APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals

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  • dc.contributor.author Brugulat Serrat, Anna, 1986-
  • dc.contributor.author Sánchez Benavides, Gonzalo
  • dc.contributor.author Cacciaglia, Raffaele
  • dc.contributor.author Shekari, Mahnaz
  • dc.contributor.author Milà Alomà, Marta
  • dc.contributor.author Vilor Tejedor, Natàlia, 1988-
  • dc.contributor.author Operto, Grégory
  • dc.contributor.author Falcón, Carles
  • dc.contributor.author Grau-Rivera, Oriol
  • dc.contributor.author Arenaza Urquijo, Eider M.
  • dc.contributor.author Minguillón, Carolina
  • dc.contributor.author Fauria, Karine
  • dc.contributor.author Suárez-Calvet, Marc
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author ALFA Study
  • dc.date.accessioned 2023-06-07T06:14:59Z
  • dc.date.available 2023-06-07T06:14:59Z
  • dc.date.issued 2023
  • dc.description.abstract Purpose: To determine whether the APOE-ε4 allele modulates the relationship between regional β-amyloid (Aβ) accumulation and cognitive change in middle-aged cognitively unimpaired (CU) participants. Methods: The 352 CU participants (mean aged 61.1 [4.7] years) included completed two cognitive assessments (average interval 3.34 years), underwent [18F]flutemetamol Aβ positron emission tomography (PET), T1w magnetic resonance imaging (MRI), as well as APOE genotyping. Global and regional Aβ PET positivity was assessed across five regions-of-interest by visual reading (VR) and regional Centiloids. Linear regression models were developed to examine the interaction between regional and global Aβ PET positivity and APOE-ε4 status on longitudinal cognitive change assessed with the Preclinical Alzheimer's Cognitive Composite (PACC), episodic memory, and executive function, after controlling for age, sex, education, cognitive baseline scores, and hippocampal volume. Results: In total, 57 participants (16.2%) were VR+ of whom 41 (71.9%) were APOE-ε4 carriers. No significant APOE-ε4*global Aβ PET interactions were associated with cognitive change for any cognitive test. However, APOE-ε4 carriers who were VR+ in temporal areas (n = 19 [9.81%], p = 0.04) and in the striatum (n = 8 [4.14%], p = 0.01) exhibited a higher decline in the PACC. The temporal areas findings were replicated when regional PET positivity was determined with Centiloid values. Regionally, VR+ in the striatum was associated with higher memory decline. As for executive function, interactions between APOE-ε4 and regional VR+ were found in temporal and parietal regions, and in the striatum. Conclusion: CU APOE-ε4 carriers with a positive Aβ PET VR in regions known to accumulate amyloid at later stages of the Alzheimer's disease (AD) continuum exhibited a steeper cognitive decline. This work supports the contention that regional VR of Aβ PET might convey prognostic information about future cognitive decline in individuals at higher risk of developing AD. Clinicaltrials: gov Identifier: NCT02485730. Registered 20 June 2015 https://clinicaltrials.gov/ct2/show/NCT02485730 and ClinicalTrials.gov Identifier:NCT02685969. Registered 19 February 2016 https://clinicaltrials.gov/ct2/show/NCT02685969 .
  • dc.description.sponsorship The research leading to these results has received funding from “la Caixa” Foundation (LCF/PR/GN17/10300004) 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 under grant 2021 SGR 00913. NV-T is funded by a postdoctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministry of Science and Innovation-Spanish State Research Agency. Her research has received additional support of “la Caixa” Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan 2016–2020 Grant SLT002/16/00201). OG-R is supported by the Spanish Ministry of Science, Innovation and Universities (IJC2020-043417-I) and receives funding from the Alzheimer’s Association Research Fellowship Program (2019-AARF-644568). EA-U is supported by Alzheimer’s Association research grants (AARG 2019-AARG-644641, AARG 2019-AARG-644641-RAPID), a “Ramón y Cajal” fellowship (RYC2018-026053-I) and by a grant of the Ministry of Science and Innovation (PID2019-111514RA-I00). MS-C receives funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (Grant agreement No. 948677), the Instituto de Salud Carlos III (PI19/00155), and from a fellowship from “la Caixa” Foundation (ID 100010434) and from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847648 (LCF/BQ/PR21/11840004). JD-G holds a “Ramón y Cajal” fellowship (RYC-2013-13054).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Brugulat-Serrat A, Sánchez-Benavides G, Cacciaglia R, Salvadó G, Shekari M, Collij LE, et al. APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals. EJNMMI Res. 2023 Mar 1;13(1):18. DOI: 10.1186/s13550-023-00967-6
  • dc.identifier.doi http://dx.doi.org/10.1186/s13550-023-00967-6
  • dc.identifier.issn 2191-219X
  • dc.identifier.uri http://hdl.handle.net/10230/57086
  • dc.language.iso eng
  • dc.publisher Springer
  • dc.relation.ispartof EJNMMI Res. 2023 Mar 1;13(1):18
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/948677
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-111514RA-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/847648
  • dc.rights © The Author(s) 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword APOE-ε4
  • dc.subject.keyword Alzheimer’s disease
  • dc.subject.keyword Amyloid PET
  • dc.subject.keyword Executive function
  • dc.subject.keyword Memory
  • dc.subject.keyword Visual read
  • dc.title APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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