Age and diagnostic performance of Alzheimer disease CSF biomarkers

Research output: Contribution to journalArticle

Abstract

Objectives: Core CSF changes in Alzheimer disease (AD) are decreased amyloid beta(1-42), increased total tau, and increased phospho-tau, probably indicating amyloid plaque accumulation, axonal degeneration, and tangle pathology, respectively. These biomarkers identify AD already at the predementia stage, but their diagnostic performance might be affected by age-dependent increase of AD-type brain pathology in cognitively unaffected elderly. Methods: We investigated effects of age on the diagnostic performance of CSF biomarkers in a uniquely large multicenter study population, including a cross-sectional cohort of 529 patients with AD dementia (median age 71, range 43-89 years) and 304 controls (67, 44-91 years), and a longitudinal cohort of 750 subjects without dementia with mild cognitive impairment (69, 43-89 years) followed for at least 2 years, or until dementia diagnosis. Results: The specificities for subjects without AD and the areas under the receiver operating characteristics curves decreased with age. However, the positive predictive value for a combination of biomarkers remained stable, while the negative predictive value decreased only slightly in old subjects, as an effect of the high AD prevalence in older ages. Conclusion: Although the diagnostic accuracies for AD decreased with age, the predictive values for a combination of biomarkers remained essentially stable. The findings highlight biomarker variability across ages, but support the use of CSF biomarkers for AD even in older populations. Neurology (R) 2012;78:468-476

Details

Authors
  • N. Mattsson
  • E. Rosen
  • N. Andreasen
  • L. Parnetti
  • M. Jonsson
  • S. -K. Herukka
  • W. M. van der Flier
  • M. A. Blankenstein
  • M. Ewers
  • K. Rich
  • E. Kaiser
  • M. M. Verbeek
  • M. Olde Rikkert
  • M. Tsolaki
  • E. Mulugeta
  • D. Aarsland
  • P. J. Visser
  • J. Schroeder
  • J. Marcusson
  • M. de Leon
  • H. Hampel
  • P. Scheltens
  • A. Wallin
  • M. Eriksdotter-Jonhagen
  • B. Winblad
  • K. Blennow
  • H. Zetterberg
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Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurology
Original languageEnglish
Pages (from-to)468-476
JournalNeurology
Volume78
Issue number7
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes