Amyloid-PET imaging predicts functional decline in clinically normal individuals

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  • dc.contributor.author Quenon, Lisa
  • dc.contributor.author Gispert López, Juan Domingo
  • dc.contributor.author Shekari, Mahnaz
  • dc.contributor.author AMYPAD Consortium
  • dc.date.accessioned 2025-02-18T06:17:12Z
  • dc.date.available 2025-02-18T06:17:12Z
  • dc.date.issued 2024
  • dc.description.abstract Background: There is good evidence that elevated amyloid-β (Aβ) positron emission tomography (PET) signal is associated with cognitive decline in clinically normal (CN) individuals. However, it is less well established whether there is an association between the Aβ burden and decline in daily living activities in this population. Moreover, Aβ-PET Centiloids (CL) thresholds that can optimally predict functional decline have not yet been established. Methods: Cross-sectional and longitudinal analyses over a mean three-year timeframe were performed on the European amyloid-PET imaging AMYPAD-PNHS dataset that phenotypes 1260 individuals, including 1032 CN individuals and 228 participants with questionable functional impairment. Amyloid-PET was assessed continuously on the Centiloid (CL) scale and using Aβ groups (CL < 12 = Aβ-, 12 ≤ CL ≤ 50 = Aβ-intermediate/Aβ± , CL > 50 = Aβ+). Functional abilities were longitudinally assessed using the Clinical Dementia Rating (Global-CDR, CDR-SOB) and the Amsterdam Instrumental Activities of Daily Living Questionnaire (A-IADL-Q). The Global-CDR was available for the 1260 participants at baseline, while baseline CDR-SOB and A-IADL-Q scores and longitudinal functional data were available for different subsamples that had similar characteristics to those of the entire sample. Results: Participants included 765 Aβ- (61%, Mdnage = 66.0, IQRage = 61.0-71.0; 59% women), 301 Aβ± (24%; Mdnage = 69.0, IQRage = 64.0-75.0; 53% women) and 194 Aβ+ individuals (15%, Mdnage = 73.0, IQRage = 68.0-78.0; 53% women). Cross-sectionally, CL values were associated with CDR outcomes. Longitudinally, baseline CL values predicted prospective changes in the CDR-SOB (bCL*Time = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (bCL*Time = -0.010/CL/year, 95% CI [-0.016,-0.004], p = .002) scores in initially CN participants. Increased clinical progression (Global-CDR > 0) was mainly observed in Aβ+ CN individuals (HRAβ+ vs Aβ- = 2.55, 95% CI [1.16,5.60], p = .020). Optimal thresholds for predicting decline were found at 41 CL using the CDR-SOB (bAβ+ vs Aβ- = 0.137/year, 95% CI [0.069,0.206], p < .001) and 28 CL using the A-IADL-Q (bAβ+ vs Aβ- = -0.693/year, 95% CI [-1.179,-0.208], p = .005). Conclusions: Amyloid-PET quantification supports the identification of CN individuals at risk of functional decline. Trial registration: The AMYPAD PNHS is registered at www.clinicaltrialsregister.eu with the EudraCT Number: 2018-002277-22.
  • dc.description.sponsorship This work used data from AMYPAD PNHS and received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115952. This Joint Undertaking received support from the European Union’s Horizon 2020 research and innovation programme and EFPIA (http://www.imi.europa.eu). BH received grants from the Belgian Foundation for Scientific Research (FNRS CCL grant #40010417; WELBIO fund #40010035), the Belgian Alzheimer Research Foundation (SAO-FRA:2022/0026), the Helaers Foundation, and the Queen Elizabeth Medical Foundation (QEMF-FMRE).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Quenon L, Collij LE, Garcia DV, Lopes Alves I, Gérard T, Malotaux V, et al. Amyloid-PET imaging predicts functional decline in clinically normal individuals. Alzheimers Res Ther. 2024 Jun 17;16(1):130. DOI: 10.1186/s13195-024-01494-9
  • dc.identifier.doi http://dx.doi.org/10.1186/s13195-024-01494-9
  • dc.identifier.issn 1758-9193
  • dc.identifier.uri http://hdl.handle.net/10230/69624
  • dc.language.iso eng
  • dc.publisher BioMed Central
  • dc.relation.ispartof Alzheimers Res Ther. 2024 Jun 17;16(1):130
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/115952
  • dc.rights © The Author(s) 2024. Open Access 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/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.title Amyloid-PET imaging predicts functional decline in clinically normal individuals
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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