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Age and diagnostic performance of Alzheimer disease CSF biomarkers

Mattsson, N.; Rosen, E.; Hansson, Oskar LU ; Andreasen, N.; Parnetti, L.; Jonsson, M.; Herukka, S. -K.; van der Flier, W. M.; Blankenstein, M. A. and Ewers, M., et al. (2012) In Neurology 78(7). p.468-476
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... (More)
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 (Less)
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Contribution to journal
publication status
published
subject
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Neurology
volume
78
issue
7
pages
468 - 476
publisher
American Academy of Neurology
external identifiers
  • wos:000300605100008
  • scopus:84858113047
ISSN
1526-632X
DOI
10.1212/WNL.0b013e3182477eed
language
English
LU publication?
yes
id
cd6944d1-a9b7-4b96-a10e-822d79204470 (old id 2403121)
date added to LUP
2012-04-02 09:27:16
date last changed
2017-09-24 03:52:32
@article{cd6944d1-a9b7-4b96-a10e-822d79204470,
  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},
  author       = {Mattsson, N. and Rosen, E. and Hansson, Oskar and Andreasen, N. and Parnetti, L. and Jonsson, M. and Herukka, S. -K. and van der Flier, W. M. and Blankenstein, M. A. and Ewers, M. and Rich, K. and Kaiser, E. and Verbeek, M. M. and Rikkert, M. Olde and Tsolaki, M. and Mulugeta, E. and Aarsland, D. and Visser, P. J. and Schroeder, J. and Marcusson, J. and de Leon, M. and Hampel, H. and Scheltens, P. and Wallin, A. and Eriksdotter-Jonhagen, M. and Minthon, Lennart and Winblad, B. and Blennow, K. and Zetterberg, H.},
  issn         = {1526-632X},
  language     = {eng},
  number       = {7},
  pages        = {468--476},
  publisher    = {American Academy of Neurology},
  series       = {Neurology},
  title        = {Age and diagnostic performance of Alzheimer disease CSF biomarkers},
  url          = {http://dx.doi.org/10.1212/WNL.0b013e3182477eed},
  volume       = {78},
  year         = {2012},
}