title: Prevalence and prognosis of Alzheimer's disease at the mild cognitive impairment stage.
abstract: 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.
authors.affiliation: 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands s.vos@maastrichtuniversity.nl.
authors.forename: Stephanie J B
authors.initials: SJ
authors.lastname: Vos
authors.affiliation: 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands.
authors.forename: Frans
authors.initials: F
authors.lastname: Verhey
authors.affiliation: 2 Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Frölich
authors.affiliation: 3 Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen, Erlangen, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Kornhuber
authors.affiliation: 4 Department of Psychiatry and Psychotherapy, University Medical Centre (UMG), Georg-August-University, Göttingen, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Wiltfang
authors.affiliation: 5 Department of Psychiatry and Psychotherapy, University of Bonn, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.affiliation: 6 Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Peters
authors.affiliation: 7 Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
authors.forename: Eckart
authors.initials: E
authors.lastname: Rüther
authors.affiliation: 8 Clinical Neurophysiology Service, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
authors.forename: Flavio
authors.initials: F
authors.lastname: Nobili
authors.affiliation: 9 Nuclear Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Morbelli
authors.affiliation: 10 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy 11 University Hospitals and University of Geneva, Geneva, Switzerland.
authors.forename: Giovanni B
authors.initials: GB
authors.lastname: Frisoni
authors.affiliation: 12 Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Drzezga
authors.affiliation: 13 Service de Neurologie et Neuropsychologie, Pôle de neurosciences cliniques, AP-HM Timone, Aix Marseille Université, INS UMR_S 1106, 13005, Marseille, France.
authors.forename: Mira
authors.initials: M
authors.lastname: Didic
authors.affiliation: 14 Department of Nuclear Medicine and PET Research, VU University Medical CentRE, Amsterdam, The Netherlands.
authors.forename: Bart N M
authors.initials: BN
authors.lastname: van Berckel
authors.affiliation: 15 Department of Neuroimaging, Centre for Neuroimaging Science, King's College London, Institute of Psychiatry, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Simmons
authors.affiliation: 16 Institute of Clinical Medicine, Neurology, University of Eastern Finland and Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Hilkka
authors.initials: H
authors.lastname: Soininen
authors.affiliation: 17 Medical University of Lodz, Lodz, Poland.
authors.forename: Iwona
authors.initials: I
authors.lastname: Kłoszewska
authors.affiliation: 18 Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mecocci
authors.affiliation: 19 Aristotle University of Thessaloniki, Memory and Dementia Center, 3rd Department of Neurology, "G Papanicolaou" General Hospital, Thessaloniki, Greece.
authors.forename: Magda
authors.initials: M
authors.lastname: Tsolaki
authors.affiliation: 20 UMR INSERM 1027, CHU Toulouse, Toulouse, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vellas
authors.affiliation: 21 University of Oxford, Department of Psychiatry, Oxford, UK.
authors.forename: Simon
authors.initials: S
authors.lastname: Lovestone
authors.affiliation: 10 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy 22 Fondazione Europea Ricerca Biomedica (FERB), Centro di Eccellenza Alzheimer, Ospedale Briolini, Gazzaniga, Bergamo, Italy 23 Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Muscio
authors.affiliation: 16 Institute of Clinical Medicine, Neurology, University of Eastern Finland and Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Sanna-Kaisa
authors.initials: SK
authors.lastname: Herukka
authors.affiliation: 24 Memory Clinic, Department of Neurology, CHU Liège, Belgium 25 Cyclotron Research Centre, University of Liège, Liège, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Salmon
authors.affiliation: 25 Cyclotron Research Centre, University of Liège, Liège, Belgium.
authors.forename: Christine
authors.initials: C
authors.lastname: Bastin
authors.affiliation: 26 Department of Psychiatry and Neurochemistry, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Wallin
authors.affiliation: 26 Department of Psychiatry and Neurochemistry, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Arto
authors.initials: A
authors.lastname: Nordlund
authors.affiliation: 27 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: Alexandre
authors.initials: A
authors.lastname: de Mendonça
authors.affiliation: 27 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal.
authors.forename: Dina
authors.initials: D
authors.lastname: Silva
authors.affiliation: 28 Department of Neurology, Coimbra University Hospital, Coimbra, Portugal.
authors.forename: Isabel
authors.initials: I
authors.lastname: Santana
authors.affiliation: 29 Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal.
authors.forename: Raquel
authors.initials: R
authors.lastname: Lemos
authors.affiliation: 30 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium 31 Department of Neurology and Memory Clinic, Hospital Network Antwerp, Middelheim and Hoge Beuken, Antwerp, Belgium.
authors.forename: Sebastiaan
authors.initials: S
authors.lastname: Engelborghs
authors.affiliation: 30 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Van der Mussele
authors.affiliation: 32 Department of Neurobiology, Caring Sciences and Society (NVS), Division of Clinical Geriatrics, Karolinska Institutet, and Department of Geriatric Medicine, Karolinska University Hospital Huddinge, Stockholm, Sweden.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Freund-Levi
authors.affiliation: 33 Lund University, Clinical Sciences Malmö, Clinical Memory Research Unit, Lund, Sweden.
authors.forename: Åsa K
authors.initials: ÅK
authors.lastname: Wallin
authors.affiliation: 34 Centre des Maladies Cognitives et Comportementales, Institut du Cerveau et de la Moelle épinière, Paris, France; Université Pierre et Marie Curie-Paris 6, AP-HP, Hôpital de la Salpêtrière, Paris, France.
authors.forename: Harald
authors.initials: H
authors.lastname: Hampel
authors.affiliation: 35 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Wiesje
authors.initials: W
authors.lastname: van der Flier
authors.affiliation: 35 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: 1 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands 35 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications / Q000453:epidemiology*; D015415:Biomarkers / Q000378:metabolism; D060825:Cognitive Dysfunction / Q000453:epidemiology* / Q000209:etiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D015995:Prevalence; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015415:Biomarkers
keywords: Alzheimer’s disease; MCI; biomarkers; diagnostic criteria; prognosis