APOE-ε4 modulates the association between regional amyloid deposition and cognitive performance in cognitively unimpaired middle-aged individuals
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Published:2023-03-01
Issue:1
Volume:13
Page:
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ISSN:2191-219X
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Container-title:EJNMMI Research
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language:en
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Short-container-title:EJNMMI Res
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 DomingoORCID, Cañas Alba, Canals Lidia, Iglesias Laura, Marne Paula, Beteta Annabella, Deulofeu Carme, Emilio Maria, Cumplido Irene, Domínguez Ruth, Fuentes Sherezade, Hernández Laura, Vilanova Marc, Solsona Lluís, Huesa Gema, Huguet Jordi, Menchón Tania, Polo Albina, Pradas Sandra, Sala-Vila Aleix, Soteras Anna, Stankeviciute Laura, Akinci Müge, Palpatzis Eleni, Genius Patricia, Rodríguez Blanca, García Marina, Ortiz-Romero Paula,
Abstract
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.
Funder
Juan de la Cierva La Caixa Health Department of the Catalan Government Ministerio de Ciencia, Innovación y Universidades Alzheimer's Association Ramón y Cajal Spanish Ministry of Science and Innovation European Union’s Horizon 2020 Instituto de Salud Carlos III H2020 European Institute of Innovation and Technology
Publisher
Springer Science and Business Media LLC
Subject
Radiology, Nuclear Medicine and imaging
Reference43 articles.
1. Jack CR, Bennett DA, Blennow K, Carrillo MC, Feldman HH, Frisoni GB, et al. A/T/N: an unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016;87:539–47. 2. Morris JC. Early-stage and preclinical Alzheimer disease. Alzheimer Dis Assoc Disord. 2005;19:163–5. 3. Lim YY, Maruff P, Pietrzak RH, Ames D, Ellis KA, Harrington K, et al. Effect of amyloid on memory and non-memory decline from preclinical to clinical Alzheimer’s disease. Brain. 2014;137:221–31. 4. Harrington KD, Lim YY, Ames D, Hassenstab J, Laws SM, Martins RN, et al. Amyloid β-associated cognitive decline in the absence of clinical disease progression and systemic illness. Alzheimer’s Dement Diagn Assess Dis Monit. 2017;8:156–64. 5. Lim YY, Ellis KA, Pietrzak RH, Ames D, Darby D, Harrington K, et al. Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults. Neurology. 2012;79:1645–52.
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