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Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study

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dc.contributor.author Tristão Pereira, Catarina
dc.contributor.author Fuster, Valentín
dc.contributor.author Oliva, Belén
dc.contributor.author Moreno Arciniegas, Andrea
dc.contributor.author García Lunar, Inés
dc.contributor.author Pérez Herreras, Cristina
dc.contributor.author Schöll, Michael
dc.contributor.author Suárez-Calvet, Marc
dc.contributor.author Moro, María Ángeles
dc.contributor.author García Álvarez, Ana
dc.contributor.author Fernández Ortiz, Antonio
dc.contributor.author Sánchez González, Javier
dc.contributor.author Zetterberg, Henrik
dc.contributor.author Blennow, Kaj
dc.contributor.author Ibáñez, Borja
dc.contributor.author Gispert López, Juan Domingo
dc.contributor.author Cortés Canteli, Marta
dc.date.accessioned 2024-05-27T06:20:49Z
dc.date.available 2024-05-27T06:20:49Z
dc.date.issued 2023
dc.identifier.citation Tristão-Pereira C, Fuster V, Oliva B, Moreno-Arciniegas A, Garcia-Lunar I, Perez-Herreras C, et al. Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study. Lancet Healthy Longev. 2023 Sep;4(9):e487-98. DOI: 10.1016/S2666-7568(23)00134-4
dc.identifier.issn 2666-7568
dc.identifier.uri http://hdl.handle.net/10230/60246
dc.description.abstract Background: Cardiovascular disease and dementia often coexist at advanced stages. Yet, longitudinal studies examining the interplay between atherosclerosis and its risk factors on brain health in midlife are scarce. We aimed to characterise the longitudinal associations between cerebral glucose metabolism, subclinical atherosclerosis, and cardiovascular risk factors in middle-aged asymptomatic individuals. Methods: The Progression of Early Subclinical Atherosclerosis (PESA) study is a Spanish longitudinal observational cohort study of 4184 asymptomatic individuals aged 40-54 years (NCT01410318). Participants with subclinical atherosclerosis underwent longitudinal cerebral [18F]fluorodeoxyglucose ([18F]FDG)-PET, and annual percentage change in [18F]FDG uptake was assessed (primary outcome). Cardiovascular risk was quantified with SCORE2 and subclinical atherosclerosis with three-dimensional vascular ultrasound (exposures). Multivariate regression and linear mixed effects models were used to assess associations between outcomes and exposures. Additionally, blood-based biomarkers of neuropathology were quantified and mediation analyses were performed. Secondary analyses were corrected for multiple comparisons using the false discovery rate (FDR) approach. Findings: This longitudinal study included a PESA subcohort of 370 participants (median age at baseline 49·8 years [IQR 46·1-52·2]; 309 [84%] men, 61 [16%] women; median follow-up 4·7 years [IQR 4·2-5·2]). Baseline scans took place between March 6, 2013, and Jan 21, 2015, and follow-up scans between Nov 24, 2017, and Aug 7, 2019. Persistent high risk of cardiovascular disease was associated with an accelerated decline of cortical [18F]FDG uptake compared with low risk (β=-0·008 [95% CI -0·013 to -0·002]; pFDR=0·040), with plasma neurofilament light chain, a marker of neurodegeneration, mediating this association by 20% (β=0·198 [0·008 to 0·740]; pFDR=0·050). Moreover, progression of subclinical carotid atherosclerosis was associated with an additional decline in [18F]FDG uptake in Alzheimer's disease brain regions, not explained by cardiovascular risk (β=-0·269 [95% CI -0·509 to -0·027]; p=0·029). Interpretation: Middle-aged asymptomatic individuals with persistent high risk of cardiovascular disease and subclinical carotid atherosclerosis already present brain metabolic decline, suggesting that maintenance of cardiovascular health during midlife could contribute to reductions in neurodegenerative disease burden later in life. Funding: Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, Santander Bank, Pro-CNIC Foundation, BrightFocus Foundation, BBVA Foundation, "la Caixa" Foundation.
dc.description.sponsorship We thank the PESA participants and the imaging, administrative, and medical PESA teams. The PESA study is equally co-funded by the Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC) and Santander Bank (Madrid, Spain) and also receives funding from the Instituto de Salud Carlos III (ISCIII), Madrid, Spain (PI15/02019), the European Regional Development Fund (ERDF—A Way to Build Europe), and the European Social Fund (ESF—Investing in Your Future). CNIC is a Severo Ochoa Center of Excellence (CEX2020-001041-S) and is supported by the ISCIII, the Spanish Ministry for Science and Innovation, and the Pro-CNIC Foundation. CT-P was supported by a “la Caixa” Foundation fellowship (ID 100010434, LCF/BQ/DI19/11730052). MC-C was supported by a Miguel Servet type II research contract (ISCIII, CPII21/00007) and the Fondo de Investigación Sanitaria (ISCIII, PI20/00819). We acknowledge the Sephardic Foundation on Aging and other donors of the Alzheimer's Disease Research (grant number A2022034S), a programme of the BrightFocus Foundation, for support of this research. This work was also partially produced with the support of a 2021 Leonardo Grant for Researchers and Cultural Creators from the BBVA Foundation awarded to MC-C (the Foundation takes no responsibility for the opinions, statements, and contents of this project, which are entirely the responsibility of its authors). BI was supported by the European Research Council (ERC-2018-CoG 819775-MATRIX). MS is supported by the Knut and Alice Wallenberg Foundation (Wallenberg Centre for Molecular and Translational Medicine; KAW2014.0363), the Swedish Research Council (2017-02869, 2021-02678, 2021-06545), the Swedish state under the agreement between the Swedish Government and the County Councils, the ALF-agreement (ALFGBG-813971, ALFGBG-965326), the Swedish Brain Foundation (FO2021-0311), and the Swedish Alzheimer Foundation (AF-740191). MS-C receives funding from the European Research Council (grant agreement number 948677), project “PI19/00155”, funded by ISCIII and co-funded by the EU, and a fellowship from “la Caixa” Foundation (ID 100010434) and from the EU's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 847648 (LCF/BQ/PR21/11840004). HZ is a Wallenberg Scholar supported by grants from the Swedish Research Council (#2022-01018), the EU's Horizon Europe research and innovation programme under grant agreement number 101053962, Swedish State Support for Clinical Research (#ALFGBG-71320), the Alzheimer Drug Discovery Foundation, USA (#201809-2016862), the AD Strategic Fund and the Alzheimer's Association (#ADSF-21-831376-C, #ADSF-21-831381-C, #ADSF-21-831377-C), the Bluefield Project, the Olav Thon Foundation, the Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (#FO2022-0270), the EU's Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement number 860197 (MIRIADE), the EU Joint Programme – Neurodegenerative Disease Research (JPND2021-00694), and the UK Dementia Research Institute at UCL (UKDRI-1003). KB is supported by the Swedish Research Council (#2017-00915, #2022-00732), the Swedish state under the agreement between the Swedish Government and the County Councils, the ALF-agreement (#ALFGBG-715986, #ALFGBG-965240), the Swedish Alzheimer Foundation (#AF-930351, #AF-939721, #AF-968270), Hjärnfonden, Sweden (#FO2017-0243, #ALZ2022-0006), the Alzheimer's Association 2021 Zenith Award (ZEN-21-848495), and the Alzheimer's Association 2022–2025 grant (SG-23-1038904 QC).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Lancet Healthy Longev. 2023 Sep;4(9):e487-98
dc.rights © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license (https://creativecommons.org/licenses/by-nc-nd/4.0).
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0
dc.subject.other Aterosclerosi
dc.subject.other Sistema cardiovascular--Malalties
dc.title Longitudinal interplay between subclinical atherosclerosis, cardiovascular risk factors, and cerebral glucose metabolism in midlife: results from the PESA prospective cohort study
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/S2666-7568(23)00134-4
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101053962
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/860197
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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