Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention
Background: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disord...
| Autores: | , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2024 |
| País: | España |
| Institución: | Universitat Pompeu Fabra |
| Repositorio: | Repositorio Digital de la UPF |
| OAI Identifier: | oai:repositori.upf.edu:10230/60769 |
| Acceso en línea: | http://hdl.handle.net/10230/60769 http://dx.doi.org/10.1186/s12937-024-00966-w |
| Access Level: | acceso abierto |
| Palabra clave: | 2-AG Cognition Endocannabinoids Mediterranean diet Metabolic syndrome Sex differences |
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Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| title |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| spellingShingle |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention Soldevila-Domenech, Natalia 2-AG Cognition Endocannabinoids Mediterranean diet Metabolic syndrome Sex differences |
| title_short |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| title_full |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| title_fullStr |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| title_full_unstemmed |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| title_sort |
Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet intervention |
| dc.creator.none.fl_str_mv |
Soldevila-Domenech, Natalia Fagundo, Beatriz Cuenca Royo, Aida Ma, 1981- Forcano, Laura Gomis González, Maria, 1988- Boronat Rigol, Anna, 1990- Pastor, Antonio Castañer, Olga Zomeño Fajardo, María Dolores Goday Arnó, Albert Dierssen, Mara Baghizadeh Hosseini, Khashayar Ros, Emilio Corella, Dolores Martínez-González, Miguel Ángel, 1957- Salas Salvadó, Jordi Fernández Aranda, Fernando Fitó Colomer, Montserrat Torre Fornell, Rafael de la |
| author |
Soldevila-Domenech, Natalia |
| author_facet |
Soldevila-Domenech, Natalia Fagundo, Beatriz Cuenca Royo, Aida Ma, 1981- Forcano, Laura Gomis González, Maria, 1988- Boronat Rigol, Anna, 1990- Pastor, Antonio Castañer, Olga Zomeño Fajardo, María Dolores Goday Arnó, Albert Dierssen, Mara Baghizadeh Hosseini, Khashayar Ros, Emilio Corella, Dolores Martínez-González, Miguel Ángel, 1957- Salas Salvadó, Jordi Fernández Aranda, Fernando Fitó Colomer, Montserrat Torre Fornell, Rafael de la |
| author_role |
author |
| author2 |
Fagundo, Beatriz Cuenca Royo, Aida Ma, 1981- Forcano, Laura Gomis González, Maria, 1988- Boronat Rigol, Anna, 1990- Pastor, Antonio Castañer, Olga Zomeño Fajardo, María Dolores Goday Arnó, Albert Dierssen, Mara Baghizadeh Hosseini, Khashayar Ros, Emilio Corella, Dolores Martínez-González, Miguel Ángel, 1957- Salas Salvadó, Jordi Fernández Aranda, Fernando Fitó Colomer, Montserrat Torre Fornell, Rafael de la |
| author2_role |
author author author author author author author author author author author author author author author author author author |
| dc.subject.none.fl_str_mv |
2-AG Cognition Endocannabinoids Mediterranean diet Metabolic syndrome Sex differences |
| topic |
2-AG Cognition Endocannabinoids Mediterranean diet Metabolic syndrome Sex differences |
| description |
Background: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration: ISRCTN89898870. |
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2024 |
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2024 2024 2024 |
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info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10230/60769 http://dx.doi.org/10.1186/s12937-024-00966-w |
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http://hdl.handle.net/10230/60769 http://dx.doi.org/10.1186/s12937-024-00966-w |
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Inglés |
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Inglés |
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Nutr J. 2024 Jun 12;23(1):61 info:eu-repo/grantAgreement/EC/H2020/340918 info:eu-repo/grantAgreement/EC/H2020/728018 info:eu-repo/grantAgreement/EC/H2020/847879 |
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openAccess |
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BioMed Central |
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BioMed Central |
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reponame:Repositorio Digital de la UPF instname:Universitat Pompeu Fabra |
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Universitat Pompeu Fabra |
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Repositorio Digital de la UPF |
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Relationship between sex, APOE genotype, endocannabinoids and cognitive change in older adults with metabolic syndrome during a 3-year Mediterranean diet interventionSoldevila-Domenech, NataliaFagundo, BeatrizCuenca Royo, Aida Ma, 1981-Forcano, LauraGomis González, Maria, 1988-Boronat Rigol, Anna, 1990-Pastor, AntonioCastañer, OlgaZomeño Fajardo, María DoloresGoday Arnó, AlbertDierssen, MaraBaghizadeh Hosseini, KhashayarRos, EmilioCorella, DoloresMartínez-González, Miguel Ángel, 1957-Salas Salvadó, JordiFernández Aranda, FernandoFitó Colomer, MontserratTorre Fornell, Rafael de la2-AGCognitionEndocannabinoidsMediterranean dietMetabolic syndromeSex differencesBackground: The Mediterranean diet (MedDiet) has demonstrated efficacy in preventing age-related cognitive decline and modulating plasma concentrations of endocannabinoids (eCBs) and N-acylethanolamines (NAEs, or eCB-like compounds), which are lipid mediators involved in multiple neurological disorders and metabolic processes. Hypothesizing that eCBs and NAEs will be biomarkers of a MedDiet intervention and will be related to the cognitive response, we investigated this relationship according to sex and apolipoprotein E (APOE) genotype, which may affect eCBs and cognitive performance. Methods: This was a prospective cohort study of 102 participants (53.9% women, 18.8% APOE-ɛ4 carriers, aged 65.6 ± 4.5 years) from the PREDIMED-Plus-Cognition substudy, who were recruited at the Hospital del Mar Research Institute (Barcelona). All of them presented metabolic syndrome plus overweight/obesity (inclusion criteria of the PREDIMED-Plus) and normal cognitive performance at baseline (inclusion criteria of this substudy). A comprehensive battery of neuropsychological tests was administered at baseline and after 1 and 3 years. Plasma concentrations of eCBs and NAEs, including 2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and N-docosahexaenoylethanolamine (DHEA), were also monitored. Baseline cognition, cognitive changes, and the association between eCBs/NAEs and cognition were evaluated according to gender (crude models), sex (adjusted models), and APOE genotype. Results: At baseline, men had better executive function and global cognition than women (the effect size of gender differences was - 0.49, p = 0.015; and - 0.42, p = 0.036); however, these differences became nonsignificant in models of sex differences. After 3 years of MedDiet intervention, participants exhibited modest improvements in memory and global cognition. However, greater memory changes were observed in men than in women (Cohen's d of 0.40 vs. 0.25; p = 0.017). In men and APOE-ε4 carriers, 2-AG concentrations were inversely associated with baseline cognition and cognitive changes, while in women, cognitive changes were positively linked to changes in DHEA and the DHEA/AEA ratio. In men, changes in the OEA/AEA and OEA/PEA ratios were positively associated with cognitive changes. Conclusions: The MedDiet improved participants' cognitive performance but the effect size was small and negatively influenced by female sex. Changes in 2-AG, DHEA, the OEA/AEA, the OEA/PEA and the DHEA/AEA ratios were associated with cognitive changes in a sex- and APOE-dependent fashion. These results support the modulation of the endocannabinoid system as a potential therapeutic approach to prevent cognitive decline in at-risk populations. Trial registration: ISRCTN89898870.Study resulting from the following grants: SLT006/17/00246, SLT002/16/00045 and SLT006/17/00077 funded by the Department of Health of the Generalitat de Catalunya by the calls “Acció instrumental de programes de recerca orientats en l’àmbit de la recerca i la innovació en salut” and “Pla estratègic de recerca i innovació en salut (PERIS)”. We thank CERCA Programme / Generalitat de Catalunya for institutional support. This project was funded by Instituto de Salud Carlos III (ISCIII), the Spanish Government Official Agency for funding biomedical research - with competitive grants leaded by Jordi Salas-Salvadó and Josep Vidal for the periods 2014 to 2020, through the Fondo de Investigación para la Salud (FIS), which is co-funded by the European Regional Development Fund, ERDF, a way to build Europe) [grants: PI13/00233, PI13/00728, PI13/01123, PI13/00462, PI16/00533, PI16/00366, PI16/01094, PI16/00501, PI17/01167, PI19/00017, PI19/00781, PI19/01032, PI19/00576]; the Especial Action Project entitled: Implementación y evaluación de una intervención intensiva sobre la actividad física Cohorte PREDIMED-Plus grant to Jordi Salas-Salvadó; the European Research Council [Advanced Research Grant 2014–2019; agreement #340918] granted to Miguel Ángel Martínez-González; the Recercaixa (number 2013ACUP00194) grant to Jordi Salas-Salvadó. This research was also partially funded by EU-H2020 Grants (Eat2beNICE/ H2020-SFS-2016-2; Ref 728018; and PRIME/ H2020-SC1-BHC-2018-2020; Ref: 847879), Grant PROMETEO/2017/017 (Generalitat Valenciana) and Grant FEA/SEA 2017 for Primary Care Research. This work is also partially supported by ICREA under the ICREA Academia programme. This work was supported by grants from DIUE de la Generalitat de Catalunya 2017 SGR 138 from the Departament d‟Economia i Coneixement de la Generalitat de Catalunya (Spain). Natalia Soldevila-Domenech is supported by the FI 2021 predoctoral grant (FI_B2021/00104) from the Agency for Management of University and Research Grants (AGAUR) of the Generalitat de Catalunya. This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CIBEROBN, CIBERER), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and European Union. None of these funding sources plays any role in the design, collection, analysis, or interpretation of the data or in the decision to submit manuscripts for publication. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.BioMed Central202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/60769http://dx.doi.org/10.1186/s12937-024-00966-wreponame:Repositorio Digital de la UPFinstname:Universitat Pompeu FabraInglésNutr J. 2024 Jun 12;23(1):61info:eu-repo/grantAgreement/EC/H2020/340918info:eu-repo/grantAgreement/EC/H2020/728018info:eu-repo/grantAgreement/EC/H2020/847879© The Author(s) 2024. 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The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:repositori.upf.edu:10230/607692026-06-12T07:21:37Z |
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