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ORIGINAL RESEARCH ARTICLE

Causal associations between neurodegenerative diseases, cardiovascular diseases, cardiovascular risk factors, and lifestyle factors: Evidence from a Mendelian randomization study

Wanying Jia1 ,  Tianshu Wu2 ,  Yingnan Zhao3 ,  Haiyan Yu1 ,  Hongmei Wang1,4 ,  Dongna Wang1 ,  Tianming Zhang1 ,  Guojie Zang5 ,  Jinwei Liu1,5*
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1 Department of Pharmacy, Chi Feng Municipal Hospital, Chifeng, Inner Mongolia, China
2 Department of Clinical Medicine, The Second Clinical Medical College of Shanxi Medical University, Taiyuan, Shanxi, China
3 Department of Pharmacy, China–Japan Friendship Hospital, Beijing, China
4 Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, Liaoning, China
5 Department of Pharmacy, Chifeng Clinical Medicine College, Inner Mongolia Medical University, Chifeng, Inner Mongolia, China
EJMO, 025180162 https://doi.org/10.36922/EJMO025180162
Received: 30 April 2025 | Revised: 8 June 2025 | Accepted: 7 July 2025 | Published online: 21 August 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Increasing evidence links cardiovascular disorders (CVDs) and related risk factors to neurodegenerative disease development; however, causal mechanisms are poorly defined.

Objective: This study aims to investigate the causal relationships between neurodegenerative diseases, CVDs, and cardiovascular risk factors, as well as the associations between modifiable lifestyle factors and CVDs and their associated risk factors.

Methods: Single-nucleotide polymorphisms demonstrating associations with neurodegenerative disorders, lifestyle factors, and CVDs were extracted from publicly available genome-wide association study databases.

Results: The findings revealed that Alzheimer’s disease (AD) was negatively associated with pulmonary embolism, heart failure, and type 2 diabetes. In addition, Parkinson’s disease (PD) was linked to an increased risk of hypertension and ischemic stroke. Amyotrophic lateral sclerosis (ALS) correlated positively with hypertension and atrial fibrillation; however, it exhibited a negative relationship with peripheral arterial disease. Coffee intake was positively associated with coronary heart disease, peripheral artery disease, and type 2 diabetes. Alcohol intake was linked to elevated risks of coronary heart disease, hypertension, atrial fibrillation, heart failure, myocardial infarction, and type 2 diabetes. In contrast, tea intake demonstrated inverse associations with coronary heart disease and heart failure.

Conclusion: The present study indicates that ALS, PD, coffee intake, and alcohol intake are associated with an elevated risk of CVDs. Conversely, tea intake demonstrated a protective association against the development of CVDs, whereas AD showed inverse associations with certain cardiovascular risk factors. 

Keywords
Alzheimer’s disease
Parkinson’s disease
Amyotrophic lateral sclerosis
Lifestyle factors
Cardiovascular disease
Mendelian randomization
Funding
This study was supported by the Chifeng Natural Science Foundation (SZR24095) and Wu Jieping Medical Foundation Research Project (320.6750.2024-18-13).
Conflict of interest
The authors declared that the research was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest.
References
  1. Vaduganathan M, Mensah GA, Turco JV, Fuster V, Roth GA. The global burden of cardiovascular diseases and risk: A compass for future health. J Am Coll Cardiol. 2022;80(25):2361-2371. doi: 10.1016/j.jacc.2022.11.005

 

  1. Roth GA, Mensah GA, Johnson CO, et al. Global burden of cardiovascular diseases and risk factors, 1990-2019: Update from the GBD 2019 study. J Am Coll Cardiol. 2020;76(25):2982-3021. doi: 10.1016/j.jacc.2020.11.010

 

  1. Awogbindin I, Wanklin M, Verkhratsky A, Tremblay ME. Microglia in neurodegenerative diseases. Adv Neurobiol. 2024;37:497-512. doi: 10.1007/978-3-031-55529-9_27

 

  1. Temple S. Advancing cell therapy for neurodegenerative diseases. Cell Stem Cell. 2023;30(5):512-529. doi: 10.1016/j.stem.2023.03.017

 

  1. Yang J, Tang C. Causal relationship between imaging-derived phenotypes and neurodegenerative diseases: A Mendelian randomization study. Mamm Genome. 2024;35:711-723. doi: 10.1007/s00335-024-10065-0

 

  1. Lee H, Kim E. Repositioning medication for cardiovascular and cerebrovascular disease to delay the onset and prevent progression of Alzheimer’s disease. Arch Pharm Res. 2020;43(9):932-960. doi: 10.1007/s12272-020-01268-5

 

  1. Davies NM, Holmes MV, Davey Smith G. Reading Mendelian randomisation studies: A guide, glossary, and checklist for clinicians. BMJ. 2018;362:k601. doi: 10.1136/bmj.k601

 

  1. Smith GD, Ebrahim S. ‘Mendelian randomization’: Can genetic epidemiology contribute to understanding environmental determinants of disease? Int J Epidemiol. 2003;32(1):1-22. doi: 10.1093/ije/dyg070

 

  1. Davey Smith G, Hemani G. Mendelian randomization: Genetic anchors for causal inference in epidemiological studies. Hum Mol Genet. 2014;23(R1):R89-R98. doi: 10.1093/hmg/ddu328

 

  1. Sekula P, Del Greco MF, Pattaro C, Kottgen A. Mendelian randomization as an approach to assess causality using observational data. J Am Soc Nephrol. 2016;27(11):3253-3265. doi: 10.1681/ASN.2016010098

 

  1. Carter P, Yuan S, Kar S, et al. Coffee consumption and cancer risk: A Mendelian randomisation study. Clin Nutr. 2022;41(10):2113-2123. doi: 10.1016/j.clnu.2022.08.019

 

  1. Fang J, Song K, Zhang D, et al. Coffee intake and risk of diabetic nephropathy: A Mendelian randomization study. Front Endocrinol (Lausanne). 2023;14:1169933. doi: 10.3389/fendo.2023.1169933

 

  1. Skrivankova VW, Richmond RC, Woolf BAR, et al. Strengthening the reporting of observational studies in epidemiology using mendelian randomization: The STROBE-MR statement. JAMA. 2021;326(16):1614-1621. doi: 10.1001/jama.2021.18236

 

  1. Boef AG, Dekkers OM, Le Cessie S. Mendelian randomization studies: A review of the approaches used and the quality of reporting. Int J Epidemiol. 2015;44(2):496-511. doi: 10.1093/ije/dyv071

 

  1. Machiela MJ, Chanock SJ. LDlink: A web-based application for exploring population-specific haplotype structure and linking correlated alleles of possible functional variants. Bioinformatics. 2015;31(21):3555-3557. doi: 10.1093/bioinformatics/btv402

 

  1. Chu H, Wang B, Zhao X, Mu L. Epilepsy and psychiatric comorbidities: A bidirectional mendelian randomization study. J Affect Disord. 2024;350:774-783. doi: 10.1016/j.jad.2024.01.178

 

  1. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: Effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512-525. doi: 10.1093/ije/dyv080

 

  1. Greco MF, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat Med. 2015;34(21):2926-2940. doi: 10.1002/sim.6522

 

  1. Bowden J, Del Greco MF, Minelli C, et al. Improving the accuracy of two-sample summary-data Mendelian randomization: Moving beyond the NOME assumption. Int J Epidemiol. 2019;48(3):728-742. doi: 10.1093/ije/dyy258

 

  1. Yang J, Zhou J, Yang J, et al. Dark chocolate intake and cardiovascular diseases: A Mendelian randomization study. Sci Rep. 2024;14(1):968. doi: 10.1038/s41598-023-50351-6

 

  1. National Center For Cardiovascular Diseases The Writing Committee Of The Report On Cardiovascular Health And Diseases In China. Report on cardiovascular health and diseases in China 2023: An updated summary. Biomed Environ Sci. 2024;37(9):949-992. doi: 10.3967/bes2024.162

 

  1. Xu S, Wen S, Yang Y, et al. Association between body composition patterns, cardiovascular disease, and risk of neurodegenerative disease in the UK biobank. Neurology. 2024;103(4):e209659. doi: 10.1212/WNL.0000000000209659

 

  1. Shukui H, Yitao R, Xin M, et al. Study on the changing trend and forecast of disease burden of Alzheimer’s disease and related dementia in China’s elderly population during 1992 to 2021. Zhong Guo Quan Ke Yi Xue. 2025;28(8):996-1003.

 

  1. Trieu C, Van Harten AC, Leeuwis AE, et al. Alzheimer’s disease and cognitive decline in patients with cardiovascular diseases along the heart-brain Axis. J Alzheimers Dis. 2024;98(3):987-1000. doi: 10.3233/JAD-231096

 

  1. Arega Y, Shao Y. Heart failure and late-onset Alzheimer’s disease: A Mendelian randomization study. Front Genet. 2022;13:1015674. doi: 10.3389/fgene.2022.1015674

 

  1. Cermakova P, Eriksdotter M, Lund LH, Winblad B, Religa P, Religa D. Heart failure and Alzheimer’s disease. J Intern Med. 2015;277(4):406-425. doi: 10.1111/joim.12287

 

  1. Yaribeygi H, Maleki M, Butler AE, Jamialahmadi T, Sahebkar A. Brain insulin signaling and cognition: Possible links. EXCLI J. 2023;22:237-249. doi: 10.17179/excli2023-5841

 

  1. Zhang F, Xian D, Feng J, et al. Causal relationship between Alzheimer’s disease and cardiovascular disease: A bidirectional Mendelian randomization analysis. Aging (Albany NY). 2023;15(17):9022-9040. doi: 10.18632/aging.205013

 

  1. Burillo J, Marques P, Jimenez B, Gonzalez-Blanco C, Benito M, Guillen C. Insulin resistance and diabetes mellitus in Alzheimer’s disease. Cells. 2021;10(5):1236. doi: 10.3390/cells10051236

 

  1. Chen YH, Ren CY, Yu C. Causal relationship between Alzheimer’s disease and unstable angina: A bidirectional Mendelian randomization analysis. Front Psychiatry. 2024;15:1435394. doi: 10.3389/fpsyt.2024.1435394

 

  1. Akyol O, Akyol S, Chou MC, et al. Lipids and lipoproteins may play a role in the neuropathology of Alzheimer’s disease. Front Neurosci. 2023;17:1275932. doi: 10.3389/fnins.2023.1275932

 

  1. Aparicio HJ, Tarko LM, Gagnon D, et al. Low blood pressure, comorbidities, and ischemic stroke mortality in US veterans. Stroke. 2022;53(3):886-894. doi: 10.1161/STROKEAHA.120.033195

 

  1. Karjalainen JP, Mononen N, Hutri-Kahonen N, et al. The effect of apolipoprotein E polymorphism on serum metabolome - a population-based 10-year follow-up study. Sci Rep. 2019;9(1):458. doi: 10.1038/s41598-018-36450-9

 

  1. Zhao T, Zhong T, Zhang M, Xu Y, Zhang M, Chen L. Alzheimer’s disease: Causal effect between obesity and APOE gene polymorphisms. Int J Mol Sci. 2023;24(17):13531. doi: 10.3390/ijms241713531

 

  1. Chen J, Zhang C, Wu Y, Zhang D. Association between hypertension and the risk of Parkinson’s disease: A meta-analysis of analytical studies. Neuroepidemiology. 2019;52(3- 4):181-192. doi: 10.1159/000496977

 

  1. Sheikh AM, Yano S, Tabassum S, Nagai A. The role of the vascular system in degenerative diseases: Mechanisms and implications. Int J Mol Sci. 2024;25(4):2169. doi: 10.3390/ijms25042169

 

  1. Fanciulli A, Gobel G, Ndayisaba JP, et al. Supine hypertension in Parkinson’s disease and multiple system atrophy. Clin Auton Res. 2016;26(2):97-105. doi: 10.1007/s10286-015-0336-4

 

  1. Zhou Z, Zhang M, Fang Q, Huang J. Relationship between Parkinson’s disease and cardio-cerebrovascular diseases: A Mendelian randomized study. Sci Rep. 2023;13(1):20428. doi: 10.1038/s41598-023-47708-2

 

  1. Elfil M, Bayoumi A, Sayed A, et al. Stroke in Parkinson’s disease: A review of epidemiological studies and potential pathophysiological mechanisms. Acta Neurol Belg. 2023;123(3):773-783. doi: 10.1007/s13760-023-02202-4

 

  1. Mitroshina EV, Savyuk MO, Ponimaskin E, Vedunova MV. Hypoxia-inducible factor (HIF) in ischemic stroke and neurodegenerative disease. Front Cell Dev Biol. 2021;9:703084. doi: 10.3389/fcell.2021.703084

 

  1. Dai C, Tan C, Zhao L, et al. Glucose metabolism impairment in Parkinson’s disease. Brain Res Bull. 2023;199:110672. doi: 10.1016/j.brainresbull.2023.110672

 

  1. Umeno A, Biju V, Yoshida Y. In vivo ROS production and use of oxidative stress-derived biomarkers to detect the onset of diseases such as Alzheimer’s disease, Parkinson’s disease, and diabetes. Free Radic Res. 2017;51(4):413-427. doi: 10.1080/10715762.2017.1315114

 

  1. Yao Y, Liu H, Gu Y, Xu X, Zhang X. A causal association between amyotrophic lateral sclerosis and atrial fibrillation: A two-sample Mendelian randomization study. Front Cardiovasc Med. 2024;11:1351495. doi: 10.3389/fcvm.2024.1351495

 

  1. Abdel Magid HS, Topol B, McGuire V, Hinman JA, Kasarskis EJ, Nelson LM. Cardiovascular diseases, medications, and ALS: A population-based case-control study. Neuroepidemiology. 2022;56(6):423-432. doi: 10.1159/000526982

 

  1. Freedman DM, Kuncl RW, Cahoon EK, Rivera DR, Pfeiffer RM. Relationship of statins and other cholesterol-lowering medications and risk of amyotrophic lateral sclerosis in the US elderly. Amyotroph Lateral Scler Frontotemporal Degener. 2018;19(7-8):538-546. doi: 10.1080/21678421.2018.1511731

 

  1. Sapaly D, Cheguillaume F, Weill L, et al. Dysregulation of muscle cholesterol transport in amyotrophic lateral sclerosis. Brain. 2025;148(3):788-802. doi: 10.1093/brain/awae270

 

  1. Zanovello M, Soraru G, Campi C, et al. Brain stem glucose hypermetabolism in amyotrophic lateral sclerosis/ frontotemporal dementia and shortened survival: An 18F-FDG PET/MRI study. J Nucl Med. 2022;63(5):777-784. doi: 10.2967/jnumed.121.262232

 

  1. Karlsborg M, Andersen EB, Wiinberg N, Gredal O, Jorgensen L, Mehlsen J. Sympathetic dysfunction of central origin in patients with ALS. Eur J Neurol. 2003;10(3):229-234. doi: 10.1046/j.1468-1331.2003.00578.x

 

  1. Zhang J, Cao W, Xie J, et al. Metabolic syndrome and risk of amyotrophic lateral sclerosis: Insights from a large-scale prospective study. Ann Neurol. 2024;96(4):788-801. doi: 10.1002/ana.27019

 

  1. Zhang S, Xiang B, Su X, Zhou Y, Zhao Y, Zhou X. Is coffee, tea, and red wine consumption beneficial for individuals with hypertension? Postgrad Med J. 2024;100:603-610. doi: 10.1093/postmj/qgae039

 

  1. Turnbull D, Rodricks JV, Mariano GF, Chowdhury F. Caffeine and cardiovascular health. Regul Toxicol Pharmacol. 2017;89:165-185. doi: 10.1016/j.yrtph.2017.07.025

 

  1. Watanabe T, Kobayashi S, Yamaguchi T, Hibi M, Fukuhara I, Osaki N. Coffee abundant in chlorogenic acids reduces abdominal fat in overweight adults: A randomized, double-blind, controlled trial. Nutrients. 2019;11(7):1617. doi: 10.3390/nu11071617

 

  1. Jeon JS, Kim HT, Jeong IH, et al. Contents of chlorogenic acids and caffeine in various coffee-related products. J Adv Res. 2019;17:85-94. doi: 10.1016/j.jare.2019.01.002

 

  1. Rosoff DB, Davey Smith G, Mehta N, Clarke TK, Lohoff FW. Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study. PLoS Med. 2020;17(12):e1003410. doi: 10.1371/journal.pmed.1003410

 

  1. Millwood IY, Im PK, Bennett D, et al. Alcohol intake and cause-specific mortality: Conventional and genetic evidence in a prospective cohort study of 512 000 adults in China. Lancet Public Health. 2023;8(12):e956-e967. doi: 10.1016/S2468-2667(23)00217-7

 

  1. Keller A, Wallace TC. Tea intake and cardiovascular disease: An umbrella review. Ann Med. 2021;53(1):929-944. doi: 10.1080/07853890.2021.1933164

 

  1. Marcos A, Serra-Majem L, Perez-Jimenez F, Pascual V, Tinahones FJ, Estruch R. Moderate consumption of beer and its effects on cardiovascular and metabolic health: An updated review of recent scientific evidence. Nutrients. 2021;13(3):879. doi: 10.3390/nu13030879

 

  1. Anastasius M, Kockx M, Jessup W, Sullivan D, Rye KA, Kritharides L. Cholesterol efflux capacity: An introduction for clinicians. Am Heart J. 2016;180:54-63. doi: 10.1016/j.ahj.2016.07.005

 

  1. Keller A, Wallace TC. Tea intake and cardiovascular disease: An umbrella review. Ann Med. 2021;53(1):929-944. doi: 10.1080/07853890.2021.1933164

 

  1. Bhandari B, Zeng L, Grafenauer S, Schutte AE, Xu X. Long-term consumption of 6 different beverages and cardiovascular disease-related mortality: A systematic review and meta-analysis of prospective cohort studies. Curr Dev Nutr. 2024;8(3):102095. doi: 10.1016/j.cdnut.2024.102095

 

  1. Custodia A, Ouro A, Romaus-Sanjurjo D, et al. Endothelial progenitor cells and vascular alterations in Alzheimer’s disease. Front Aging Neurosci. 2021;13:811210. doi: 10.3389/fnagi.2021.811210

 

  1. Fang YC, Hsieh YC, Hu CJ, Tu YK. Endothelial dysfunction in neurodegenerative diseases. Int J Mol Sci. 2023;24(3):2909. doi: 10.3390/ijms24032909

 

  1. Mahley RW. Apolipoprotein E: From cardiovascular disease to neurodegenerative disorders. J Mol Med (Berl). 2016;94(7):739-746. doi: 10.1007/s00109-016-1427-y

 

  1. Delbaere Q, Chapet N, Huet F, et al. Anti-inflammatory drug candidates for prevention and treatment of cardiovascular diseases. Pharmaceuticals (Basel). 2023;16(1):78. doi: 10.3390/ph16010078

 

  1. Kizza J, Lewington S, Mappin-Kasirer B, et al. Cardiovascular risk factors and Parkinson’s disease in 500,000 Chinese adults. Ann Clin Transl Neurol. 2019;6(4):624-632. doi: 10.1002/acn3.732

 

  1. Dhana A, DeCarli CS, Dhana K, et al. Cardiovascular health and biomarkers of neurodegenerative disease in older adults. JAMA Netw Open. 2025;8(3):e250527. doi: 10.1001/jamanetworkopen.2025.0527
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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