Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI Study

Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI 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 Research Article Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI Study Wenxia Yang, Liang Zhou, Hao Li, SiRu Kang, Jiahao Yan, Lili Xu, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8461179/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: Neurovascular coupling (NVC) impairment is implicated in mild cognitive impairment (MCI). Cognitive reserve (CR) may protect against neurodegeneration, but its relationship with NVC in MCI remains unclear. Objective: This study aimed to investigate whether CR modulates NVC and its association with cognition in MCI patients. Materials and Methods: The study enrolled 113 MCI patients and 83 healthy controls (HCs). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) scanning to calculate the ratios of CBF to neural activity metrics (ALFF, fALFF, ReHo, DC) as measures of NVC. They also completed a battery of neuropsychological tests and the Cognitive Reserve Index Questionnaire (CRIq). Results: Compared to HCs, MCI patients showed widespread reduction in whole-brain gray matter NVC. Voxel-wise analysis revealed significantly decreased NVC ratios in cognitive-related brain regions such as the frontal and temporal lobes, while ratios were increased in visual and subcortical areas including the lingual gyrus and putamen. Correlation analysis indicated a positive correlation between the CBF/fALFF ratio in the right lingual gyrus and CRIq scores, whereas NVC ratios in the right orbital frontal gyrus and right middle frontal gyrus were negatively correlated with CRIq. Mediation analysis further demonstrated that the NVC ratios in these specific brain regions mediated the relationship between total CRIq scores and cognitive performance (as measured by MoCA, MMSE, and AVLT-Rec scores). Conclusion: CR is associated with altered NVC in MCI, suggesting a potential neuroprotective mechanism and target for early intervention. Neurovascular coupling，Mild cognitive impairment，Cognitive reserve，Cognitive function，Mediation analysis Full Text Additional Declarations No competing interests reported. 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-8461179","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":578967133,"identity":"756ef3de-0725-495e-be86-ed010836d9ba","order_by":0,"name":"Wenxia Yang","email":"","orcid":"","institution":"Department of Magnetic Resonance, The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Wenxia","middleName":"","lastName":"Yang","suffix":""},{"id":578967135,"identity":"0c524f84-c241-4e8e-ae04-b076fa195d47","order_by":1,"name":"Liang Zhou","email":"","orcid":"","institution":"Jingzhou Hospital Affiliated to Yangtze University","correspondingAuthor":false,"prefix":"","firstName":"Liang","middleName":"","lastName":"Zhou","suffix":""},{"id":578967137,"identity":"b1cd7c54-4b1b-47e6-a352-a8a35289e244","order_by":2,"name":"Hao Li","email":"","orcid":"","institution":"Department of Magnetic Resonance, The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"Hao","middleName":"","lastName":"Li","suffix":""},{"id":578967140,"identity":"3d89d20f-4811-4e78-a991-3a5e264f6fd6","order_by":3,"name":"SiRu Kang","email":"","orcid":"","institution":"Department of Magnetic Resonance, The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":false,"prefix":"","firstName":"SiRu","middleName":"","lastName":"Kang","suffix":""},{"id":578967142,"identity":"3a97b965-749d-4a0a-81ae-8756dfa3b830","order_by":4,"name":"Jiahao 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Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABDElEQVRIiWNgGAWjYLACxgYQeRBIVliABSRI0HJGgiQtIEYbEVr4pc8YMP7cYZcn73i47eHXeRL2BgeYD97mYbDLw6VFsi/HgEHyTHKx4YGD7cay2ySYDQ6wJVvzMCQX49JicIbHgMGwjTlxY8PBNmnJbRJsBgd4zKR5GA4kNuDQYg/SkthWD9UyR4LH4AD/N7xaDHiAWg62HU6cDyQlPzZISABtYcOrReIMWwFjY9vxxA1ALdIMxyQMJA+zGVvOMUjGqYW/h3kD48+26sT5M44/k/xRY2PPd7z54Y03FXY4tTAwcJj/ALvwxgEGZh4QixnMxakeCNgfgCn5/gYGxh/4FI6CUTAKRsGIBQAu8FVgMfUoMAAAAABJRU5ErkJggg==","orcid":"","institution":"Department of Magnetic Resonance, The Second Hospital \u0026 Clinical Medical School, Lanzhou University","correspondingAuthor":true,"prefix":"","firstName":"Jing","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-12-27 12:53:30","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8461179/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8461179/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":104418186,"identity":"2d4f226e-c49d-4679-82dc-09e3c1b7a243","added_by":"auto","created_at":"2026-03-11 13:22:40","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1729476,"visible":true,"origin":"","legend":"","description":"","filename":"revisedmanuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8461179/v1_covered_86c555dc-ccbd-4cff-8efb-18493e1f2bcd.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI Study","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":"Neurovascular coupling，Mild cognitive impairment，Cognitive reserve，Cognitive function，Mediation analysis","lastPublishedDoi":"10.21203/rs.3.rs-8461179/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8461179/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e Neurovascular coupling (NVC) impairment is implicated in mild cognitive impairment (MCI). Cognitive reserve (CR) may protect against neurodegeneration, but its relationship with NVC in MCI remains unclear.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjective:\u003c/strong\u003e This study aimed to investigate whether CR modulates NVC and its association with cognition in MCI patients.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMaterials and Methods:\u003c/strong\u003e The study enrolled 113 MCI patients and 83 healthy controls (HCs). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and arterial spin labeling (ASL) scanning to calculate the ratios of CBF to neural activity metrics (ALFF, fALFF, ReHo, DC) as measures of NVC. They also completed a battery of neuropsychological tests and the Cognitive Reserve Index Questionnaire (CRIq).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Compared to HCs, MCI patients showed widespread reduction in whole-brain gray matter NVC. Voxel-wise analysis revealed significantly decreased NVC ratios in cognitive-related brain regions such as the frontal and temporal lobes, while ratios were increased in visual and subcortical areas including the lingual gyrus and putamen. Correlation analysis indicated a positive correlation between the CBF/fALFF ratio in the right lingual gyrus and CRIq scores, whereas NVC ratios in the right orbital frontal gyrus and right middle frontal gyrus were negatively correlated with CRIq. Mediation analysis further demonstrated that the NVC ratios in these specific brain regions mediated the relationship between total CRIq scores and cognitive performance (as measured by MoCA, MMSE, and AVLT-Rec scores).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion: \u003c/strong\u003eCR is associated with altered NVC in MCI, suggesting a potential neuroprotective mechanism and target for early intervention.\u003c/p\u003e","manuscriptTitle":"Neurovascular Coupling Mediates the Protective Effects of Cognitive Reserve in Mild Cognitive Impairment: A Multimodal MRI Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-26 17:26:53","doi":"10.21203/rs.3.rs-8461179/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":"2989d126-4e05-429b-9502-e3ca12a09509","owner":[],"postedDate":"January 26th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-03-11T13:09:28+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-26 17:26:53","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8461179","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8461179","identity":"rs-8461179","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}