欧洲人群饮食因素与认知功能障碍关系的孟德尔随机化分析

doi:10.6040/j.issn.1671-7554.0.2024.1091

摘要/Abstract

摘要： 目的探讨饮食因素与认知功能的可能因果效应。方法利用全基因组关联研究(genome-wide association studies, GWAS)数据,采用逆方差加权法(inverse-variance weighted, IVW)、加权中位数(weighted median, WM)、MR Egger回归(MR-Egger regression)进行孟德尔随机化(Mendelian randomization, MR)分析,评估饮食因素与认知功能的因果关系。同时,进行异质性检验、敏感性分析、多效性分析。结果奶酪摄入量(IVW: OR=1.92, 95%CI: 1.54~2.40, P<0.01)、干果摄入量(IVW: OR=1.64, 95%CI: 1.07~2.53, P=0.03)与认知功能存在正向因果关系,酒精摄入频率(IVW: OR=0.79, 95%CI: 0.71~0.87, P<0.01)、猪肉摄入量(IVW: OR=0.47, 95%CI: 0.24~0.91, P=0.03)与认知功能呈负相关。且所有结果均不存在多效性,留一法亦提示所得结果稳健。其他饮食因素未发现与认知功能具有因果关系。结论奶酪摄入量、干果摄入量增加与认知功能障碍风险降低有关,酒精摄入频率、猪肉摄入量增加与认知功能障碍风险增加有关,但仍需更大的GWAS数据进一步验证这种关系,同时研究其中潜在关联机制,以支持该结论。此外,其他饮食因素未发现与认知功能具有因果关系。

关键词: 饮食因素, 奶酪, 干果, 酒精, 猪肉, 认知功能, 孟德尔随机化

Abstract: Objective To explore the potential causal effects of dietary factors on cognitive function. Methods Utilizing genome-wide association studies(GWAS)data, Mendelian randomization analysis was conducted to assess the causal relationship between dietary factors and cognitive function, employing the inverse-variance weighted(IVW), weighted median, and MR-Egger regression. Heterogeneity tests, sensitivity analyses, and pleiotropy analyses were also performed. Results The results demonstrated positive causal relationships between cognitive function and cheese consumption(IVW: OR=1.92, 95%CI: 1.54-2.40, P<0.001)as well as dried fruit intake(IVW: OR=1.64, 95%CI: 1.07-2.53, P=0.03). Conversely, negative causal relationships were observed between cognitive function and alcohol consumption frequency(IVW: OR=0.79, 95%CI: 0.71-0.87, P<0.001)as well as pork intake(IVW: OR=0.47, 95%CI: 0.24-0.91, P=0.03). No pleiotropy was detected in all results, and the leave-one-out method suggested the robustness of the findings. No causal relationship was found between other dietary factors and cognitive function. Conclusion Increased consumption of cheese and dried fruits are associated with a reduced risk of cognitive impairment, while higher frequency of alcohol consumption and increased pork intake are associated with an elevated risk of cognitive impairment. However, larger GWAS datasets are still needed to further validate these relationships, along with studies investigating the potential underlying mechanisms to support these conclusions. Additionally, no significant causal relationships are observed between other dietary factors and cognitive function.

Key words: Dietary factors, Cheese, Dried fruit, Alcohol, Pork, Cognitive function, Mendelian randomization

中图分类号:

R395

李建锋,张展,丁新华,高奋堂,何勤利,谢萍. 欧洲人群饮食因素与认知功能障碍关系的孟德尔随机化分析[J]. 山东大学学报 (医学版), 2025, 63(4): 36-43.

LI Jianfeng, ZHANG Zhan, DING Xinhua, GAO Fentang, HE Qinli, XIE Ping. Mendelian randomization analysis of dietary factors and cognitive impairment in European populations[J]. Journal of Shandong University (Health Sciences), 2025, 63(4): 36-43.

参考文献

[1] Vishwanath S, Hopper I, Wolfe R, et al. Cognitive trajectories and incident dementia after a cardiovascular event in older adults[J]. Alzheimers Dement, 2023, 19(8): 3670-3678.
[2] Kang YJ, Xue YQ, Shin JH, et al. Human mini-brains for reconstituting central nervous system disorders[J]. Lab Chip, 2023, 23(5): 964-981.
[3] World Health Organization.WHO Guidelines Approved by the Guidelines Review Committee, in Risk Reduction of Cognitive Decline and Dementia: WHO Guidelines[R]. Geneva, 2019.
[4] Sebastian MJ, Khan SK, Pappachan JM, et al. Diabetes and cognitive function: an evidence-based current perspective[J]. World J Diabetes, 2023, 14(2): 92-109.
[5] Dalile B, Kim C, Challinor A, et al. The EAT-Lancet reference diet and cognitive function across the life course[J]. Lancet Planet Health, 2022, 6(9): 749-759.
[6] Hoscheidt S, Sanderlin AH, Baker LD, et al. Mediterranean and Western diet effects on Alzheimers disease biomarkers, cerebral perfusion, and cognition in mid-life: a randomized trial[J]. Alzheimers Dement, 2022, 18(3): 457-468.
[7] Jiwani R, Robbins R, Neri A, et al. Effect of dietary intake through whole foods on cognitive function: review of randomized controlled trials[J]. Curr Nutr Rep, 2022, 11(2): 146-160.
[8] Ference BA, Holmes MV, Smith GD. Using mendelian randomization to improve the design of randomized trials[J]. Cold Spring Harb Perspect Med, 2021, 11(7): a040980. doi:10.1101/cshperspect.a040980
[9] Burgess S, Labrecque JA. Mendelian randomization with a binary exposure variable: interpretation and presentation of causal estimates[J]. Eur J Epidemiol, 2018, 33(10): 947-952.
[10] Botelho J, Machado V, Mendes JJ, et al. Causal association between periodontitis and Parkinsons disease: a bidirectional mendelian randomization study[J]. Genes(Basel), 2021, 12(5): 772. doi:10.3390/genes12050772
[11] Zheng GQ, Chattopadhyay S, Sundquist J, et al. Antihypertensive drug targets and breast cancer risk: a two-sample Mendelian randomization study[J]. Eur J Epidemiol, 2024, 39(5): 535-548.
[12] Grant AJ, Burgess S. Pleiotropy robust methods for multivariable Mendelian randomization[J]. Stat Med, 2021, 40(26): 5813-5830.
[13] Solfrizzi V, Agosti P, Lozupone M, et al. Nutritional intervention as a preventive approach for cognitive-related outcomes in cognitively healthy older adults: a systematic review[J]. J Alzheimers Dis, 2018, 64(1): 229-254.
[14] Jennings A, Cunnane SC, Minihane AM. Can nutrition support healthy cognitive ageing and reduce dementia risk?[J]. BMJ, 2020, 369: 2269. doi:10.1136/bmj.m2269
[15] 张展, 李建锋, 李燕玲, 等. 饮食因素与子痫前期因果关系的孟德尔随机化分析[J]. 山东大学学报(医学版), 2024, 62(8): 59-66. ZHANG Zhan, LI Jianfeng, LI Yanling, et al. Mendelian randomization analysis of causality between dietary factors and preeclampsia[J]. Journal of Shandong University(Health Science), 2024, 62(8): 59-66.
[16] Kim H, Osuka Y, Kojima N, et al. Inverse association between cheese consumption and lower cognitive function in Japanese community-dwelling older adults based on a cross-sectional study[J]. Nutrients, 2023, 15(14): 3181. doi:10.3390/nu15143181
[17] de Goeij LC, van de Rest O, Feskens EJM, et al. Associations between the intake of different types of dairy and cognitive performance in Dutch older adults: the B-PROOF study[J]. Nutrients, 2020, 12(2): 468. doi:10.3390/nu12020468
[18] Ylilauri MPT, Hantunen S, Lönnroos E, et al. Associations of dairy, meat, and fish intakes with risk of incident dementia and with cognitive performance: the Kuopio Ischaemic Heart Disease Risk Factor Study(KIHD)[J]. Eur J Nutr, 2022, 61(5): 2531-2542.
[19] Bara c M, Sari c Z, Vu ci c T, et al. Effect of ripening in brine and in a vacuum on protein, fatty acid and mineral profiles, and antioxidant potential of reduced-fat white cheese[J]. Food Technol Biotechnol, 2021, 59(1): 44-55.
[20] Zhou L, Bai X, Huang JG, et al. Vitamin B12 supplementation improves cognitive function in middle aged and elderly patients with cognitive impairment[J]. Nutr Hosp, 2023, 40(4): 724-731.
[21] Kim CS, Cha LN, Sim M, et al. Probiotic supplementation improves cognitive function and mood with changes in gut microbiota in community-dwelling older adults: a randomized, double-blind, placebo-controlled, multicenter trial[J]. J Gerontol A Biol Sci Med Sci, 2021, 76(1): 32-40.
[22] Esselun C, Dilberger B, Silaidos CV, et al. A walnut diet in combination with enriched environment improves cognitive function and affects lipid metabolites in brain and liver of aged NMRI mice[J]. Neuromolecular Med, 2021, 23(1): 140-160.
[23] Bolling BW, Aune D, Noh H, et al. Dried fruits, nuts, and cancer risk and survival: a review of the evidence and future research directions[J]. Nutrients, 2023, 15(6): 1443. doi:10.3390/nu15061443
[24] Ros E, Singh A, OKeefe JH. Nuts: natural pleiotropic nutraceuticals[J]. Nutrients, 2021, 13(9): 3269. doi:10.3390/nu13093269
[25] Datlow LY, King J, Leventhal M, et al. Association of pork intake with cognitive performance in older adults enrolled in the national health and nutrition examination survey(NHANES), 2011-2014 data cycles[J]. J Alzheimers Dis, 2023, 96(1): 351-358.
[26] Zhang HF, Cade J, Hadie L. Consumption of red meat is negatively associated with cognitive function: a cross-sectional analysis of UK biobank[J]. Curr Dev Nutr, 2020, 4: nzaa061_138. doi:10.1093/cdn/nzaa061_138
[27] Daviet R, Aydogan G, Jagannathan K, et al. Associations between alcohol consumption and gray and white matter volumes in the UK Biobank[J]. Nat Commun, 2022, 13(1): 1175. doi:10.1038/s41467-022-28735-5
[28] Zhang RY, Shen LQ, Miles T, et al. Association of low to moderate alcohol drinking with cognitive functions from middle to older age among US adults[J]. JAMA Netw Open, 2020, 3(6): e207922. doi:10.1001/jamanetworkopen.2020.7922
[29] Bucur IG, Claassen T, Heskes T. Inferring the direction of a causal link and estimating its effect via a Bayesian Mendelian randomization approach[J]. Stat Methods Med Res, 2020, 29(4): 1081-1111.

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