机构：[1]School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150080, China[2]Department of Pathology, The Affiliated Hospital of Weifang MedicalUniversity, Weifang 261053, China[3]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center forBrain Disorders, Capital Medical University, Beijing 100069, China[4]Department of Anesthesiology, The Affiliated Hospital of Weifang Medical University, Weifang 261053, China[5]Chinese Institute for Brain Research, Beijing, China[6]State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of MedicalSciences, Beijing, China[7]Key Laboratory of Cerebral Microcirculation in Universities of Shandong . Department of Neurology, Second Affiliated Hospital . Shandong First MedicalUniversity & Shandong Academy of Medical Sciences, Taian 271000 Shandong, China[8]Beijing Key Laboratory of Hypoxia Translational Medicine, National EngineeringLaboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China首都医科大学宣武医院
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.
基金：
National Natural Science Foundation of China [82071212, 81901181]; Beijing Natural Science Foundation [JQ21022]; Mathematical Tianyuan Fund of the National Natural Science Foundation of China [12026414]; Beijing Ten Thousand Talents Project [2020A15]; Science and Technology Beijing One Hundred Leading Talent Training Project [Z141107001514006]; Beijing Municipal Administration of Hospitals' Mission Plan [SML20150802]; Funds of Academic Promotion Programme of Shandong First Medical University & Shandong Academy of Medical Sciences [2019QL016, 2019PT007]
第一作者机构：[1]School of Computer Science and Technology, Harbin Institute of Technology, Harbin 150080, China
通讯作者：
通讯机构：[3]Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Ministry of Science and Technology, Collaborative Innovation Center forBrain Disorders, Capital Medical University, Beijing 100069, China[5]Chinese Institute for Brain Research, Beijing, China[7]Key Laboratory of Cerebral Microcirculation in Universities of Shandong . Department of Neurology, Second Affiliated Hospital . Shandong First MedicalUniversity & Shandong Academy of Medical Sciences, Taian 271000 Shandong, China[8]Beijing Key Laboratory of Hypoxia Translational Medicine, National EngineeringLaboratory of Internet Medical Diagnosis and Treatment Technology, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
推荐引用方式(GB/T 7714)：
Hu Yang,Zhang Yan,Zhang Haihua,et al.Cognitive performance protects against Alzheimer's disease independently of educational attainment and intelligence[J].MOLECULAR PSYCHIATRY.2022,27(10):4297-4306.doi:10.1038/s41380-022-01695-4.
APA：
Hu, Yang,Zhang, Yan,Zhang, Haihua,Gao, Shan,Wang, Longcai...&Liu, Guiyou.(2022).Cognitive performance protects against Alzheimer's disease independently of educational attainment and intelligence.MOLECULAR PSYCHIATRY,27,(10)
MLA：
Hu, Yang,et al."Cognitive performance protects against Alzheimer's disease independently of educational attainment and intelligence".MOLECULAR PSYCHIATRY 27..10(2022):4297-4306
医学