APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals
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 assess...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Berlin Heidelberg
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978048/ https://www.ncbi.nlm.nih.gov/pubmed/36856866 http://dx.doi.org/10.1186/s13550-023-00967-6 |
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author | Brugulat-Serrat, Anna Sánchez-Benavides, Gonzalo Cacciaglia, Raffaele Salvadó, Gemma Shekari, Mahnaz Collij, Lyduine E. Buckley, Christopher van Berckel, Bart N. M. Perissinotti, Andrés Niñerola-Baizán, Aida Milà-Alomà, Marta Vilor-Tejedor, Natàlia Operto, Grégory Falcon, Carles Grau-Rivera, Oriol Arenaza-Urquijo, Eider M. Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Suárez-Calvet, Marc Gispert, Juan Domingo |
author_facet | Brugulat-Serrat, Anna Sánchez-Benavides, Gonzalo Cacciaglia, Raffaele Salvadó, Gemma Shekari, Mahnaz Collij, Lyduine E. Buckley, Christopher van Berckel, Bart N. M. Perissinotti, Andrés Niñerola-Baizán, Aida Milà-Alomà, Marta Vilor-Tejedor, Natàlia Operto, Grégory Falcon, Carles Grau-Rivera, Oriol Arenaza-Urquijo, Eider M. Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Suárez-Calvet, Marc Gispert, Juan Domingo |
author_sort | Brugulat-Serrat, Anna |
collection | PubMed |
description | 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 [(18)F]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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-023-00967-6. |
format | Online Article Text |
id | pubmed-9978048 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-99780482023-03-03 APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals Brugulat-Serrat, Anna Sánchez-Benavides, Gonzalo Cacciaglia, Raffaele Salvadó, Gemma Shekari, Mahnaz Collij, Lyduine E. Buckley, Christopher van Berckel, Bart N. M. Perissinotti, Andrés Niñerola-Baizán, Aida Milà-Alomà, Marta Vilor-Tejedor, Natàlia Operto, Grégory Falcon, Carles Grau-Rivera, Oriol Arenaza-Urquijo, Eider M. Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Suárez-Calvet, Marc Gispert, Juan Domingo EJNMMI Res Original Research 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 [(18)F]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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13550-023-00967-6. Springer Berlin Heidelberg 2023-03-01 /pmc/articles/PMC9978048/ /pubmed/36856866 http://dx.doi.org/10.1186/s13550-023-00967-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Research Brugulat-Serrat, Anna Sánchez-Benavides, Gonzalo Cacciaglia, Raffaele Salvadó, Gemma Shekari, Mahnaz Collij, Lyduine E. Buckley, Christopher van Berckel, Bart N. M. Perissinotti, Andrés Niñerola-Baizán, Aida Milà-Alomà, Marta Vilor-Tejedor, Natàlia Operto, Grégory Falcon, Carles Grau-Rivera, Oriol Arenaza-Urquijo, Eider M. Minguillón, Carolina Fauria, Karine Molinuevo, José Luis Suárez-Calvet, Marc Gispert, Juan Domingo APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title | APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title_full | APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title_fullStr | APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title_full_unstemmed | APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title_short | APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
title_sort | apoe-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9978048/ https://www.ncbi.nlm.nih.gov/pubmed/36856866 http://dx.doi.org/10.1186/s13550-023-00967-6 |
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