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@ARTICLE{Quenon:270307,
      author       = {Quenon, Lisa and Collij, Lyduine E and Garcia, David
                      Vállez and Lopes Alves, Isadora and Gérard, Thomas and
                      Malotaux, Vincent and Huyghe, Lara and Gispert, Juan Domingo
                      and Jessen, Frank and Visser, Pieter Jelle and den Braber,
                      Anouk and Ritchie, Craig W and Boada, Mercè and Marquié,
                      Marta and Vandenberghe, Rik and Luckett, Emma S and Schöll,
                      Michael and Frisoni, Giovanni B and Buckley, Christopher and
                      Stephens, Andrew and Altomare, Daniele and Ford, Lisa and
                      Birck, Cindy and Mett, Anja and Gismondi, Rossella and Wolz,
                      Robin and Grootoonk, Sylke and Manber, Richard and Shekari,
                      Mahnaz and Lhommel, Renaud and Dricot, Laurence and Ivanoiu,
                      Adrian and Farrar, Gill and Barkhof, Frederik and Hanseeuw,
                      Bernard J},
      collaboration = {Consortium, AMYPAD},
      title        = {{A}myloid-{PET} imaging predicts functional decline in
                      clinically normal individuals.},
      journal      = {Alzheimer's research $\&$ therapy},
      volume       = {16},
      number       = {1},
      issn         = {1758-9193},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DZNE-2024-00779},
      pages        = {130},
      year         = {2024},
      abstract     = {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.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.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).Amyloid-PET quantification supports the identification
                      of CN individuals at risk of functional decline.The AMYPAD
                      PNHS is registered at www.clinicaltrialsregister.eu with the
                      EudraCT Number: 2018-002277-22.},
      keywords     = {Humans / Positron-Emission Tomography: methods / Female /
                      Male / Cross-Sectional Studies / Longitudinal Studies / Aged
                      / Amyloid beta-Peptides: metabolism / Activities of Daily
                      Living / Cognitive Dysfunction: diagnostic imaging /
                      Cognitive Dysfunction: metabolism / Middle Aged / Brain:
                      diagnostic imaging / Brain: metabolism / Aged, 80 and over /
                      Amyloid-PET (Other) / Centiloid (Other) / Functional decline
                      (Other) / Instrumental activities of daily living (Other) /
                      Preclinical Alzheimer (Other) / Amyloid beta-Peptides (NLM
                      Chemicals)},
      cin          = {AG Jessen},
      ddc          = {610},
      cid          = {I:(DE-2719)1011102},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC11181677},
      pubmed       = {pmid:38886831},
      doi          = {10.1186/s13195-024-01494-9},
      url          = {https://pub.dzne.de/record/270307},
}