Sex-specific protective effects of APOE ε2 on cognitive performance

Lamonja-Vicente, Noemí; Dacosta-Aguayo, Rosalia; López-Olóriz, Jorge; Prades-Senovilla, Laia; Roig-Coll, Francesca; Castells Sánchez, Alba; Soriano Raya, Juan José; Clemente, Immaculada; Miralbell Blanch, Júlia; Barrios Cerrejón, M. Teresa; López Cancio, Elena; Cáceres, Cynthia; Arenillas, Juan Francisco; Millán, Mónica; Torán Monserrat, Pere; Pera, Guillem; Forés, Rosa; Alzamora, María Teresa; Mataró Serrat, Maria; Via i García, Marc

Sex-specific protective effects of APOE ε2 on cognitive performance

Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships w...

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Autores:	Lamonja-Vicente, Noemí, Dacosta-Aguayo, Rosalia, López-Olóriz, Jorge, Prades-Senovilla, Laia, Roig-Coll, Francesca, Castells Sánchez, Alba, Soriano Raya, Juan José, Clemente, Immaculada, Miralbell Blanch, Júlia, Barrios Cerrejón, M. Teresa, López Cancio, Elena, Cáceres, Cynthia, Arenillas, Juan Francisco, Millán, Mónica, Torán Monserrat, Pere, Pera, Guillem, Forés, Rosa, Alzamora, María Teresa, Mataró Serrat, Maria, Via i García, Marc
Tipo de recurso:	artículo
Estado:	Versión aceptada para publicación
Fecha de publicación:	2021
País:	España
Institución:	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:	Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:	oai:recercat.cat:2445/219642
Acceso en línea:	https://hdl.handle.net/2445/219642
Access Level:	acceso abierto
Palabra clave:	Lípids Diferències entre sexes (Psicologia) Cognició Lipids Sex differences (Psychology) Cognition

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spelling	Sex-specific protective effects of APOE ε2 on cognitive performanceLamonja-Vicente, NoemíDacosta-Aguayo, RosaliaLópez-Olóriz, JorgePrades-Senovilla, LaiaRoig-Coll, FrancescaCastells Sánchez, AlbaSoriano Raya, Juan JoséClemente, ImmaculadaMiralbell Blanch, JúliaBarrios Cerrejón, M. TeresaLópez Cancio, ElenaCáceres, CynthiaArenillas, Juan FranciscoMillán, MónicaTorán Monserrat, PerePera, GuillemForés, RosaAlzamora, María TeresaMataró Serrat, MariaVia i García, MarcLípidsDiferències entre sexes (Psicologia)CognicióLipidsSex differences (Psychology)CognitionApolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (β = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and β = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.Gerontological Society of America2025202520212025info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersion35 p.application/pdfhttps://hdl.handle.net/2445/219642Articles publicats en revistes (Psicologia Social i Psicologia Quantitativa)reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésVersió postprint del document publicat a: https://doi.org/10.1093/gerona/glaa247Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 2021, vol. 76, num.1, p. 41-49https://doi.org/10.1093/gerona/glaa247(c) Lamonja, N. et al., 2021info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2196422026-05-29T05:05:01Z
dc.title.none.fl_str_mv	Sex-specific protective effects of APOE ε2 on cognitive performance
title	Sex-specific protective effects of APOE ε2 on cognitive performance
spellingShingle	Sex-specific protective effects of APOE ε2 on cognitive performance Lamonja-Vicente, Noemí Lípids Diferències entre sexes (Psicologia) Cognició Lipids Sex differences (Psychology) Cognition
title_short	Sex-specific protective effects of APOE ε2 on cognitive performance
title_full	Sex-specific protective effects of APOE ε2 on cognitive performance
title_fullStr	Sex-specific protective effects of APOE ε2 on cognitive performance
title_full_unstemmed	Sex-specific protective effects of APOE ε2 on cognitive performance
title_sort	Sex-specific protective effects of APOE ε2 on cognitive performance
dc.creator.none.fl_str_mv	Lamonja-Vicente, Noemí Dacosta-Aguayo, Rosalia López-Olóriz, Jorge Prades-Senovilla, Laia Roig-Coll, Francesca Castells Sánchez, Alba Soriano Raya, Juan José Clemente, Immaculada Miralbell Blanch, Júlia Barrios Cerrejón, M. Teresa López Cancio, Elena Cáceres, Cynthia Arenillas, Juan Francisco Millán, Mónica Torán Monserrat, Pere Pera, Guillem Forés, Rosa Alzamora, María Teresa Mataró Serrat, Maria Via i García, Marc
author	Lamonja-Vicente, Noemí
author_facet	Lamonja-Vicente, Noemí Dacosta-Aguayo, Rosalia López-Olóriz, Jorge Prades-Senovilla, Laia Roig-Coll, Francesca Castells Sánchez, Alba Soriano Raya, Juan José Clemente, Immaculada Miralbell Blanch, Júlia Barrios Cerrejón, M. Teresa López Cancio, Elena Cáceres, Cynthia Arenillas, Juan Francisco Millán, Mónica Torán Monserrat, Pere Pera, Guillem Forés, Rosa Alzamora, María Teresa Mataró Serrat, Maria Via i García, Marc
author_role	author
author2	Dacosta-Aguayo, Rosalia López-Olóriz, Jorge Prades-Senovilla, Laia Roig-Coll, Francesca Castells Sánchez, Alba Soriano Raya, Juan José Clemente, Immaculada Miralbell Blanch, Júlia Barrios Cerrejón, M. Teresa López Cancio, Elena Cáceres, Cynthia Arenillas, Juan Francisco Millán, Mónica Torán Monserrat, Pere Pera, Guillem Forés, Rosa Alzamora, María Teresa Mataró Serrat, Maria Via i García, Marc
author2_role	author author author author author author author author author author author author author author author author author author author
dc.subject.none.fl_str_mv	Lípids Diferències entre sexes (Psicologia) Cognició Lipids Sex differences (Psychology) Cognition
topic	Lípids Diferències entre sexes (Psicologia) Cognició Lipids Sex differences (Psychology) Cognition
description	Apolipoprotein E (APOE) has an important role in the multiple trajectories of cognitive aging. However, environmental variables and other genes mediate the impact of APOE on cognition. Our main objective was to analyze the effect of APOE genotype on cognition and its interactions and relationships with sex, age, lipid profile, C-reactive protein, and Brain-derived neurotrophic factor (BDNF) genotype in a sample of 648 healthy participants over 50 years of age with a comprehensive neuropsychological assessment. Our results showed that APOE ε2 carriers performed better in the Verbal Memory (p = .002) and Fluency Domains (p = .001). When we studied the effect of sex, we observed that the beneficial effect of APOE ε2 on the normalized values of these cognitive domains occurred only in females (β = 0.735; 95% confidence interval, 0.396-1.074; p = 3.167·10-5 and β = 0.568; 95% confidence interval, 0.276-0.861; p = 1.853·10-4, respectively). Similarly, the sex-specific effects of APOE ε2 were further observed on lipidic and inflammation biomarkers. In the whole sample, APOE ε2 carriers showed significantly lower levels of total cholesterol, low-density lipoprotein cholesterol, and C-reactive protein. These differences were found only among females. Furthermore, total cholesterol and low-density lipoprotein cholesterol mediated the protective effect of APOE ε2 on cognition in the whole sample and total cholesterol in females, providing candidate physiological mechanisms for the observed genetic effects. Our results show that the neuroprotective role of APOE ε2 in cognition varies with sex and that the lipidic profile partially mediates this protection. Age-related cognitive and functional decline is a continuous biological process with different cognitive trajectories (1). Complex interactions between heritability, environmental influence, and cognitive functions in aging have been highlighted (2). In particular, genetic differences explain around 15%-25% of the variance in life expectancy (3). Therefore, the identification of susceptibility genes and their biological effects on cognitive aging is required to establish interindividual differences in this process and promote early personalized interventions to delay cognitive decline and minimize the financial burden of aging in the health care system.
publishDate	2021
dc.date.none.fl_str_mv	2021 2025 2025 2025
dc.type.none.fl_str_mv	info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion
format	article
status_str	acceptedVersion
dc.identifier.none.fl_str_mv	https://hdl.handle.net/2445/219642
url	https://hdl.handle.net/2445/219642
dc.language.none.fl_str_mv	Inglés
language_invalid_str_mv	Inglés
dc.relation.none.fl_str_mv	Versió postprint del document publicat a: https://doi.org/10.1093/gerona/glaa247 Journals of Gerontology Series A: Biomedical Sciences and Medical Sciences, 2021, vol. 76, num.1, p. 41-49 https://doi.org/10.1093/gerona/glaa247
dc.rights.none.fl_str_mv	(c) Lamonja, N. et al., 2021 info:eu-repo/semantics/openAccess
rights_invalid_str_mv	(c) Lamonja, N. et al., 2021
eu_rights_str_mv	openAccess
dc.format.none.fl_str_mv	35 p. application/pdf
dc.publisher.none.fl_str_mv	Gerontological Society of America
publisher.none.fl_str_mv	Gerontological Society of America
dc.source.none.fl_str_mv	Articles publicats en revistes (Psicologia Social i Psicologia Quantitativa) reponame:Recercat. Dipósit de la Recerca de Catalunya instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str	Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str	Recercat. Dipósit de la Recerca de Catalunya
collection	Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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Sex-specific protective effects of APOE ε2 on cognitive performance

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