－1.607(－1.803－－1.440)^*	－1.542(－1.951－－1.193)^*
History(Yes vs No)	0.036(－0.224－0.346)	0.166(－0.053－0.378)	0.545(0.143－0.947)^*	0.224(0.089－0.397)^*
Systolic pressure at baseline	－0.001(－0.014－0.009)	－0.004(－0.016－0.009)	0.002(－0.013－0.016)	－0.002(－0.014－0.012)
Blood glucose at baseline	－0.168(－0.317－0.002)	－0.079(－0.184－0.042)	－0.091(－0.228－0.030)	－0.016(－0.157－0.160)
Total cholesterol at baseline	－0.157(－0.368－0.046)	－0.302(－0.472－－0.126)^*	－0.265(－0.463－－0.064)^*	－0.251(－0.402－－0.095)^*
Albumin at baseline	－0.056(－0.108－0.003)	－0.045(－0.101－0.013)	0.023(－0.055－0.129)	－0.036(－0.098－0.046)

Tab.5

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Variable	Data
Time of follow-up (year)	1.85±1.43
Number of mean follow-up	2.55±0.69
MMSE score	27.69±2.69
Age (year）	72.06±7.24
Educational score	16.50±2.61
Diastolic pressure (P/mmHg)	73.75±9.98
Systolic pressure (P/mmHg)	134.14±16.31
Blood glucose[c_B/（mmol·L^－1）]	5.40±1.05
Total cholesterol [c_B/(mmol·L^－1)]	4.95±0.95
Total triglycerides [c_B/(mmol·L^－1)]	1.19±0.54
Albumin [ρ_B/(g·L^－1)]	40.93±3.04
Gender
Male	223（52.47）
Female	202（47.53）
Marital status
Married	312（73.41）
Other	113（26.59）
Race
White	399(93.89)
Other	26(6.11)
APOE4 gene
Yes	152（35.76）
No	273（64.24）
Family history
Yes	243（57.18）
No	182（42.82）

Variable	τ=0.15		τ=0.25		τ=0.75		τ=0.85
Variable	β	P	β	P	β	P	β	P
Albumin	0.093	0.008	0.010	0.001	0.082	0.011	0.084	0.003
Total cholesterol	－0.337	0.064	－0.334	0.113	－0.337	0.083	－0.335	0.062
Glucose	－0.283	0.001	－0.287	0.002	－0.282	0.002	－0.279	0.001
Systolic pressure	－0.004	0.408	0.002	0.687	0.0003	0.951	－0.003	0.581
Age	－0.059	<0.001	－0.066	<0.001	－0.033	0.040	－0.022	0.192
Educational score	0.156	0.002	0.146	0.007	0.155	0.001	0.153	0.003
APOE4 gene (Yes vs No）	－0.655	0.002	－0.651	0.005	－0.652	0.015	－0.651	0.006
History (Yes vs No）	0.306	0.177	0.304	0.219	0.309	0.247	0.310	0.226
Gender (Male vs Female)	0.672	0.017	0.676	0.066	0.674	0.016	0.674	0.036
Race (White vs Other)	0.705	0.068	0.706	0.092	0.705	0.075	0.704	0.034

Variable	β	HR(95%CI)	P
Age	0.012	1.012（0.977－1.048）	0.516
Gender（Male vs Female）	－0.338	0.713（0.399－1.274）	0.253
Educational score	－0.006	0.994（0.901－1.097）	0.909
Race（White vs Other）	－1.466	0.231（0.032－1.675）	0.147
Marry (Married vs Other)	－0.174	0.840（0.445－1.585）	0.591
History（Yes vs No）	0.302	1.352（0.804－2.273）	0.255
APOE4 gene（Yes vs No）	0.776	2.174（1.340－3.527）	0.002
Systolic pressure at baseline	0.001	1.001（0.988－1.014）	0.885
Glucose at baseline	－0.054	0.947（0.751－1.196）	0.650
Total cholesterol at baseline	－0.147	0.863（0.651－1.144）	0.306
Albumin at baseline	－0.036	0.965（0.886－1.051）	0.410

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Bayesian quantile regression joint model analysis on risk factors of Alzheimer’s disease in people with different MMSE scores

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Variable	Assignment
Age (year）	－
Educational score	－
Systolic pressure	－
Blood glucose	－
Total cholesterol	－
Albumin	－
Gender	1=Male, 2=Female
Race	1=White, 2=Other
APOE4 gene	1=No, 2=Yes
History	1=No, 2=Yes
“－”:Variables were continuous variables.