Blood Biomarkers and MoCA Scores in MCI and Dementia: The Role of Homocysteine and Hemoglobin in Domain-Specific Cognitive Impairment

Blood Biomarkers and MoCA Scores in MCI and Dementia: The Role of Homocysteine and Hemoglobin in Domain-Specific Cognitive Impairment | 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 Blood Biomarkers and MoCA Scores in MCI and Dementia: The Role of Homocysteine and Hemoglobin in Domain-Specific Cognitive Impairment Parmida Hajipour, Kiana Orangi, Ghazal tavakoli, Mostafa Almasi-Dooghaee, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7409150/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 Background Serum biomarkers offer a non-invasive approach to support early cognitive assessment, but their association with cognitive function across dementia stages remains unclear. The Montreal Cognitive Assessment (MoCA) is a well-known screening tool, yet its reflection of underlying biochemical changes, particularly in specific cognitive domains, has been less explored. Objective This study investigated the relationship between MoCA scores and plasma levels of homocysteine, hemoglobin, vitamin B12, folate, and vitamin D in individuals with mild cognitive impairment (MCI) or dementia, and whether these biomarkers explained domain-specific cognitive differences. Methods A retrospective cross-sectional study was conducted on 240 individuals aged ≥ 50 years with clinically diagnosed MCI or dementia. MoCA version 7.1 was administered, and biomarker levels were obtained from hospital records. Correlation and group comparison analyses were applied to assess associations between biomarker concentrations, MoCA performance, and dementia subtypes. Results Poorer performance in the executive and visuospatial domains, such as clock drawing and serial subtraction, and lower MoCA scores were linked to elevated homocysteine levels (p < 0.01). MoCA scores showed a positive correlation with higher hemoglobin levels, especially in working memory and attention. Vitamin B12, folate, and vitamin D showed no significant associations with cognitive scores. Comparable trends were found across dementia subtypes. Conclusion Hemoglobin and homocysteine have been identified as important blood-based indicators of cognitive function, namely in the areas of executive, attention, and visuospatial skills, in elderly people with dementia and MCI. While vitamin B12, folate, and vitamin D seem less useful, their combination with MoCA Montreal Cognitive Assessment (MoCA) mild cognitive impairment (MCI) dementia subtypes homocysteine hemoglobin cognitive domains Full Text Additional Declarations No competing interests reported. Supplementary Files graphicalabstract.png 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-7409150","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":524379521,"identity":"70b9e67a-f8d4-4ddb-ba85-ff3dbf6319f2","order_by":0,"name":"Parmida Hajipour","email":"","orcid":"","institution":"Iran University of Medical Sciences","correspondingAuthor":false,"prefix":"","firstName":"Parmida","middleName":"","lastName":"Hajipour","suffix":""},{"id":524379522,"identity":"e60d91c3-5194-422a-b7da-32991390632b","order_by":1,"name":"Kiana Orangi","email":"","orcid":"","institution":"Iran University of Medical 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Impairment","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"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":"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":"Montreal Cognitive Assessment (MoCA), mild cognitive impairment (MCI), dementia subtypes, homocysteine, hemoglobin, cognitive domains","lastPublishedDoi":"10.21203/rs.3.rs-7409150/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7409150/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSerum biomarkers offer a non-invasive approach to support early cognitive assessment, but their association with cognitive function across dementia stages remains unclear. The Montreal Cognitive Assessment (MoCA) is a well-known screening tool, yet its reflection of underlying biochemical changes, particularly in specific cognitive domains, has been less explored.\u003c/p\u003e\u003ch2\u003eObjective\u003c/h2\u003e\u003cp\u003eThis study investigated the relationship between MoCA scores and plasma levels of homocysteine, hemoglobin, vitamin B12, folate, and vitamin D in individuals with mild cognitive impairment (MCI) or dementia, and whether these biomarkers explained domain-specific cognitive differences.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA retrospective cross-sectional study was conducted on 240 individuals aged\u0026thinsp;\u0026ge;\u0026thinsp;50 years with clinically diagnosed MCI or dementia. MoCA version 7.1 was administered, and biomarker levels were obtained from hospital records. Correlation and group comparison analyses were applied to assess associations between biomarker concentrations, MoCA performance, and dementia subtypes.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003ePoorer performance in the executive and visuospatial domains, such as clock drawing and serial subtraction, and lower MoCA scores were linked to elevated homocysteine levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.01). MoCA scores showed a positive correlation with higher hemoglobin levels, especially in working memory and attention. Vitamin B12, folate, and vitamin D showed no significant associations with cognitive scores. Comparable trends were found across dementia subtypes.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eHemoglobin and homocysteine have been identified as important blood-based indicators of cognitive function, namely in the areas of executive, attention, and visuospatial skills, in elderly people with dementia and MCI. While vitamin B12, folate, and vitamin D seem less useful, their combination with MoCA\u003c/p\u003e","manuscriptTitle":"Blood Biomarkers and MoCA Scores in MCI and Dementia: The Role of Homocysteine and Hemoglobin in Domain-Specific Cognitive Impairment","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-06 18:19:19","doi":"10.21203/rs.3.rs-7409150/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":"283ef8c6-0f97-4f8f-9d48-f0ac852c4e41","owner":[],"postedDate":"October 6th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-01-19T12:55:14+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-06 18:19:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7409150","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7409150","identity":"rs-7409150","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}