Age and diagnostic performance of Alzheimer disease CSF biomarkers

被引:129
作者
Mattsson, N. [1 ]
Rosen, E. [1 ]
Hansson, O. [2 ]
Andreasen, N. [3 ]
Parnetti, L. [4 ]
Jonsson, M. [1 ]
Herukka, S. -K. [5 ,6 ]
van der Flier, W. M. [7 ,8 ]
Blankenstein, M. A. [7 ,8 ]
Ewers, M. [10 ,11 ]
Rich, K. [12 ]
Kaiser, E. [14 ]
Verbeek, M. M. [15 ,16 ]
Rikkert, M. Olde [15 ,16 ]
Tsolaki, M. [17 ]
Mulugeta, E. [19 ]
Aarsland, D. [20 ]
Visser, P. J. [18 ]
Schroeder, J. [14 ]
Marcusson, J. [13 ]
de Leon, M. [12 ]
Hampel, H. [9 ]
Scheltens, P. [7 ,8 ]
Wallin, A. [1 ]
Eriksdotter-Jonhagen, M. [3 ]
Minthon, L. [2 ]
Winblad, B. [3 ]
Blennow, K. [1 ]
Zetterberg, H. [1 ]
机构
[1] Univ Gothenburg, Sahlgrenska Acad, Dept Neurochem & Psychiat, Inst Neurosci & Physiol,Clin Neurochem Lab, Molndal, Sweden
[2] Lund Univ, Clin Memory Res Unit, Lund, Sweden
[3] Karolinska Univ Hosp, Stockholm, Sweden
[4] Univ Perugia, Clin Neurol, I-06100 Perugia, Italy
[5] Univ Eastern Finland, Clin Res Ctr Mediteknia, Dept Neurol, Kuopio, Finland
[6] Univ Eastern Finland, Clin Res Ctr Mediteknia, Brain Res Unit, Kuopio, Finland
[7] Vrije Univ Amsterdam Med Ctr, Dept Neurol, Amsterdam, Netherlands
[8] Vrije Univ Amsterdam Med Ctr, Alzheimer Ctr, Amsterdam, Netherlands
[9] Goethe Univ Frankfurt, Dept Psychiat Psychosomat Med & Psychotherapy, Frankfurt, Germany
[10] Univ Calif San Francisco, Ctr Neuroimaging Neurodegenerat Dis, Dept Radiol, San Francisco, CA 94143 USA
[11] Univ Calif San Francisco, Ctr Neuroimaging Neurodegenerat Dis, VA Med Ctr, San Francisco, CA 94143 USA
[12] NYU, Sch Med, Ctr Brain Hlth, New York, NY USA
[13] Linkoping Univ, Div Geriatr Med, Dept Clin & Expt Med, Linkoping, Sweden
[14] Heidelberg Univ, Sekt Gerontopsychiat, Heidelberg, Germany
[15] Radboud Univ Nijmegen Med Ctr, Alzheimer Ctr Nijmegen, Donders Inst Brain Cognit & Behav, Dept Neurol, Nijmegen, Netherlands
[16] Radboud Univ Nijmegen Med Ctr, Alzheimer Ctr Nijmegen, Donders Inst Brain Cognit & Behav, Lab Med, Nijmegen, Netherlands
[17] Aristotle Univ Thessaloniki, G Papanicolaou Gen Hosp, Dept Neurol 3, Memory & Dementia Ctr, GR-54006 Thessaloniki, Greece
[18] Univ Maastricht, Inst Brain & Behav, Dept Psychiat & Neuropsychol, Maastricht, Netherlands
[19] Kings Coll London, Wolfson Ctr Age Related Dis, London WC2R 2LS, England
[20] Stavanger Univ Hosp, Ctr Age Related Med, Stavanger, Norway
基金
瑞典研究理事会;
关键词
MILD COGNITIVE IMPAIRMENT; CEREBROSPINAL-FLUID; ASSOCIATION WORKGROUPS; PHOSPHORYLATED-TAU; NATIONAL INSTITUTE; BIOCHEMICAL MARKER; DEMENTIA; NEUROPATHOLOGY; BETA-AMYLOID((1-42)); RECOMMENDATIONS;
D O I
10.1212/WNL.0b013e3182477eed
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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
引用
收藏
页码:468 / 476
页数:9
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