The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences

The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences | 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 Research Article The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences Ida K Karlsson, Margaret Gatz, Thalida Em Arpawong, Anna K Dahl Aslan, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-186197/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Body mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGS BMI ). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life. The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGS BMI compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline. Epidemiology Geriatrics & Gerontology Psychology obesity cognition epidemiology genetics longitudinal Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Full Text Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and accessed as a PDF. Supplementary Files Supplementarytables.xlsx Table S1-S7 Supplementaryfigures.pdf Figure S1-S3 Cite Share Download PDF Status: Posted Version 1 posted 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-186197","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":9750825,"identity":"de25b2c8-048b-4c2c-8dec-e00c6e5f6d08","order_by":0,"name":"Ida K Karlsson","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2UlEQVRIiWNgGAWjYBACNoYEBsYGBgYZMO/DAQnitfCAOIwziNHCgKyFmecAERr42JMfMM6ouccj33/42GObMxYM8u0NBBzG88yAccOxYh6DG2npxjk3JBgMzhCwik0iwYDxAVsCj4EEj5l0zgegFokEQlrSPzA++JcAdNgZM2kLoBb5+Q8IackxYNzYlsDDcCDHTJoB6DCGG/h1AP3ypuDgzL4EkF/SJHvOSPAYnCHgMPn29I0Pe74lyIFCTOLHsTo5+fYDBKwBAhQlPITVj4JRMApGwSggCAAamT7QoI1tqgAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0000-0003-3605-7829","institution":"Karolinska Institutet","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Ida","middleName":"K","lastName":"Karlsson","suffix":""},{"id":9750826,"identity":"148fa542-4045-4699-9e00-07aa5a7e9f58","order_by":1,"name":"Margaret Gatz","email":"","orcid":"https://orcid.org/0000-0002-1071-9970","institution":"University of Southern California","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Margaret","middleName":"","lastName":"Gatz","suffix":""},{"id":9750827,"identity":"683dcb3a-1fea-4a88-b876-56501e996dbf","order_by":2,"name":"Thalida Em Arpawong","email":"","orcid":"https://orcid.org/0000-0001-9671-9535","institution":"University of Southern California","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Thalida","middleName":"Em","lastName":"Arpawong","suffix":""},{"id":9750828,"identity":"2c21e778-5abe-4992-8930-b84171f91d93","order_by":3,"name":"Anna K Dahl Aslan","email":"","orcid":"https://orcid.org/0000-0002-6305-8993","institution":"Högskolan i Skövde","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Anna","middleName":"K Dahl","lastName":"Aslan","suffix":""},{"id":9750829,"identity":"5acbec53-f623-48b2-aa26-e1550a82f9cd","order_by":4,"name":"Chandra A Reynolds","email":"","orcid":"https://orcid.org/0000-0001-6502-7173","institution":"University of California, Riverside","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Chandra","middleName":"A","lastName":"Reynolds","suffix":""}],"badges":[],"createdAt":"2021-01-29 21:23:30","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":true,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false,"coiExplicitlySet":false},"doi":"10.21203/rs.3.rs-186197/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-186197/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":5512833,"identity":"92272654-6b5b-4c9f-a4fe-965853a36689","added_by":"auto","created_at":"2021-02-01 18:40:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":211715,"visible":true,"origin":"","legend":"Path diagram of the bivariate dual change score model with two slopes, allowing for different rates of change before and after age 70. Body mass index (BMI) and cognitive abilities (COG) in each age category (BMI50, BMI52…; COG50, COG52…) are modeled. From the left, BMI50, BMIS, COG50, and COGS represent intercept level (at age 50) and slope of BMI and cognitive ability (asterisks represent their standardized scores), together with their estimated mean levels (μBMI50, μBMIS, μCOG50, μCOGS) and variances ( δ2BM50, δ2BMIS, δ2COG50, δ2COGS). αBMI and αCOG represent the constant change related to the slopes, and βBMI and βCOG represent the proportional change. γBMI\u003eCOG represent the coupling effect of BMI on cognition, and γCOG\u003eBMI that of cognition on BMI. Univariate change in BMI at age=i,, before age 70, is determined by the sum of the constant change in relation to the slope (αBMI * BMIS) and the proportional change in relation to BMI level at the preceding occasion (βBMI\u003c70 * BMIt-1). For bivariate change in BMI, considering the effect of cognitive ability, the additional coupling effect in relation to cognitive ability at the preceding occasion is added to the formula (γCOG\u003eBMI, \u003c70 * COGt-1). Univariate and bivariate change in BMI after age 70 and in cognitive abilities before and after age 70 is determined by the same formulas, using the corresponding parameters.","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/bc0e2bdbaf04e8e239aea45b.png"},{"id":5512827,"identity":"36cbee68-9b0d-4fe1-ae60-4017e52b476f","added_by":"auto","created_at":"2021-02-01 18:40:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":149654,"visible":true,"origin":"","legend":"Longitudinal trajectories from bivariate dual change score models, showing change in BMI and cognitive abilities with and without the bivariate coupling-parameter. Trajectories from the full coupling model are shown in black, and those from the no-coupling model in grey. Models were adjusted for sex and education, and a breakpoint in the constant change parameter added at age 70 for BMI and mental status, and at 65 for episodic memory and total cognition","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/a8e1180a08189aebfe97de82.png"},{"id":5513143,"identity":"5d577a2b-7a56-44f9-a3a2-97a6a366fc7c","added_by":"auto","created_at":"2021-02-01 18:43:36","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":157173,"visible":true,"origin":"","legend":"Longitudinal trajectories from bivariate dual change score models, showing change in BMI stratified by cognitive ability level at baseline, and change in cognitive abilities stratified by BMI level at baseline. Models were adjusted for sex and education, and a breakpoint in the constant change and coupling parameters added at age 70 for BMI and mental status, and at 65 for episodic memory and total cognition. \nstatus, but that the decline was steeper with a higher BMI (γBMI\u003eCOG=-0.43 both before and after the age 70 breakpoint; Table 1a).\n","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/ce317523195a7eebde307f45.png"},{"id":5513142,"identity":"671ee239-5461-45bf-9878-b89543020d5f","added_by":"auto","created_at":"2021-02-01 18:43:36","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":140685,"visible":true,"origin":"","legend":"Longitudinal trajectories from bivariate dual change score models, showing change in BMI and cognitive abilities for men and women separately. Models were adjusted for education, and a breakpoint in the constant change and coupling parameters added at age 70 for BMI and mental status, and at 65 for episodic memory and total cognition. ","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/8bb2b4d459b259470688cb15.png"},{"id":5512830,"identity":"1fbc16ad-4066-4816-996a-bf79d0b23fcb","added_by":"auto","created_at":"2021-02-01 18:40:36","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":161029,"visible":true,"origin":"","legend":"Longitudinal trajectories from bivariate dual change score models, showing change in BMI and cognitive abilities stratified by genetic predisposition to high, medium, or low BMI. All models were adjusted for sex and education, and a breakpoint in the constant change and coupling parameters was added at age 70 for BMI and mental status, and at 65 for episodic memory and total cognition.","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/c2e5de37f31e4a7a2a2c5294.png"},{"id":13580460,"identity":"5258f5ee-329c-4f3d-a18e-5cf2aa465ad4","added_by":"auto","created_at":"2021-09-17 04:23:40","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1122829,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptBMIcognitionResearchSquare.pdf","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1_covered.pdf"},{"id":5513344,"identity":"1e15856b-4d8e-407c-a777-999f31f71c1f","added_by":"auto","created_at":"2021-02-01 18:49:40","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1323223,"visible":true,"origin":"","legend":"","description":"","filename":"ManuscriptBMIcognitionResearchSquare.pdf","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1_stamped.pdf"},{"id":5512828,"identity":"99c638cc-f96d-494b-983d-b3ddc3b7327b","added_by":"auto","created_at":"2021-02-01 18:40:36","extension":"xlsx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":63088,"visible":true,"origin":"","legend":"Table S1-S7","description":"","filename":"Supplementarytables.xlsx","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/9676efce52fb191ab1d4fdd3.xlsx"},{"id":5513258,"identity":"03086bf6-a7eb-420d-b1f9-d1a613a55e5c","added_by":"auto","created_at":"2021-02-01 18:46:36","extension":"pdf","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":884864,"visible":true,"origin":"","legend":"Figure S1-S3","description":"","filename":"Supplementaryfigures.pdf","url":"https://assets-eu.researchsquare.com/files/rs-186197/v1/20c7ba404eae7e4654045c5e.pdf"}],"financialInterests":"","formattedTitle":"\u003cp\u003eThe dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences\u003c/p\u003e","fulltext":[{"header":"Full Text","content":"Due to technical limitations, full-text HTML conversion of this manuscript could not be completed. However, the latest manuscript can be downloaded and \u003ca href='/article/rs-186197/latest.pdf' target='_blank'\u003e accessed as a PDF.\u003c/a\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Jönköping University","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"obesity, cognition, epidemiology, genetics, longitudinal","lastPublishedDoi":"10.21203/rs.3.rs-186197/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-186197/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBody mass index (BMI) is associated with cognitive abilities, but the nature of the relationship remains largely unexplored. We aimed to investigate the bidirectional relationship from midlife through late-life, while considering sex differences and genetic predisposition to higher BMI. We used data from 23,892 individuals of European ancestry from the Health and Retirement Study, with longitudinal data on BMI and three established cognitive indices: mental status, episodic memory, and their sum, called total cognition. To investigate the dynamic relationship between BMI and cognitive abilities, we applied dual change score models of change from age 50 through 89, with a breakpoint at age 65 or 70. Models were further stratified by sex and genetic predisposition to higher BMI using tertiles of a polygenic score for BMI (PGS\u003csub\u003eBMI\u003c/sub\u003e). We demonstrated bidirectional effects between BMI and all three cognitive indices, with higher BMI contributing to steeper decline in cognitive abilities in both midlife and late-life, and higher cognitive abilities contributing to less decline in BMI in late-life.\u0026nbsp;The effects of BMI on change in cognitive abilities were more evident in men compared to women, and among those in the lowest tertile of the PGS\u003csub\u003eBMI\u003c/sub\u003e compared to those in the highest tertile, while the effects of cognition on BMI were similar across groups. In conclusion, these findings highlight a reciprocal relationship between BMI and cognitive abilities, indicating that the negative effects of a higher BMI persist from midlife through late-life, and that weight-loss in late-life may be driven by cognitive decline.\u003c/p\u003e","manuscriptTitle":"The dynamic association between body mass index and cognition from midlife through late-life, and the effect of sex and genetic influences","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2021-02-01 18:40:34","doi":"10.21203/rs.3.rs-186197/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"4eb0aa82-ef4d-4bb6-aa43-ae780538db2a","owner":[],"postedDate":"February 1st, 2021","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":2158436,"name":"Epidemiology"},{"id":2158437,"name":"Geriatrics \u0026 Gerontology"},{"id":2158438,"name":"Psychology"}],"tags":[],"updatedAt":"2021-02-01T18:40:34+00:00","versionOfRecord":[],"versionCreatedAt":"2021-02-01 18:40:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-186197","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-186197","identity":"rs-186197","version":["v1"]},"buildId":"FbvkV6FR0MCFSLy54lSbu","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}