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dc.contributor.authorLow, Audrey
dc.contributor.authorPrats-Sedano, Maria A
dc.contributor.authorStefaniak, James D
dc.contributor.authorMcKiernan, Elizabeth Frances
dc.contributor.authorCarter, Stephen F
dc.contributor.authorDouvani, Maria-Eleni
dc.contributor.authorMak, Elijah
dc.contributor.authorSu, Li
dc.contributor.authorStupart, Olivia
dc.contributor.authorMuniz, Graciela
dc.contributor.authorRitchie, Karen
dc.contributor.authorRitchie, Craig W
dc.contributor.authorMarkus, Hugh
dc.contributor.authorO'Brien, John
dc.date.accessioned2022-01-14T00:30:10Z
dc.date.available2022-01-14T00:30:10Z
dc.date.issued2022-02-08
dc.identifier.issn0022-3050
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/332687
dc.description.abstractBACKGROUND: Markers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We investigated whether the Cardiovascular Risk Factors, Ageing and Dementia (CAIDE) risk score was associated with markers of cerebral small vessel disease (SVD), and if it predicted future progression of SVD. We also determined its relationship to systemic inflammation, which has been additionally implicated in dementia and SVD. METHODS: Cognitively healthy midlife participants were assessed at baseline (n=185) and 2-year follow-up (n=158). To assess SVD, we quantified white matter hyperintensities (WMH), enlarged perivascular spaces (EPVS), microbleeds and lacunes. We derived composite scores of SVD burden, and subtypes of hypertensive arteriopathy and cerebral amyloid angiopathy. Inflammation was quantified using serum C-reactive protein (CRP) and fibrinogen. RESULTS: At baseline, higher CAIDE scores were associated with all markers of SVD and inflammation. Longitudinally, CAIDE scores predicted greater total (p<0.001), periventricular (p<0.001) and deep (p=0.012) WMH progression, and increased CRP (p=0.017). Assessment of individual CAIDE components suggested that markers were driven by different risk factors (WMH/EPVS: age/hypertension, lacunes/deep microbleeds: hypertension/obesity). Interaction analyses demonstrated that higher CAIDE scores amplified the effect of age on SVD, and the effect of WMH on poorer memory. CONCLUSION: Higher CAIDE scores, indicating greater risk of dementia, predicts future progression of both WMH and systemic inflammation. Findings highlight the CAIDE score's potential as both a prognostic and predictive marker in the context of cerebrovascular disease, identifying at-risk individuals who might benefit most from managing modifiable risk.
dc.description.sponsorshipResearch grants from the UK Alzheimer's Society, the US Alzheimer’s Association and philanthropic donations. This work was funded by a grant for the PREVENT-Dementia programme from the UK Alzheimer’s Society (grant numbers 178 and 264), and the PREVENT-Dementia study is also supported by the US Alzheimer’s Association (grant number TriBEKa-17–519007) and philanthropic donations. AL is supported by the Lee Kuan Yew Fitzwilliam PhD Scholarship and the Tan Kah Kee Postgraduate Scholarship. JDS is a Wellcome clinical PhD fellow funded on grant 203914/Z/16/Z to the Universities of Manchester, Leeds, Newcastle and Sheffield. EM is supported by Alzheimer’s Society Junior Research Fellowship (RG 9611). LS is supported by the Cambridge NIHR Biomedical Research Centre (BRC) and Alzheimer’s Research UK (ARUK-SRF2017B-1). HSM is supported by an NIHR Senior Investigator award. JOB and HSM receive infrastructural support from the Cambridge NIHR Biomedical Research Centre (BRC). This research was supported by the NIHR Cambridge BRC (BRC-1215-20014). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care.
dc.publisherBMJ
dc.rightsAll Rights Reserved
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserved
dc.titleCAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study.
dc.typeArticle
dc.publisher.departmentDepartment of Psychiatry
dc.date.updated2022-01-06T18:10:27Z
prism.publicationNameJ Neurol Neurosurg Psychiatry
dc.identifier.doi10.17863/CAM.80131
dcterms.dateAccepted2021-12-27
rioxxterms.versionofrecord10.1136/jnnp-2021-327462
rioxxterms.versionAM
dc.contributor.orcidLow, Audrey [0000-0002-2520-454X]
dc.contributor.orcidMcKiernan, Elizabeth Frances [0000-0001-7076-8216]
dc.contributor.orcidMarkus, Hugh [0000-0002-9794-5996]
dc.contributor.orcidO'Brien, John [0000-0002-0837-5080]
dc.identifier.eissn1468-330X
rioxxterms.typeJournal Article/Review
cam.issuedOnline2022-02-08
cam.orpheus.successThu Feb 24 18:06:37 GMT 2022 - Embargo updated*
cam.orpheus.counter1
cam.depositDate2022-01-06
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2022-02-08


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