Cognitive performance protects against Alzheimer's disease independently of educational attainment and intelligence

被引：39

作者：

Hu, Yang ^{[1
]}

Zhang, Yan ^{[2
]}

Zhang, Haihua ^{[3
]}

Gao, Shan ^{[3
]}

Wang, Longcai ^{[4
]}

Wang, Tao ^{[5
]}

Han, Zhifa ^{[6
]}

Sun, Bao-Liang ^{[7
,8
,9
]}

Liu, Guiyou ^{[3
,5
,7
,8
,9
,10
]}

机构：

[1] Harbin Inst Technol, Sch Comp Sci & Technol, Harbin 150080, Peoples R China

[2] Weifang Med Univ, Affiliated Hosp, Dept Pathol, Weifang 261053, Peoples R China

[3] Capital Med Univ, Collaborat Innovat Ctr Brain Disorders, Beijing Inst Brain Disorders, Lab Brain Disorders,Minist Sci & Technol, Beijing 100069, Peoples R China

[4] Weifang Med Univ, Affiliated Hosp, Dept Anesthesiol, Weifang 261053, Peoples R China

[5] Chinese Inst Brain Res, Beijing, Peoples R China

[6] Chinese Acad Med Sci, Inst Basic Med Sci, State Key Lab Med Mol Biol, Beijing, Peoples R China

[7] Key Lab Cerebral Microcirculat Univ Shandong, Tai An 271000, Shandong, Peoples R China

[8] Second Affiliated Hosp, Dept Neurol, Tai An 271000, Shandong, Peoples R China

[9] Shandong First Med Univ & Shandong Acad Med Sci, Tai An 271000, Shandong, Peoples R China

[10] Capital Med Univ, Xuanwu Hosp, Beijing Key Lab Hypoxia Translat Med, Natl Engn Lab Internet Med Diag & Treatment Techn, Beijing 100053, Peoples R China

来源：

MOLECULAR PSYCHIATRY | 2022年 / 27卷 / 10期

基金：

中国国家自然科学基金; 北京市自然科学基金;

关键词：

GENOME-WIDE ASSOCIATION; MENDELIAN RANDOMIZATION; RISK LOCI; SOCIOECONOMIC-STATUS; IDENTIFIES VARIANTS; COMMON VARIANTS; METAANALYSIS; DECLINE; RESERVE; INTERVENTIONS;

D O I：

10.1038/s41380-022-01695-4

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mendelian-randomization (MR) studies using large-scale genome-wide association studies (GWAS) have identified causal association between educational attainment and Alzheimer's disease (AD). However, the underlying mechanisms are still required to be explored. Here, we conduct univariable and multivariable MR analyses using large-scale educational attainment, cognitive performance, intelligence and AD GWAS datasets. In stage 1, we found significant causal effects of educational attainment on cognitive performance (beta = 0.907, 95% confidence interval (CI): 0.884-0.930, P < 1.145E-299), and vice versa (beta = 0.571, 95% CI: 0.557-0.585, P < 1.145E-299). In stage 2, we found that both increase in educational attainment (odds ratio (OR) = 0.72, 95% CI: 0.66-0.78, P = 1.39E-14) and cognitive performance (OR = 0.69, 95% CI: 0.64-0.75, P = 1.78E-20) could reduce the risk of AD. In stage 3, we found that educational attainment may protect against AD dependently of cognitive performance (OR = 1.07, 95% CI: 0.90-1.28, P = 4.48E-01), and cognitive performance may protect against AD independently of educational attainment (OR = 0.69, 95% CI: 0.53-0.89, P = 5.00E-03). In stage 4, we found significant causal effects of cognitive performance on intelligence (beta = 0.907, 95% CI: 0.877-0.938, P < 1.145E-299), and vice versa (beta = 0.957, 95% CI: 0.937-0.978, P < 1.145E-299). In stage 5, we identified that cognitive performance may protect against AD independently of intelligence (OR = 0.74, 95% CI: 0.61-0.90, P = 2.00E-03), and intelligence may protect against AD dependently of cognitive performance (OR = 1.17, 95% CI: 0.40-3.43, P = 4.48E-01). Collectively, our univariable and multivariable MR analyses highlight the protective role of cognitive performance in AD independently of educational attainment and intelligence. In addition to the intelligence, we extend the mechanisms underlying the associations of educational attainment with AD.

引用

页码：4297 / 4306

页数：10

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