Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures

Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures Lizhen Han, Yi Zeng, Tao Huang, Jinzhu Jia This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3904969/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background The cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a new method and to investigate the causal inference of cognitive-related lifestyle factors. Method The study sample was derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which included 897 seniors aged 65+. This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level). Results The new causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese seniors ( = 1.883, 95% CI : 0.260–3.564), in which there was no horizontal pleiotropy ( p = 0.370). Conclusion The study provided a new causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method. Biological sciences/Neuroscience/Cognitive ageing Biological sciences/Genetics/Genetic association study Health sciences/Risk factors Physical sciences/Mathematics and computing/Statistics Health sciences/Medical research/Epidemiology Health sciences/Medical research/Genetics research Casual inference ordered multi-categorical exposures cognition exercise senior Full Text Additional Declarations No competing interests reported. Supplementary Files Additionalfile1.docx Additionalfile2.docx Additionalfile3.docx Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 22 Feb, 2024 Reviews received at journal 19 Feb, 2024 Reviewers agreed at journal 09 Feb, 2024 Reviewers invited by journal 07 Feb, 2024 Editor assigned by journal 07 Feb, 2024 Editor invited by journal 04 Feb, 2024 Submission checks completed at journal 04 Feb, 2024 First submitted to journal 28 Jan, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3904969","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":271155385,"identity":"d3b42990-2fa9-4228-a066-f85e65231113","order_by":0,"name":"Lizhen Han","email":"","orcid":"","institution":"Beijing Institute of Heart, Lung and Blood Vessel Diseases","correspondingAuthor":false,"prefix":"","firstName":"Lizhen","middleName":"","lastName":"Han","suffix":""},{"id":271155386,"identity":"d32968b6-0c19-44dd-b087-67aeefec0e61","order_by":1,"name":"Yi Zeng","email":"","orcid":"","institution":"Duke University","correspondingAuthor":false,"prefix":"","firstName":"Yi","middleName":"","lastName":"Zeng","suffix":""},{"id":271155387,"identity":"af4edd2b-bc63-4f8a-9f27-0b81043e3071","order_by":2,"name":"Tao Huang","email":"","orcid":"","institution":"Peking University","correspondingAuthor":false,"prefix":"","firstName":"Tao","middleName":"","lastName":"Huang","suffix":""},{"id":271155388,"identity":"36f3a6f0-27a4-4648-9337-a203b27534a3","order_by":3,"name":"Jinzhu Jia","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA6klEQVRIiWNgGAWjYBACxgaGhAMMFUCWBJgDBAeI0nKGgYGHaC0QfW2kaGHuP/DwwM952+TtpRvYHs5sY5Dju5HA+LkAr8MOJBzs3XbbsEfmALvhxjYGY8kbCczSM/BpaWxIOMC77TZjj0QCm+TDNobEDTcS2Jh58GlpZkg4+HfObXuYlnrCWtoYEg7zNtxOBGsBOizBgKCWHqAWmWO3k3tuJLYbzjgnYTjzzMNmaXxaDPvPJH98U3Pbtn1G8rGHPWU28nzHkw9+xqulgScB4UZwGoBGD04gz8B+AMZmw6tyFIyCUTAKRi4AALajUp53RgcpAAAAAElFTkSuQmCC","orcid":"","institution":"Peking University","correspondingAuthor":true,"prefix":"","firstName":"Jinzhu","middleName":"","lastName":"Jia","suffix":""}],"badges":[],"createdAt":"2024-01-28 07:15:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3904969/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3904969/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50707610,"identity":"41951d58-fac7-44b6-ae43-60b82fbaac13","added_by":"auto","created_at":"2024-02-06 06:38:44","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":420156,"visible":true,"origin":"","legend":"","description":"","filename":"LizhenHanmaindocument.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3904969/v1_covered_76f9e871-4943-4b5d-ad9c-890a0b43719f.pdf"},{"id":50707292,"identity":"45c9a944-70f7-43da-acad-516def3184f0","added_by":"auto","created_at":"2024-02-06 06:30:38","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15139,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile1.docx","url":"https://assets-eu.researchsquare.com/files/rs-3904969/v1/c7d674532f2f83b9fcf29215.docx"},{"id":50707291,"identity":"eeffe584-ff35-43ac-81e9-2e1470ba6e58","added_by":"auto","created_at":"2024-02-06 06:30:38","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":29794,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile2.docx","url":"https://assets-eu.researchsquare.com/files/rs-3904969/v1/3af2ad221129f0b5457f1fef.docx"},{"id":50707293,"identity":"fa5a5657-e39d-4562-9fbf-03b05a9ed555","added_by":"auto","created_at":"2024-02-06 06:30:38","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":2273943,"visible":true,"origin":"","legend":"","description":"","filename":"Additionalfile3.docx","url":"https://assets-eu.researchsquare.com/files/rs-3904969/v1/70ffc7530b285f7677921302.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Casual inference, ordered multi-categorical exposures, cognition, exercise, senior","lastPublishedDoi":"10.21203/rs.3.rs-3904969/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3904969/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe cognitive problems are prominent in the context of global aging, and the traditional Mendelian randomization method is not applicable to ordered multi-categorical exposures. Therefore, we aimed to address this issue through the development of a new method and to investigate the causal inference of cognitive-related lifestyle factors.\u003c/p\u003e\u003ch2\u003eMethod\u003c/h2\u003e \u003cp\u003eThe study sample was derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), which included 897 seniors aged 65+. This study used genome-wide association analysis to screen genetic loci as instrumental variables and innovatively combined maximum likelihood estimation to infer causal associations between ordered multi-categorical exposures (diet, exercise, etc.) and continuous outcomes (cognitive level).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe new causal inference method for ordered multi-categorical exposures developed in this study was simple, easy to implement, and able to effectively and reliably discover the potential causal associations between variables. Through this method, we found a potential positive causal association between exercise status and cognitive level in Chinese seniors ( = 1.883, 95%\u003cem\u003eCI\u003c/em\u003e: 0.260\u0026ndash;3.564), in which there was no horizontal pleiotropy (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.370).\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe study provided a new causal inference method applicable to ordered multi-categorical exposures, that addressed the limitations of the traditional Mendelian randomization method.\u003c/p\u003e","manuscriptTitle":"Exercise delayed cognitive decline in Chinese seniors: a new causal inference method for ordered multi-categorical exposures","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-06 06:30:33","doi":"10.21203/rs.3.rs-3904969/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-23T03:53:25+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-19T08:57:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"e99603f9-e252-4ace-8eec-9883e4283bc4","date":"2024-02-09T13:26:53+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-07T05:34:50+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-07T05:24:34+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-02-04T07:33:21+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-02-04T07:31:14+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-01-28T07:01:39+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"9afe6c4a-cf7b-4502-9bd9-7a74d103df6c","owner":[],"postedDate":"February 6th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":28579013,"name":"Biological sciences/Neuroscience/Cognitive ageing"},{"id":28579014,"name":"Biological sciences/Genetics/Genetic association study"},{"id":28579015,"name":"Health sciences/Risk factors"},{"id":28579016,"name":"Physical sciences/Mathematics and computing/Statistics"},{"id":28579017,"name":"Health sciences/Medical research/Epidemiology"},{"id":28579018,"name":"Health sciences/Medical research/Genetics research"}],"tags":[],"updatedAt":"2024-04-09T08:57:16+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-06 06:30:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3904969","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3904969","identity":"rs-3904969","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}