Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study

Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study | 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 Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study Fannie Bretelle, Frederic Gervais, Virginie Dauphinot, Michel Chuzeville, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8163794/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 5 You are reading this latest preprint version Abstract Background Transthyretin amyloidosis cardiomyopathy (ATTR-CM) and Alzheimer’s disease (AD) are age-related disorders characterized by pathological protein aggregation. Despite shared risk factors and mechanisms, the relationship between ATTR-CM and AD remains poorly understood. Methods We performed a population-based case–control study using the French National Health Data System from 2019 to 2023. Individuals aged 65 years or older diagnosed with ATTR-CM were matched with controls without ATTR-CM by age, sex, hypertension status, and area of residence. The main exposure was a diagnosis of AD within five years preceding the index date (ATTR-CM diagnosis or equivalent for controls). Conditional logistic regression estimated adjusted odds ratios (ORs) for the association between ATTR-CM and AD, accounting for major dementia risk factors including cardiovascular, metabolic, psychiatric, and lifestyle variables. Results Among 96,200 participants (19,240 ATTR-CM cases and 76,960 controls), 28,990 (30.6%) were women, and the mean (SD) age was 82.3 (6.6) years. The adjusted OR for AD among ATTR-CM patients was 0.65 (99% CI, 0.56–0.75), indicating a lower likelihood of AD compared with controls. Conclusions This large nationwide study suggests that ATTR-CM is associated with a reduced risk of AD, warranting further investigation into underlying biological mechanisms or possible diagnostic bias. Health sciences/Biomarkers Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Health sciences/Neurology Health sciences/Risk factors Alzheimer’s disease Transthyretin amyloidosis Amyloidosis Dementia Epidemiology Full Text Additional Declarations Competing interest reported. Independent of this work, Fannie Bretelle is an unpaid sub-investigator for clinical trials sponsored by Novo Nordisk, Medesis Pharma and GlaxoSmithKline. She declares that he has not received any personal funding and has not participated in any remunerated activities. Michel Chuzeville received travel grant from Astra Zeneca, and expert fees from Pfizer, Novartis, Lilly, Astra Zeneca, Bristol Myers Squibb. Antoine Garnier-Crussard is an unpaid sub-investigator or local principal investigator for clinical trials and studies sponsored by UCB Pharma, Biogen, TauRx Therapeutics, Roche, Novo Nordisk, Alzheon, Medesis Pharma, GlaxoSmithKline, and received research grant from Roche, Lilly and Eisai. He declares that he has not received any personal funding and has not participated in any remunerated activities. Other authors have no disclosure to report. Supplementary Files Supplement.docx Cite Share Download PDF Status: Under Review Version 1 posted Reviewers invited by journal 30 Mar, 2026 Editor assigned by journal 28 Mar, 2026 Editor invited by journal 16 Dec, 2025 Submission checks completed at journal 12 Dec, 2025 First submitted to journal 12 Dec, 2025 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-8163794","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":614778893,"identity":"bf905261-f27a-411a-9a6e-fc8ad4c3f8cb","order_by":0,"name":"Fannie Bretelle","email":"","orcid":"","institution":"Charpennes Hospital, Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Fannie","middleName":"","lastName":"Bretelle","suffix":""},{"id":614778895,"identity":"2d50ba2c-d3de-42bc-8a51-e7b315f9ce9c","order_by":1,"name":"Frederic Gervais","email":"","orcid":"","institution":"Charpennes Hospital, Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Frederic","middleName":"","lastName":"Gervais","suffix":""},{"id":614778897,"identity":"6fd575cb-41d4-4693-8bf5-676e189cb183","order_by":2,"name":"Virginie Dauphinot","email":"","orcid":"","institution":"Hospices Civils de Lyon, Lyon 1 University","correspondingAuthor":false,"prefix":"","firstName":"Virginie","middleName":"","lastName":"Dauphinot","suffix":""},{"id":614778898,"identity":"3b5e118d-4fe5-4406-86a3-1a0dcf0f06e0","order_by":3,"name":"Michel Chuzeville","email":"","orcid":"","institution":"Edouard Herriot Hospital, Hospices Civils de Lyon","correspondingAuthor":false,"prefix":"","firstName":"Michel","middleName":"","lastName":"Chuzeville","suffix":""},{"id":614778899,"identity":"7e8da8a1-adb4-41e4-a933-763fe9e470ad","order_by":4,"name":"Isabelle Quadrio","email":"","orcid":"","institution":"Hospices Civils de Lyon, Lyon 1 University","correspondingAuthor":false,"prefix":"","firstName":"Isabelle","middleName":"","lastName":"Quadrio","suffix":""},{"id":614778900,"identity":"952affaa-40ac-41a9-9774-c4c7819f49f8","order_by":5,"name":"Virginie Desestret","email":"","orcid":"","institution":"INSERM U1314/UMR CNRS5284, MeLis Institute","correspondingAuthor":false,"prefix":"","firstName":"Virginie","middleName":"","lastName":"Desestret","suffix":""},{"id":614778901,"identity":"40d943e4-77f3-43ee-b467-72bb5b855e49","order_by":6,"name":"Antoine Garnier-Crussard","email":"data:image/png;base64,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","orcid":"","institution":"Charpennes Hospital, Hospices Civils de Lyon","correspondingAuthor":true,"prefix":"","firstName":"Antoine","middleName":"","lastName":"Garnier-Crussard","suffix":""}],"badges":[],"createdAt":"2025-11-20 10:53:32","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8163794/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8163794/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":106093405,"identity":"a5127249-daae-490b-a426-4677bf7e0ef7","added_by":"auto","created_at":"2026-04-03 11:37:13","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":512382,"visible":true,"origin":"","legend":"","description":"","filename":"Manuscriptrevised.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8163794/v1_covered_a7bed3ff-cba1-45b8-9ef2-ffd8a6638a90.pdf"},{"id":105961381,"identity":"bc9e8a14-f785-42da-8453-8818ecab39d3","added_by":"auto","created_at":"2026-04-01 23:34:25","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":24408,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement.docx","url":"https://assets-eu.researchsquare.com/files/rs-8163794/v1/5feda42981fdad7de5de5f80.docx"}],"financialInterests":"Competing interest reported. Independent of this work, Fannie Bretelle is an unpaid sub-investigator for clinical trials sponsored by Novo Nordisk, Medesis Pharma and GlaxoSmithKline. She declares that he has not received any personal funding and has not participated in any remunerated activities. Michel Chuzeville received travel grant from Astra Zeneca, and expert fees from Pfizer, Novartis, Lilly, Astra Zeneca, Bristol Myers Squibb.\nAntoine Garnier-Crussard is an unpaid sub-investigator or local principal investigator for clinical trials and studies sponsored by UCB Pharma, Biogen, TauRx Therapeutics, Roche, Novo Nordisk, Alzheon, Medesis Pharma, GlaxoSmithKline, and received research grant from Roche, Lilly and Eisai. He declares that he has not received any personal funding and has not participated in any remunerated activities.\nOther authors have no disclosure to report.","formattedTitle":"Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"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":"Alzheimer’s disease, Transthyretin amyloidosis, Amyloidosis, Dementia, Epidemiology","lastPublishedDoi":"10.21203/rs.3.rs-8163794/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8163794/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eTransthyretin amyloidosis cardiomyopathy (ATTR-CM) and Alzheimer\u0026rsquo;s disease (AD) are age-related disorders characterized by pathological protein aggregation. Despite shared risk factors and mechanisms, the relationship between ATTR-CM and AD remains poorly understood.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eWe performed a population-based case\u0026ndash;control study using the French National Health Data System from 2019 to 2023. Individuals aged 65 years or older diagnosed with ATTR-CM were matched with controls without ATTR-CM by age, sex, hypertension status, and area of residence. The main exposure was a diagnosis of AD within five years preceding the index date (ATTR-CM diagnosis or equivalent for controls). Conditional logistic regression estimated adjusted odds ratios (ORs) for the association between ATTR-CM and AD, accounting for major dementia risk factors including cardiovascular, metabolic, psychiatric, and lifestyle variables.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 96,200 participants (19,240 ATTR-CM cases and 76,960 controls), 28,990 (30.6%) were women, and the mean (SD) age was 82.3 (6.6) years. The adjusted OR for AD among ATTR-CM patients was 0.65 (99% CI, 0.56\u0026ndash;0.75), indicating a lower likelihood of AD compared with controls.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThis large nationwide study suggests that ATTR-CM is associated with a reduced risk of AD, warranting further investigation into underlying biological mechanisms or possible diagnostic bias.\u003c/p\u003e","manuscriptTitle":"Cardiac amyloidosis and the risk of Alzheimer's disease: a population-based nested case-control study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-01 23:34:21","doi":"10.21203/rs.3.rs-8163794/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewersInvited","content":"","date":"2026-03-30T16:38:04+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-29T02:46:09+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-12-17T04:03:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-12T14:00:38+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2025-12-12T13:52:44+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":"64daab78-4c7f-4392-bfe5-b8368ec29355","owner":[],"postedDate":"April 1st, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":65417233,"name":"Health sciences/Biomarkers"},{"id":65417234,"name":"Health sciences/Cardiology"},{"id":65417235,"name":"Health sciences/Diseases"},{"id":65417236,"name":"Health sciences/Medical research"},{"id":65417237,"name":"Health sciences/Neurology"},{"id":65417238,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2026-04-01T23:34:21+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-01 23:34:21","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8163794","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8163794","identity":"rs-8163794","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}