DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease

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• dc.contributor.author Sala Vila, Aleix
• dc.contributor.author Arenaza Urquijo, Eider M.
• dc.contributor.author Sánchez Benavides, Gonzalo
• dc.contributor.author Suárez-Calvet, Marc
• dc.contributor.author Milà Alomà, Marta
• dc.contributor.author Grau-Rivera, Oriol
• dc.contributor.author González de Echávarri, José Maria
• dc.contributor.author Crous-Bou, Marta
• dc.contributor.author Minguillón, Carolina
• dc.contributor.author Fauria, Karine
• dc.contributor.author Operto, Grégory
• dc.contributor.author Falcón, Carles
• dc.contributor.author Salvadó, Gemma
• dc.contributor.author Cacciaglia, Raffaele
• dc.contributor.author Ingala, Silvia
• dc.contributor.author Barkhof, Frederik
• dc.contributor.author Schröder, Helmut, 1958-
• dc.contributor.author Scarmeas, Nikolaos
• dc.contributor.author Gispert López, Juan Domingo
• dc.contributor.author Molinuevo, José Luis
• dc.contributor.author ALFA Study
• dc.date.accessioned 2021-04-19T07:33:02Z
• dc.date.available 2021-04-19T07:33:02Z
• dc.date.issued 2021
• dc.description.abstract Background: The number of APOE-ε4 alleles is a major nonmodifiable risk factor for sporadic Alzheimer disease (AD). There is increasing evidence on the benefits of dietary DHA (22:6n-3) before the onset of AD symptoms, particularly in APOE-ε4 carriers. Brain alterations in the preclinical stage can be detected by structural MRI. Objectives: We aimed, in middle-aged cognitively unimpaired individuals at increased risk of AD, to cross-sectionally investigate whether dietary DHA intake relates to cognitive performance and to MRI-based markers of cerebral small vessel disease and AD-related neurodegeneration, exploring the effect modification by APOE-ε4 status. Methods: In 340 participants of the ALFA (ALzheimer and FAmilies) study, which is enriched for APOE-ε4 carriership (n = 122, noncarriers; n = 157, 1 allele; n = 61, 2 alleles), we assessed self-reported DHA intake through an FFQ. We measured cognitive performance by administering episodic memory and executive function tests. We performed high-resolution structural MRI to assess cerebral small vessel disease [white matter hyperintensities (WMHs) and cerebral microbleeds (CMBs)] and AD-related brain atrophy (cortical thickness in an AD signature). We constructed regression models adjusted for potential confounders, exploring the interaction DHA × APOE-ε4. Results: We observed no significant associations between DHA and cognitive performance or WMH burden. We observed a nonsignificant inverse association between DHA and prevalence of lobar CMBs (OR: 0.446; 95% CI: 0.195, 1.018; P = 0.055). DHA was found to be significantly related to greater cortical thickness in the AD signature in homozygotes but not in nonhomozygotes (P-interaction = 0.045). The association strengthened when analyzing homozygotes and nonhomozygotes matched for risk factors. Conclusions: In cognitively unimpaired APOE-ε4 homozygotes, dietary DHA intake related to structural patterns that may result in greater resilience to AD pathology. This is consistent with the current hypothesis that those subjects at highest risk would obtain the largest benefits from DHA supplementation in the preclinical stage.This trial was registered at clinicaltrials.gov as NCT01835717.
• dc.description.sponsorship Supported by “la Caixa” Foundation (ID 100010434) under agreement LCF/PR/GN17/10300004 (to JLM). In addition, supported by Universities and Research Secretariat, Ministry of Business and Knowledge of the Catalan Government grant no. 2017-SGR-892 (to JLM). AS-V is the recipient of Instituto de Salud Carlos III Miguel Servet fellowship grant CP II 17/00029. EMA-U is the recipient of Alzheimer's Association research grant AARG 2019-AARG-644641 and holds “Ramón y Cajal” fellowship RYC2018-026053-I. MS-C received funding from the European Union's Horizon 2020 Research and Innovation Program under Marie Sklodowska-Curie action grant agreement no. 752310 and is currently supported by Instituto de Salud Carlos III grant PI19/00155 and Spanish Ministry of Science, Innovation, and Universities Juan de la Cierva Programme grant IJC2018-037478-I. FB is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. JD-G holds “Ramón y Cajal” fellowship RYC-2013-13054.
• dc.format.mimetype application/pdf
• dc.identifier.citation Sala-Vila A, Arenaza-Urquijo EM, Sánchez-Benavides G, Suárez-Calvet M, Milà-Alomà M, Grau-Rivera O et al. DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease. Am J Clin Nutr. 2021 Mar 18:nqab016. DOI: 10.1093/ajcn/nqab016
• dc.identifier.doi http://dx.doi.org/10.1093/ajcn/nqab016
• dc.identifier.issn 0002-9165
• dc.identifier.uri http://hdl.handle.net/10230/47147
• dc.language.iso eng
• dc.publisher American Society for Nutrition
• dc.relation.ispartof Am J Clin Nutr. 2021 Mar 18:nqab016
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/752310
• dc.rights © The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
• dc.subject.keyword Brain atrophy
• dc.subject.keyword Cerebral small vessel disease
• dc.subject.keyword Cognition
• dc.subject.keyword Markers
• dc.subject.keyword Omega-3 fatty acids
• dc.subject.keyword White matter hyperintensities
• dc.title DHA intake relates to better cerebrovascular and neurodegeneration neuroimaging phenotypes in middle-aged adults at increased genetic risk of Alzheimer disease
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion