e-Article
Amyloid-PET imaging predicts functional decline in clinically normal individuals
Document Type
article
Author
Lisa Quenon; Lyduine E. Collij; David Vállez Garcia; Isadora Lopes Alves; Thomas Gérard; Vincent Malotaux; Lara Huyghe; Juan Domingo Gispert; Frank Jessen; Pieter Jelle Visser; Anouk den Braber; Craig W. Ritchie; Mercè Boada; Marta Marquié; Rik Vandenberghe; Emma S. Luckett; Michael Schöll; Giovanni B. Frisoni; Christopher Buckley; Andrew Stephens; Daniele Altomare; Lisa Ford; Cindy Birck; Anja Mett; Rossella Gismondi; Robin Wolz; Sylke Grootoonk; Richard Manber; Mahnaz Shekari; Renaud Lhommel; Laurence Dricot; Adrian Ivanoiu; Gill Farrar; Frederik Barkhof; Bernard J. Hanseeuw; the AMYPAD Consortium
Source
Alzheimer’s Research & Therapy, Vol 16, Iss 1, Pp 1-13 (2024)
Subject
Language
English
ISSN
1758-9193
Abstract
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 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%, Mdn age = 66.0, IQR age = 61.0–71.0; 59% women), 301 Aβ± (24%; Mdn age = 69.0, IQR age = 64.0–75.0; 53% women) and 194 Aβ+ individuals (15%, Mdn age = 73.0, IQR age = 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 (b CL*Time = 0.001/CL/year, 95% CI [0.0005,0.0024], p = .003) and A-IADL-Q (b CL*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 (HR Aβ+ 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 (b Aβ+ vs Aβ- = 0.137/year, 95% CI [0.069,0.206], p