Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population

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• dc.contributor.author Padrela, Beatriz E.
• dc.contributor.author Lorenzini, Luigi
• dc.contributor.author Collij, Lyduine E.
• dc.contributor.author Vállez García, David
• dc.contributor.author Coomans, Emma
• dc.contributor.author Ingala, Silvia
• dc.contributor.author Tomassen, Jori
• dc.contributor.author Deckers, Quinten
• dc.contributor.author Shekari, Mahnaz
• dc.contributor.author de Geus, Eco
• dc.contributor.author van de Giessen, Elsmarieke
• dc.contributor.author Ten Kate, Mara
• dc.contributor.author Visser, Pieter Jelle
• dc.contributor.author Barkhof, Frederik
• dc.contributor.author Petr, Jan
• dc.contributor.author den Braber, Anouk
• dc.contributor.author Mutsaerts, Henk
• dc.date.accessioned 2024-03-11T07:13:56Z
• dc.date.available 2024-03-11T07:13:56Z
• dc.date.issued 2023
• dc.description.abstract Aging-related cognitive decline can be accelerated by a combination of genetic factors, cardiovascular and cerebrovascular dysfunction, and amyloid-β burden. Whereas cerebral blood flow (CBF) has been studied as a potential early biomarker of cognitive decline, its normal variability in healthy elderly is less known. In this study, we investigated the contribution of genetic, vascular, and amyloid-β components of CBF in a cognitively unimpaired (CU) population of monozygotic older twins. We included 134 participants who underwent arterial spin labeling (ASL) MRI and [18F]flutemetamol amyloid-PET imaging at baseline and after a four-year follow-up. Generalized estimating equations were used to investigate the associations of amyloid burden and white matter hyperintensities with CBF. We showed that, in CU individuals, CBF: 1) has a genetic component, as within-pair similarities in CBF values were moderate and significant (ICC > 0.40); 2) is negatively associated with cerebrovascular damage; and 3) is positively associated with the interaction between cardiovascular risk scores and early amyloid-β burden, which may reflect a vascular compensatory response of CBF to early amyloid-β accumulation. These findings encourage future studies to account for multiple interactions with CBF in disease trajectory analyses.
• dc.description.sponsorship The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The project leading to this article has received funding from the EU Joint Program for Neurodegenerative Disease Research, provided by the Netherlands Organisation for Health Research and Development and Alzheimer Nederland (DEBBIE JPND2020-568-106), and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 115952. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. This communication reflects the views of the authors, and neither the Innovative Medicines Initiative nor the European Union or EFPIA are liable for any use of the information contained herein. This work has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking EMIF grant agreement n°115372 and Stichting Dioraphte. This work also received in-kind sponsoring of the PET tracer from GE Healthcare. MK is supported by Alzheimer Nederland (WE.03-2021-16). PV receives research support from Bristol-Myers Squibb, EU/EFPIA Innovative Medicines Initiative Joint Undertaking, and EU Joint Programme – Neurodegenerative Disease Research (JPND and ZonMw). FB is supported by the NIHR UCLH Biomedical Research Centre (BRC) and receives research support via grants from EU/EFPIA Innovative Medicines Initiative Joint Undertaking (AMYPAD consortium), and EuroPOND (H2020). HM is supported by the Dutch Heart Foundation (03-004-2020-T049) and by the Eurostars-2 joint programme with co-funding from the European Union Horizon 2020 research and innovation programme (ASPIRE E!113701), provided by the Netherlands Enterprise Agency (RvO).
• dc.format.mimetype application/pdf
• dc.identifier.citation Padrela BE, Lorenzini L, Collij LE, García DV, Coomans E, Ingala S, Tomassen J, Deckers Q, Shekari M, Geus EJ, van de Giessen E, Ten Kate M, Visser PJ, Barkhof F, Petr J, den Braber A, Mutsaerts HJ. Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population. J Cereb Blood Flow Metab. 2023 Oct;43(10):1726-36. DOI: 10.1177/0271678X231178993
• dc.identifier.doi http://dx.doi.org/10.1177/0271678X231178993
• dc.identifier.issn 0271-678X
• dc.identifier.uri http://hdl.handle.net/10230/59365
• dc.language.iso eng
• dc.publisher SAGE Publications
• dc.relation.ispartof J Cereb Blood Flow Metab. 2023 Oct;43(10):1726-36
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
• dc.rights © The Author(s) 2023. This article is distributed under the terms of the Creative Commons Attribution 4.0 License (https://creativecommons.org/licenses/by/4.0/) which permits any use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Alzheimer’s disease
• dc.subject.keyword Arterial spin labeling (ASL)
• dc.subject.keyword Cerebral blood flow (CBF)
• dc.subject.keyword Twin analysis
• dc.subject.keyword White matter hyperintensities
• dc.title Genetic, vascular and amyloid components of cerebral blood flow in a preclinical population
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion