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Brain. 2015 May;138(Pt 5):1327-38. doi: 10.1093/brain/awv029. Epub 2015 Feb 17.

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

Author information

  • 11 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands s.vos@maastrichtuniversity.nl.
  • 21 Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Centre Limburg, Maastricht, The Netherlands.
  • 32 Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit, University of Heidelberg, Mannheim, Germany.
  • 43 Department of Psychiatry and Psychotherapy, Friedrich-Alexander University of Erlangen, Erlangen, Germany.
  • 54 Department of Psychiatry and Psychotherapy, University Medical Centre (UMG), Georg-August-University, Göttingen, Germany.
  • 65 Department of Psychiatry and Psychotherapy, University of Bonn, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany.
  • 76 Department of Psychiatry and Psychotherapy, Charité Berlin, Berlin, Germany.
  • 87 Department of Psychiatry and Psychotherapy, University of Göttingen, Göttingen, Germany.
  • 98 Clinical Neurophysiology Service, Department of Neurosciences, Ophthalmology and Genetics, University of Genoa, Genoa, Italy.
  • 109 Nuclear Medicine, Department of Internal Medicine, University of Genoa, Genoa, Italy.
  • 1110 IRCCS San Giovanni di Dio Fatebenefratelli, Brescia, Italy 11 University Hospitals and University of Geneva, Geneva, Switzerland.
  • 1212 Department of Nuclear Medicine, University of Cologne, Cologne, Germany.
  • 1313 Service de Neurologie et Neuropsychologie, Pôle de neurosciences cliniques, AP-HM Timone, Aix Marseille Université, INS UMR_S 1106, 13005, Marseille, France.
  • 1414 Department of Nuclear Medicine and PET Research, VU University Medical CentRE, Amsterdam, The Netherlands.
  • 1515 Department of Neuroimaging, Centre for Neuroimaging Science, King's College London, Institute of Psychiatry, London, UK.
  • 1616 Institute of Clinical Medicine, Neurology, University of Eastern Finland and Neurocenter, Neurology, Kuopio University Hospital, Kuopio, Finland.
  • 1717 Medical University of Lodz, Lodz, Poland.
  • 1818 Institute of Gerontology and Geriatrics, University of Perugia, Perugia, Italy.
  • 1919 Aristotle University of Thessaloniki, Memory and Dementia Center, 3rd Department of Neurology, "G Papanicolaou" General Hospital, Thessaloniki, Greece.
  • 2020 UMR INSERM 1027, CHU Toulouse, Toulouse, France.
  • 2121 University of Oxford, Department of Psychiatry, Oxford, UK.
  • 2210 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.
  • 2324 Memory Clinic, Department of Neurology, CHU Liège, Belgium 25 Cyclotron Research Centre, University of Liège, Liège, Belgium.
  • 2425 Cyclotron Research Centre, University of Liège, Liège, Belgium.
  • 2526 Department of Psychiatry and Neurochemistry, Institute for Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
  • 2627 Institute of Molecular Medicine, Faculty of Medicine, University of Lisbon, Portugal.
  • 2728 Department of Neurology, Coimbra University Hospital, Coimbra, Portugal.
  • 2829 Faculty of Psychology and Educational Sciences, University of Coimbra, Coimbra, Portugal.
  • 2930 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.
  • 3030 Reference Centre for Biological Markers of Dementia (BIODEM), Laboratory of Neurochemistry and Behaviour, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
  • 3132 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.
  • 3233 Lund University, Clinical Sciences Malmö, Clinical Memory Research Unit, Lund, Sweden.
  • 3334 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.
  • 3435 Alzheimer Centre and Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
  • 351 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.

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.

© 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.

KEYWORDS:

Alzheimer’s disease; MCI; biomarkers; diagnostic criteria; prognosis

PMID:
25693589
[PubMed - indexed for MEDLINE]
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