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Genetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSOUMARE, Aicha
dc.contributor.authorBIS, J. C.
dc.contributor.authorSURAKKA, I.
dc.contributor.authorJUERGENSON, T.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorJOLY, Pierre
dc.contributor.authorKNOL, M. J.
dc.contributor.authorWANG, R. Q.
dc.contributor.authorYANG, Q.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSATIZABAL, Claudia
dc.contributor.authorGUDJONSSON, A.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUTELOUP, Vincent
dc.contributor.authorPHUAH, C. L.
dc.contributor.authorVAN DUIJN, C. M.
dc.contributor.authorCRUCHAGA, C.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHENE, Genevieve
dc.contributor.authorLOPEZ, O. L.
dc.contributor.authorPSATY, B. M.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTZOURIO, Christophe
dc.contributor.authorAMOUYEL, P.
dc.contributor.authorADAMS, H. H.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorJACQMIN-GADDA, Helene
dc.contributor.authorIKRAM, M. A.
dc.contributor.authorGUDNASON, V.
dc.contributor.authorMILANI, L.
dc.contributor.authorWINSVOLD, B. S.
dc.contributor.authorHVEEM, K.
dc.contributor.authorMATTHEWS, P. M.
dc.contributor.authorLONGSTRETH, W. T.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSESHADRI, Sudha
dc.contributor.authorLAUNER, L. J.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2024-08-20T12:04:05Z
dc.date.available2024-08-20T12:04:05Z
dc.date.issued2024-05-01
dc.identifier.issn2574-3805en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/201197
dc.description.abstractEnImportance Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases. Design, Setting, and Participants This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was examined. Data analysis was performed from July 26, 2020, through July 24, 2022. Exposures Genetically determined WMH burden and BP levels, as well as genetic liability to stroke derived from genome-wide association studies (GWASs) in European ancestry populations. Main Outcomes and Measures The association of genetic instruments for WMH, stroke, and BP with dementia was studied using GWASs of AD (defined clinically and additionally meta-analyzed including both clinically diagnosed AD and AD defined based on parental history [AD-meta]) for 2SMR and incident all-cause dementia for longitudinal analyses. Results In 2SMR (summary statistics-based) analyses using AD GWASs with up to 75 024 AD cases (mean [SD] age at AD onset, 75.5 [4.4] years; 56.9% women), larger WMH burden showed evidence for a causal association with increased risk of AD (odds ratio [OR], 1.43; 95% CI, 1.10-1.86; P = .007, per unit increase in WMH risk alleles) and AD-meta (OR, 1.19; 95% CI, 1.06-1.34; P = .008), after accounting for pulse pressure for the former. Blood pressure traits showed evidence for a protective association with AD, with evidence for confounding by shared genetic instruments. In the longitudinal (individual-level data) analyses involving 10 699 incident all-cause dementia cases (mean [SD] age at dementia diagnosis, 74.4 [9.1] years; 55.4% women), no significant association was observed between larger WMH burden and incident all-cause dementia (hazard ratio [HR], 1.02; 95% CI, 1.00-1.04; P = .07). Although all exposures were associated with mortality, with the strongest association observed for systolic BP (HR, 1.04; 95% CI, 1.03-1.06; P = 1.9 x 10-14), there was no evidence for selective survival bias during follow-up using illness-death models. In secondary analyses using polygenic scores, the association of genetic liability to stroke, but not genetically determined WMH, with dementia outcomes was attenuated after adjusting for interim stroke. Conclusions These findings suggest that WMH is a primary vascular factor associated with dementia risk, emphasizing its significance in preventive strategies for dementia. Future studies are warranted to examine whether this finding can be generalized to non-European populations.
dc.description.sponsorshipStopping cognitive decline and dementia by fighting covert cerebral small vessel diseaseen_US
dc.description.sponsorshipVaincre les maladies vasculaires cérébrales par un nouveau paradigme de prévention de précision et d'innovation thérapeutiqueen_US
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enGenetic Complexities of Cerebral Small Vessel Disease, Blood Pressure, and Dementia
dc.title.alternativeJAMA Netw Openen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1001/jamanetworkopen.2024.12824en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed38776079en_US
bordeaux.journalJAMA Network Openen_US
bordeaux.pagee2412824en_US
bordeaux.volume7en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue5en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.teamBIOSTAT_BPHen_US
bordeaux.teamHEALTHY_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDNational Heart, Lung, and Blood Instituteen_US
bordeaux.identifier.funderIDFondation Plan Alzheimeren_US
bordeaux.identifier.funderIDSanofien_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDMutuelle Générale de l'Education Nationaleen_US
hal.identifierhal-04673646
hal.version1
hal.date.transferred2024-08-20T12:04:11Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
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