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...
| Autores: | , , , , , , , , , , , , , , , , , , , |
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| Formato: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2021 |
| País: | España |
| Recursos: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/219642 |
| Acesso em linha: | https://hdl.handle.net/2445/219642 |
| Access Level: | acceso abierto |
| Palavra-chave: | Lípids Diferències entre sexes (Psicologia) Cognició Lipids Sex differences (Psychology) Cognition |
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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 America2021info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionapplication/pdfhttps://hdl.handle.net/2445/219642Articles publicats en revistes (Psicologia Social i Psicologia Quantitativa)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésVersió 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:diposit.ub.edu:2445/2196422026-05-27T06:46:51Z |
| 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 |
| 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 |
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(c) Lamonja, N. et al., 2021 |
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openAccess |
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application/pdf |
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Gerontological Society of America |
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Gerontological Society of America |
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Articles publicats en revistes (Psicologia Social i Psicologia Quantitativa) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
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Dipòsit Digital de la UB |
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