dc.contributor.author | Cumplido-Mayoral, Irene | |
dc.contributor.author | Brugulat-Serrat, Anna | |
dc.contributor.author | Sánchez-Benavides, Gonzalo | |
dc.contributor.author | González-Escalante, Armand | |
dc.contributor.author | Anastasi, Federica | |
dc.contributor.author | Milà-Alomà, Marta | |
dc.contributor.author | López-Martos, David | |
dc.contributor.author | Akinci, Muge | |
dc.contributor.author | Falcón, Carles | |
dc.contributor.author | Shekari, Mahnaz | |
dc.contributor.author | Cacciaglia, Raffaele | |
dc.contributor.author | Arenaza-Urquijo, Eider M | |
dc.contributor.author | Minguillón, Carolina | |
dc.contributor.author | Fauria, Karine | |
dc.contributor.author | Molinuevo, José Luis | |
dc.contributor.author | Suárez-Calvet, Marc | |
dc.contributor.author | Grau-Rivera, Oriol | |
dc.contributor.author | Vilaplana, Verónica | |
dc.contributor.author | Gispert, Juan Domingo | |
dc.date.accessioned | 2024-07-03T08:34:10Z | |
dc.date.available | 2024-07-03T08:34:10Z | |
dc.date.issued | 2024-04 | |
dc.identifier.citation | Lancet Healthy Longev. 2024 Apr;5(4):e276-e286. | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/19925 | |
dc.description.abstract | BACKGROUND
Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer's disease pathology. We also explored whether the mediation effect is specific to cognitive domain.
METHODS
In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3·28 (SD 0·27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer's cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer's disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals.
FINDINGS
Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15·73% [95% CI 14·22-16·66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28·03% [26·25-29·21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3·52% [0·072-4·17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group.
INTERPRETATION
Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline.
FUNDING
La Caixa Foundation, the TriBEKa Imaging Platform, and the Universities and Research Secretariat of the Catalan Government.
TRANSLATION
For the Spanish translation of the abstract see Supplementary Materials section. | es_ES |
dc.description.sponsorship | This publication is part of the ALFA study. We thank the ALFA project
participants and relatives, without whom this research would not have
been possible. We thank Kaj Blennow and Henrik Zetterberg for
performing the measurements of cerebrospinal fluid Aβ42:Aβ40 ratio.
We thank Roche Diagnostics International for providing the kits to
measure cerebrospinal fluid biomarkers. The Roche NeuroToolKit is
a panel of exploratory prototype assays designed to evaluate biomarkers
associated with key pathological events characteristic of Alzheimer’s
disease and other neurological disorders, used for research purposes only
and not approved for clinical use. COBAS and ELECSYS are trademarks
of Roche. All other product names and trademarks are the property of
their respective owners. The ALFA+ study receives funding from La Caixa
Foundation (100010434; LCF/PR/GN17/50300004) and the Alzheimer’s
Association and an international anonymous charity foundation through
the TriBEKa Imaging Platform project (TriBEKa 17 519007). Additional
support has been received from the Universities and Research Secretariat,
Ministry of Business and Knowledge of the Catalan Government (2021
SGR 009132017-SGR-892). MS-C receives funding from the European
Research Council under the EU Horizon 2020 research and innovation
programme (948677; project PI19/00155), funded by Instituto de Salud
Carlos III and co-funded by the EU, and from a fellowship from La Caixa
Foundation (100010434) and from the EU Horizon 2020 research and
innovation programme under the Marie Skłodowska-Curie grant (847648;
LCF/BQ/PR21/11840004). DL-M is supported by Instituto de
Salud Carlos III (PI19/00117; co-funded by European Regional
Development Fund, European Social Fund A Way to Make Europe, and
Investing in your Future). EMA-U is supported by the Spanish Ministry of
Science and Innovation State Research Agency (RYC2018-026053-I), cofunded by the European Social Fund and the Spanish Ministry of Science
and Innovation (PID2019-111514RA-I00). VV has been supported by the
Spanish Research Agency (PID2020-116907RB-I00 of the call MCIN/
AEI/10.13039/501100011033). JDG is supported by the Spanish Ministry of
Science and Innovation (RYC-2013-13054). JDG has also received research
support from the EU and European Federation of Pharmaceutical
Industries and Associations Innovative Medicines Initiative Joint
Undertaking AMYPAD (115952), European Institute of Innovation and
Technology Digital (2021), and from Ministerio de Ciencia y
Universidades (RTI2018-102261). GS-B receives funding from the
Ministerio de Ciencia e Innovacion, Spanish Research Agency (PID2020-
119556RA-I00). OG-R receives funding from the Alzheimer’s Association
Research Fellowship (2019-AARF-644568), from Instituto de Salud Carlos
III (PI19/00117), and from the Spanish Ministry of Science, Innovation
and Universities (Juan de la Cierva programme IJC2020-043417-I). | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | Elsevier | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by-nc-nd/4.0/ | * |
dc.subject.mesh | Alzheimer Disease | es_ES |
dc.subject.mesh | Cognitive Dysfunction | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Middle Aged | es_ES |
dc.subject.mesh | Aged | es_ES |
dc.subject.mesh | Cohort Studies | es_ES |
dc.subject.mesh | Longitudinal Studies | es_ES |
dc.subject.mesh | Positron-Emission Tomography | es_ES |
dc.subject.mesh | Neuropsychological Tests | es_ES |
dc.subject.mesh | Neuroimaging | es_ES |
dc.subject.mesh | Brain | es_ES |
dc.subject.mesh | Risk Factors | es_ES |
dc.title | The mediating role of neuroimaging-derived biological brain age in the association between risk factors for dementia and cognitive decline in middle-aged and older individuals without cognitive impairment: a cohort study. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Attribution-NonCommercial-NoDerivatives 4.0 Internacional | * |
dc.identifier.pubmedID | 38555920 | es_ES |
dc.format.volume | 5 | es_ES |
dc.format.number | 4 | es_ES |
dc.format.page | e276 | es_ES |
dc.identifier.doi | 10.1016/S2666-7568(24)00025-4 | es_ES |
dc.contributor.funder | Fundación La Caixa | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. European Research Council (ERC) | es_ES |
dc.contributor.funder | Unión Europea. Comisión Europea. H2020 | es_ES |
dc.contributor.funder | Instituto de Salud Carlos III | es_ES |
dc.contributor.funder | Marie Curie | es_ES |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | es_ES |
dc.contributor.funder | Ministerio de Ciencia y Universidades (España) | es_ES |
dc.contributor.funder | Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 2666-7568 | es_ES |
dc.relation.publisherversion | 10.1016/S2666-7568(24)00025-4 | es_ES |
dc.identifier.journal | The lancet. Healthy longevity | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/ERC/948677 | es_ES |
dc.relation.projectID | info:eu-repo/grantAgreement/EC/H2020/847648 | es_ES |
dc.rights.accessRights | open access | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/100010434 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LCF/PR/GN17/50300004 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/SGR/009132017-SGR-892 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI19/00155 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/LCF/BQ/PR21/11840004 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RYC2018-026053-I | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2019-111514RA-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2020-116907RB-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/MCIN/AEI/10.13039/501100011033 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RYC-2013-13054 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/RTI2018-102261 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PID2020-119556RA-I00 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/PI19/00117 | es_ES |
dc.relation.projectFECYT | info:eu-repo/grantAgreement/ES/IJC2020-043417-I | es_ES |