TY - JOUR
T1 - Age and diagnostic performance of Alzheimer disease CSF biomarkers
AU - Mattsson, N.
AU - Rosen, E.
AU - Hansson, O.
AU - Andreasen, N.
AU - Parnetti, L.
AU - Jonsson, M.
AU - Herukka, S. -K.
AU - van der Flier, W. M.
AU - Blankenstein, M. A.
AU - Ewers, M.
AU - Rich, K.
AU - Kaiser, E.
AU - Verbeek, M. M.
AU - Rikkert, M. Olde
AU - Tsolaki, M.
AU - Mulugeta, E.
AU - Aarsland, D.
AU - Visser, P. J.
AU - Schroeder, J.
AU - Marcusson, J.
AU - de Leon, M.
AU - Hampel, H.
AU - Scheltens, P.
AU - Wallin, A.
AU - Eriksdotter-Jonhagen, M.
AU - Minthon, L.
AU - Winblad, B.
AU - Blennow, K.
AU - Zetterberg, H.
PY - 2012/2
Y1 - 2012/2
N2 - 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
AB - 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
U2 - 10.1212/WNL.0b013e3182477eed
DO - 10.1212/WNL.0b013e3182477eed
M3 - Article
C2 - 22302554
SN - 0028-3878
VL - 78
SP - 468
EP - 476
JO - Neurology
JF - Neurology
IS - 7
ER -