Unbiased estimates of cerebrospinal fluid β-amyloid 1-42 cutoffs in a large memory clinic population

被引:64
作者
Bertens, Daniela [1 ,2 ]
Tijms, Betty M. [1 ,2 ]
Scheltens, Philip [1 ,2 ]
Teunissen, Charlotte E. [3 ,4 ]
Visser, Pieter Jelle [1 ,2 ,5 ]
机构
[1] Vrije Univ Amsterdam, Dept Neurol, Med Ctr, Neurosci Campus Amsterdam, Amsterdam, Netherlands
[2] Vrije Univ Amsterdam, Med Ctr, Alzheimer Ctr, Neurosci Campus Amsterdam,De Boelelaan 1118, NL-1081 HZ Amsterdam, Netherlands
[3] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Neurochem Lab, Neurosci Campus Amsterdam, Amsterdam, Netherlands
[4] Vrije Univ Amsterdam, Med Ctr, Dept Clin Chem, Biobank, Neurosci Campus Amsterdam, Amsterdam, Netherlands
[5] Univ Med Ctr Maastricht, Alzheimer Ctr, Sch Mental Hlth & Neurosci MHeNS, Maastricht, Netherlands
关键词
Alzheimer's disease; MCI; Cerebrospinal fluid; Diagnosis; MILD COGNITIVE IMPAIRMENT; ALZHEIMERS ASSOCIATION WORKGROUPS; PROGRESSIVE SUPRANUCLEAR PALSY; DIAGNOSTIC-CRITERIA; FRONTOTEMPORAL DEMENTIA; INTERNATIONAL WORKSHOP; NATIONAL INSTITUTE; DISEASE; BIOMARKERS; PET;
D O I
10.1186/s13195-016-0233-7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: We sought to define a cutoff for beta-amyloid 1-42 in cerebrospinal fluid (CSF), a key marker for Alzheimer's disease (AD), with data-driven Gaussian mixture modeling in a memory clinic population. Methods: We performed a combined cross-sectional and prospective cohort study. We selected 2462 subjects with subjective cognitive decline, mild cognitive impairment, AD-type dementia, and dementia other than AD from the Amsterdam Dementia Cohort. We defined CSF beta-amyloid 1-42 cutoffs by data-driven Gaussian mixture modeling in the total population and in subgroups based on clinical diagnosis, age, and apolipoprotein E (APOE) genotype. We investigated whether abnormal beta-amyloid 1-42 as defined by the data-driven cutoff could better predict progression to AD-type dementia than abnormal beta-amyloid 1-42 defined by a clinical diagnosis-based cutoff using Cox proportional hazards regression. Results: In the total group of patients, we found a cutoff for abnormal CSF beta-amyloid 1-42 of 680 pg/ml (95% CI 660-705 pg/ml). Similar cutoffs were found within diagnostic and APOE genotype subgroups. The cutoff was higher in elderly subjects than in younger subjects. The data-driven cutoff was higher than our clinical diagnosisbased cutoff and had a better predictive accuracy for progression to AD-type dementia in nondemented subjects (HR 7.6 versus 5.2, p < 0.01). Conclusions: Mixture modeling is a robust method to determine cutoffs for CSF beta-amyloid 1-42. It might better capture biological changes that are related to AD than cutoffs based on clinical diagnosis.
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页数:8
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共 31 条
[1]   The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease [J].
Albert, Marilyn S. ;
DeKosky, Steven T. ;
Dickson, Dennis ;
Dubois, Bruno ;
Feldman, Howard H. ;
Fox, Nick C. ;
Gamst, Anthony ;
Holtzman, David M. ;
Jagust, William J. ;
Petersen, Ronald C. ;
Snyder, Peter J. ;
Carrillo, Maria C. ;
Thies, Bill ;
Phelps, Creighton H. .
ALZHEIMERS & DEMENTIA, 2011, 7 (03) :270-279
[2]  
Bartlett JW, 2012, BIOMARK MED, V6, P391, DOI [10.2217/bmm.12.49, 10.2217/BMM.12.49]
[3]   The use of biomarkers for the etiologic diagnosis of MCI in Europe: An EADC survey [J].
Bocchetta, Martina ;
Galluzzi, Samantha ;
Kehoe, Patrick Gavin ;
Aguera, Eduardo ;
Bernabei, Roberto ;
Bullock, Roger ;
Ceccaldi, Mathieu ;
Dartigues, Jean-Francois ;
de Mendonca, Alexandre ;
Didic, Mira ;
Eriksdotter, Maria ;
Felician, Olivier ;
Froelich, Lutz ;
Gertz, Hermann-Josef ;
Hallikainen, Merja ;
Hasselbalch, Steen G. ;
Hausner, Lucrezia ;
Heuser, Isabell ;
Jessen, Frank ;
Jones, Roy W. ;
Kurz, Alexander ;
Lawlor, Brian ;
Lleo, Alberto ;
Martinez-Lage, Pablo ;
Mecocci, Patrizia ;
Mehrabian, Shima ;
Monsch, Andreas ;
Nobili, Flavio ;
Nordberg, Agneta ;
Rikkert, Marcel Olde ;
Orgogozo, Jean-Marc ;
Pasquier, Florence ;
Peters, Oliver ;
Salmon, Eric ;
Sanchez-Castellano, Carmen ;
Santana, Isabel ;
Sarazin, Marie ;
Traykov, Latchezar ;
Tsolaki, Magda ;
Visser, Pieter Jelle ;
Wallin, Asa K. ;
Wilcock, Gordon ;
Wilkinson, David ;
Wolf, Henrike ;
Yener, Goersev ;
Zekry, Dina ;
Frisoni, Giovanni B. .
ALZHEIMERS & DEMENTIA, 2015, 11 (02) :195-206
[4]   Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia [J].
Boeve, BF ;
Lang, AE ;
Litvan, I .
ANNALS OF NEUROLOGY, 2003, 54 :S15-S19
[5]  
Clark CM, 2012, LANCET NEUROL, V11, P669, DOI 10.1016/S1474-4422(12)70142-4
[6]   Diagnosis-Independent Alzheimer Disease Biomarker Signature in Cognitively Normal Elderly People [J].
De Meyer, Geert ;
Shapiro, Fred ;
Vanderstichele, Hugo ;
Vanmechelen, Eugeen ;
Engelborghs, Sebastiaan ;
De Deyn, Peter Paul ;
Coart, Els ;
Hansson, Oskar ;
Minthon, Lennart ;
Zetterberg, Henrik ;
Blennow, Kaj ;
Shaw, Leslie ;
Trojanowski, John Q. .
ARCHIVES OF NEUROLOGY, 2010, 67 (08) :949-956
[7]   Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria [J].
Dubois, Bruno ;
Feldman, Howard H. ;
Jacova, Claudia ;
Hampel, Harald ;
Molinuevo, Jose Luis ;
Blennow, Kaj ;
Dekosky, Steven T. ;
Gauthier, Serge ;
Selkoe, Dennis ;
Bateman, Randall ;
Cappa, Stefano ;
Crutch, Sebastian ;
Engelborghs, Sebastiaan ;
Frisoni, Giovanni B. ;
Fox, Nick C. ;
Galasko, Douglas ;
Habert, Marie-Odile ;
Jicha, Gregory A. ;
Nordberg, Agneta ;
Pasquier, Florence ;
Rabinovici, Gil ;
Robert, Philippe ;
Rowe, Christopher ;
Salloway, Stephen ;
Sarazin, Marie ;
Epelbaum, Stephane ;
de Souza, Leonardo C. ;
Vellas, Bruno ;
Visser, Pieter J. ;
Schneider, Lon ;
Stern, Yaakov ;
Scheltens, Philip ;
Cummings, Jeffrey L. .
LANCET NEUROLOGY, 2014, 13 (06) :614-629
[8]   Prevalence of Cerebral Amyloid Pathology in Persons Without Dementia A Meta-analysis [J].
Jansen, Willemijn J. ;
Ossenkoppele, Rik ;
Knol, Dirk L. ;
Tijms, Betty M. ;
Scheltens, Philip ;
Verhey, Frans R. J. ;
Visser, Pieter Jelle .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2015, 313 (19) :1924-1938
[9]   A conceptual framework for research on subjective cognitive decline in preclinical Alzheimer's disease [J].
Jessen, Frank ;
Amariglio, Rebecca E. ;
van Boxtel, Martin ;
Breteler, Monique ;
Ceccaldi, Mathieu ;
Chetelat, Gael ;
Dubois, Bruno ;
Dufouil, Carole ;
Ellis, Kathryn A. ;
van der Flier, Wiesje M. ;
Glodzik, Lidia ;
van Harten, Argonde C. ;
de Leon, Mony J. ;
McHugh, Pauline ;
Mielke, Michelle M. ;
Molinuevo, Jose Luis ;
Mosconi, Lisa ;
Osorio, Ricardo S. ;
Perrotin, Audrey ;
Petersen, Ronald C. ;
Rabin, Laura A. ;
Rami, Lorena ;
Reisberg, Barry ;
Rentz, Dorene M. ;
Sachdev, Perminder S. ;
de la Sayette, Vincent ;
Saykin, Andrew J. ;
Scheltens, Philip ;
Shulman, Melanie B. ;
Slavin, Melissa J. ;
Sperling, Reisa A. ;
Stewart, Robert ;
Uspenskaya, Olga ;
Vellas, Bruno ;
Visser, Pieter Jelle ;
Wagner, Michael .
ALZHEIMERS & DEMENTIA, 2014, 10 (06) :844-852
[10]   Apolipoprotein E Genotype and the Diagnostic Accuracy of Cerebrospinal Fluid Biomarkers for Alzheimer Disease [J].
Lautner, Ronald ;
Palmqvist, Sebastian ;
Mattsson, Niklas ;
Andreasson, Ulf ;
Wallin, Anders ;
Palsson, Erik ;
Jakobsson, Joel ;
Herukka, Sanna-Kaisa ;
Owenius, Rikard ;
Olsson, Bob ;
Hampel, Harald ;
Rujescu, Dan ;
Ewers, Michael ;
Landen, Mikael ;
Minthon, Lennart ;
Blennow, Kaj ;
Zetterberg, Henrik ;
Hansson, Oskar .
JAMA PSYCHIATRY, 2014, 71 (10) :1183-1191