Afficher la notice abrégée

Polygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification

dc.rights.licenseopenen_US
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorD'AOUST, Tim
dc.contributor.authorCLOCCHIATTI-TUOZZO, Santiago
dc.contributor.authorRIVIER, Cyprien A
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorMISHRA, Aniket
dc.contributor.authorHACHIYA, Tsuyoshi
dc.contributor.authorGRENIER-BOLEY, Benjamin
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSOUMARE, Aicha
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUPERRON, Marie-Gabrielle
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorLE GRAND, Quentin
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorBOUTELOUP, Vincent
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorPROUST LIMA, Cecile
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorSAMIERI, Cecilia
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorNEUFFER, Jeanne
dc.contributor.authorSARGURUPREMRAJ, Muralidharan
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorCHENE, Genevieve
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorHELMER, Catherine
dc.contributor.authorTHIBAULT, Mura
dc.contributor.authorAMOUYEL, Philippe
dc.contributor.authorLAMBERT, Jean-Charles
dc.contributor.authorKAMATANI, Yoichiro
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorJACQMIN-GADDA, Helene
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorTREGOUET, David-Alexandre
dc.contributor.authorINOUYE, Michael
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDUFOUIL, Carole
dc.contributor.authorFALCONE, Guido J
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorDEBETTE, Stephanie
dc.date.accessioned2025-04-24T12:05:24Z
dc.date.available2025-04-24T10:02:01Z
dc.date.available2025-04-24T12:05:24Z
dc.date.issued2025-03-01
dc.identifier.issn1552-5279en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/206397.2
dc.description.abstractEnINTRODUCTION: An integrative polygenic risk score (iPRS) capturing the neurodegenerative and vascular contribution to dementia could identify high-risk individuals and improve risk prediction. METHODS: We developed an iPRS for dementia (iPRS-DEM) in Europeans (aged 65+), comprising genetic risk for Alzheimer's disease (AD) and 23 vascular or neurodegenerative traits (excluding apolipoprotein E [APOE]). iPRS-DEM was evaluated across cohorts comprising older community-dwelling people (N = 3702), a multi-ancestry biobank (N = 130,797 Europeans; 105,404 non-Europeans), and dementia-free memory clinic participants (N = 2032). RESULTS: iPRS-DEM was associated with dementia risk independently of APOE in the elderly (subdistribution hazard ratio [sHR](per1SD )= 1.15, 95% confidence interval [CI]: 1.03 to 1.28), which generalized to Europeans (EUR-sHR(per1SD )= 1.28, 95% CI: 1.09 to 1.51]), East-Asians (EAS-sHR(per1SD )= 5.29, 95% CI: 1.43 to 34.36), and memory-clinic participants (sHR(per1SD )= 1.25, 95% CI: 1.11 to 1.42). Prediction was comparable to clinical risk factors in older community-dwelling people, with improved performance among memory-clinic patients. Risk stratification was enhanced by defining four genetic risk groups with iPRS-DEM and APOE epsilon 4, reaching five-fold increased risk in APOE epsilon 4+/iPRS-DEM+ memory-clinic participants. DISCUSSION: Alongside APOE epsilon 4, iPRS-DEM may refine risk stratification for the enrichment of dementia clinical trials and prevention programs. Highlights iPRS-DEM reflects neurodegenerative and vascular contribution to dementia. We show iPRS-DEM captures additional dementia genetic risk beyond APOE and AD-PRS. iPRS-DEM, in combination with APOE epsilon 4, shows promise for dementia risk stratification. Our results generalize across both population-based and memory-clinic settings. We show transportability of iPRS-DEM to East Asian ancestry.
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.description.sponsorshipUniversity of Bordeaux Graduate School in Digital Public Healthen_US
dc.language.isoENen_US
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/*
dc.subject.enApolipoprotein E Genotype
dc.subject.enCommunity‐Dwelling Elderly
dc.subject.enCompeting Risk Analysis
dc.subject.enDementia Prevention
dc.subject.enIncident Dementia
dc.subject.enLongitudinal Study
dc.subject.enMemory Clinic
dc.subject.enMulti‐Ancestry Biobank
dc.subject.enPolygenic Risk Score
dc.subject.enTransportability Of PRS
dc.subject.enVascular Cognitive Impairment
dc.title.enPolygenic score integrating neurodegenerative and vascular risk informs dementia risk stratification
dc.title.alternativeAlzheimers Dementen_US
dc.typeArticle de revueen_US
dc.identifier.doi10.1002/alz.70014en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed40042447en_US
bordeaux.journalAlzheimer's & Dementia : the Journal of the Alzheimer's Associationen_US
bordeaux.pagee70014en_US
bordeaux.volume21en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue3en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamBIOSTAT_BPHen_US
bordeaux.teamELEANOR_BPHen_US
bordeaux.teamLEHA_BPHen_US
bordeaux.teamPHARES_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDFondation Claude Pompidouen_US
bordeaux.identifier.funderIDMutuelle Générale de l'Education Nationaleen_US
bordeaux.identifier.funderIDFondation Plan Alzheimeren_US
bordeaux.identifier.funderIDFondation pour la Recherche Médicaleen_US
bordeaux.identifier.funderIDConseil Régional Aquitaineen_US
bordeaux.identifier.funderIDFondation de Franceen_US
bordeaux.identifier.funderIDNational Institutes of Healthen_US
hal.identifierhal-05045641
hal.version1
hal.date.transferred2025-04-24T12:05:35Z
hal.popularnonen_US
hal.audienceInternationaleen_US
hal.exporttrue
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Alzheimer's%20&%20Dementia%20:%20the%20Journal%20of%20the%20Alzheimer's%20Association&rft.date=2025-03-01&rft.volume=21&rft.issue=3&rft.spage=e70014&rft.epage=e70014&rft.eissn=1552-5279&rft.issn=1552-5279&rft.au=D'AOUST,%20Tim&CLOCCHIATTI-TUOZZO,%20Santiago&RIVIER,%20Cyprien%20A&MISHRA,%20Aniket&HACHIYA,%20Tsuyoshi&rft.genre=article


Fichier(s) constituant ce document

Thumbnail
Nom:
BPH_AD_2025_DAoust(2).pdf
Taille:
3.061Mo
Format:
PDF
Voir/Ouvrir
Thumbnail
Nom:
BPH_AD_2025_DAoust.pdf
Taille:
3.061Mo
Format:
Inconnu
Voir/Ouvrir
Thumbnail
Nom:
license_rdf
Taille:
811octets
Format:
application/rdf+xml
Voir/Ouvrir

Ce document figure dans la(les) collection(s) suivante(s)

Afficher la notice abrégée

Historique des versions

VersionItemDateEn bref
220.500.12278/206397.2*2025-04-24T11:52:58Zexport hal impossible
120.500.12278/2063972025-04-24T10:02:01Z

*Version sélectionnée