Prevalence and prognosis of Alzheimer’s disease at the mild cognitive impairment stage

• Published in: Brain (London, England : 1878) Vol. 138; no. 5; pp. 1327 - 1338
• Main Authors: Vos, Stephanie J. B., Verhey, Frans, Frölich, Lutz, Kornhuber, Johannes, Wiltfang, Jens, Maier, Wolfgang, Peters, Oliver, Rüther, Eckart, Nobili, Flavio, Morbelli, Silvia, Frisoni, Giovanni B., Drzezga, Alexander, Didic, Mira, van Berckel, Bart N. M., Simmons, Andrew, Soininen, Hilkka, Kłoszewska, Iwona, Mecocci, Patrizia, Tsolaki, Magda, Vellas, Bruno, Lovestone, Simon, Muscio, Cristina, Herukka, Sanna-Kaisa, Salmon, Eric, Bastin, Christine, Wallin, Anders, Nordlund, Arto, de Mendonça, Alexandre, Silva, Dina, Santana, Isabel, Lemos, Raquel, Engelborghs, Sebastiaan, Van der Mussele, Stefan, Freund-Levi, Yvonne, Wallin, Åsa K., Hampel, Harald, van der Flier, Wiesje, Scheltens, Philip, Visser, Pieter Jelle
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2015
• Subjects: Adult; Aged; Aged, 80 and over; Alzheimer Disease - complications; Alzheimer Disease - epidemiology; Alzheimer’s disease; Biomarkers; Biomarkers - metabolism; Clinical Medicine; Cognitive Dysfunction - epidemiology; Cognitive Dysfunction - etiology; Diagnostic criteria; Disease Progression; Female; Humans; Klinisk medicin; Male; MCI; Medical and Health Sciences; Medicin och hälsovetenskap; Middle Aged; Neurologi; Neurology; Neuropsychological Tests; Original; Prevalence; Prognosis; Survival Analysis; MCI; diagnostic criteria; Alzheimer’s disease; prognosis; biomarkers
• ISSN: 0006-8950; 1460-2156; 1460-2156
• DOI: 10.1093/brain/awv029

© The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com Three sets of research criteria are available for diagnosis of Alzheimer's disease in subjects with mild cognitive impairment: the International Working Group-1, International Working Group-2, and National Institute of Aging-Alzheimer Association criteria. We compared the prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage according to these criteria. Subjects with mild cognitive impairment (n = 1607), 766 of whom had both amyloid and neuronal injury markers, were recruited from 13 cohorts. We used cognitive test performance and available biomarkers to classify subjects as prodromal Alzheimer's disease according to International Working Group-1 and International Working Group-2 criteria and in the high Alzheimer's disease likelihood group, conflicting biomarker groups (isolated amyloid pathology or suspected non-Alzheimer pathophysiology), and low Alzheimer's disease likelihood group according to the National Institute of Ageing-Alzheimer Association criteria. Outcome measures were the proportion of subjects with Alzheimer's disease at the mild cognitive impairment stage and progression to Alzheimer's disease-type dementia. We performed survival analyses using Cox proportional hazards models. According to the International Working Group-1 criteria, 850 (53%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 50% compared to 21% for subjects without prodromal Alzheimer's disease. According to the International Working Group-2 criteria, 308 (40%) subjects had prodromal Alzheimer's disease. Their 3-year progression rate to Alzheimer's disease-type dementia was 61% compared to 22% for subjects without prodromal Alzheimer's disease. According to the National Institute of Ageing-Alzheimer Association criteria, 353 (46%) subjects were in the high Alzheimer's disease likelihood group, 49 (6%) in the isolated amyloid pathology group, 220 (29%) in the suspected non-Alzheimer pathophysiology group, and 144 (19%) in the low Alzheimer's disease likelihood group. The 3-year progression rate to Alzheimer's disease-type dementia was 59% in the high Alzheimer's disease likelihood group, 22% in the isolated amyloid pathology group, 24% in the suspected non-Alzheimer pathophysiology group, and 5% in the low Alzheimer's disease likelihood group. Our findings support the use of the proposed research criteria to identify Alzheimer's disease at the mild cognitive impairment stage. In clinical settings, the use of both amyloid and neuronal injury markers as proposed by the National Institute of Ageing-Alzheimer Association criteria offers the most accurate prognosis. For clinical trials, selection of subjects in the National Institute of Ageing-Alzheimer Association high Alzheimer's disease likelihood group or the International Working Group-2 prodromal Alzheimer's disease group could be considered. This study resulted from a collaboration between centers of the European Alzheimer's Disease Consortium (EADC). The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under EMIF grant agreement n° 115372, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies’ in kind contribution. This research was performed within the framework of CTMM, The Centre for Translational Molecular Medicine (www.ctmm.nl), project LeARN (grant 02N-101). The DESCRIPA study was funded by the European Commission within the 5th framework program (QLRT-2001- 2455). The AddNeuroMed study was funded by InnoMed (Innovative Medicines in Europe), an Integrated Project funded by the European Union of the Sixth Framework program priority FP6-2004-LIFESCIHEALTH-5, Life Sciences, Genomics and Biotechnology for Health. The Coimbra Centre was funded by Project PIC/IC/ 83206/2007 da Fundação para a Ciência e Tecnologia – Portugal. Research of the VUmc Alzheimer centre is part of the neurodegeneration research program of the Neuroscience Campus Amsterdam. The VUmc Alzheimer Centre is supported by Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. The Alzheimer's Disease Neuroimaging Initiative (ADNI; National Institutes of Health Grant U01 AG024904 and DOD ADNI Department of Defense award number W81XWH-12-2-0012) was funded by the National Institute on Aging, the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Alzheimer’s Association; Alzheimer’s Drug Discovery Foundation; BioClinica, Inc.; Biogen Idec Inc.; Bristol-Myers Squibb Company; Eisai Inc.; Elan Pharmaceuticals, Inc.; Eli Lilly and Company; F. Hoffmann-La Roche Ltd and its affiliated company Genentech, Inc.; GE Healthcare; Innogenetics, N.V.; IXICO Ltd.; Janssen Alzheimer Immunotherapy Research & Development, LLC.; Johnson & Johnson Pharmaceutical Research & Development LLC.; Medpace, Inc.; Merck & Co., Inc.; Meso Scale Diagnostics, LLC.; NeuroRx Research; Novartis Pharmaceuticals Corporation; Pfizer Inc.; Piramal Imaging; Servier; Synarc Inc.; and Takeda Pharmaceutical Company. The Canadian Institutes of Health Research is providing funds to Rev December 5, 2013 support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer's Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory for Neuro Imaging at the University of Southern California.