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

来源：

NEUROLOGY | 2012年 / 78卷 / 07期

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

页码：468 / 476

页数：9

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