Prognostic value of Alzheimer’s biomarkers in mild cognitive impairment: the effect of age at onset

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Objective: The aim of this study is to assess the impact of age at onset on the prognostic value of Alzheimer’s biomarkers in a large sample of patients with mild cognitive impairment (MCI). Methods: We measured Aβ42, t-tau, hippocampal volume on magnetic resonance imaging (MRI) and cortical metabolism on fluorodeoxyglucose–positron emission tomography (FDG-PET) in 188 MCI patients followed for at least 1 year. We categorised patients into earlier and later onset (EO/LO). Receiver operating characteristic curves and corresponding areas under the curve (AUCs) were performed to assess and compar the biomarker prognostic performances in EO and LO groups. Linear Model was adopted for estimating the time-to-progression in relation with earlier/later onset MCI groups and biomarkers. Results: In earlier onset patients, all the assessed biomarkers were able to predict cognitive decline (p < 0.05), with FDG-PET showing the best performance. In later onset patients, all biomarkers but t-tau predicted cognitive decline (p < 0.05). Moreover, FDG-PET alone in earlier onset patients showed a higher prognostic value than the one resulting from the combination of all the biomarkers in later onset patients (earlier onset AUC 0.935 vs later onset AUC 0.753, p < 0.001). Finally, FDG-PET showed a different prognostic value between earlier and later onset patients (p = 0.040) in time-to-progression allowing an estimate of the time free from disease. Discussion: FDG-PET may represent the most universal tool for the establishment of a prognosis in MCI patients and may be used for obtaining an onset-related estimate of the time free from disease.


  • for the Alzheimer’s Disease Neuroimaging Initiative
  • Daniele Altomare
  • Clarissa Ferrari
  • Anna Caroli
  • Samantha Galluzzi
  • Annapaola Prestia
  • Wiesje M. van der Flier
  • Rik Ossenkoppele
  • Bart Van Berckel
  • Frederik Barkhof
  • Charlotte E. Teunissen
  • Anders Wall
  • Stephen F. Carter
  • Michael Schöll
  • Il Han Choo
  • Timo Grimmer
  • Alberto Redolfi
  • Agneta Nordberg
  • Philip Scheltens
  • Alexander Drzezga
  • Giovanni B Frisoni
External organisations
  • Geneva University Hospital
  • Centro San Giovanni di Dio Fatebenefratelli
  • Amsterdam UMC - Vrije Universiteit Amsterdam
  • University College London
  • Uppsala University
  • Karolinska Institutet
  • University of Manchester
  • Klinikum rechts der Isar
  • Karolinska University Hospital
  • University of Cologne
  • Mario Negri Institute for Pharmacological Research
  • Vrije Universiteit Amsterdam
  • University of Gothenburg
  • Chosun University
  • Technical University of Munich
  • University of Geneva
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology


  • Alzheimer, Biomarkers, Cognition, FDG-PET, Imaging
Original languageEnglish
JournalJournal of Neurology
Publication statusE-pub ahead of print - 2019 Jul 2
Publication categoryResearch